tbuckley/cabot-search huggingface dataset:
AB0589 The role of anca specificity in the clinical manifestations at disease onset: comparison between patients with granulomatosis with polyangiitis and microscopic polyangiitis
Authors: S Monti, M Felicetti, S Balduzzi, R Padoan, A Berti, G Paolazzi, G Brunori, F Schiavon, R Caporali
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> ANCA specificity, rather than clinical diagnosis, has been suggested to influence the phenotype and clinical course of ANCA associated vasculitis (AAV) (1,2). <h3>Objectives</h3> To investigate differences in clinical presentation at disease onset between MPO-ANCA-positive granulomatosis with polyangiitis patients (MPO-GPA), PR3-ANCA-positive-GPA (PR3-GPA), and MPO-ANCA-positive microscopic polyangiitis (MPO-MPA). <h3>Methods</h3> Clinical records of AAV patients from three third level rheumatologic centers in Northern Italy were retrospectively analyzed. <h3>Results</h3> Of the 133 AAV patients included, 84 were PR3-GPA, 24 MPO-GPA, and 25 MPO-MPA. Patients with MPO-MPA were significantly older at diagnosis compared to both PR3-GPA and MPO-GPA (average age 63±10, 49±15, 55±29, respectively) (Table 1). Patients with MPO-GPA experienced a significant diagnostic delay compared to PR3-GPA (17±30 vs 7±14, p=0.02). ENT involvement was equally frequent in both GPA groups despite ANCA specificity, and significantly more represented than the MPO-MPA group (68%, 71% and 17% respectively; p&lt;0.001). Figure 1. Renal involvement was significantly more frequent in MPO-MPA patients (100%) compared to GPA (p&lt;0.001), without differences between MPO-GPA (46%) and PR3-GPA (65%). Alveolar haemorrhage (DAH) was an onset manifestation mainly in MPO-MPA compared to the other two groups (24% vs 7% in PR3-GPA; p=0.02). Cutenous manifestations, mainly purpura, were significantly more reported in PR3-GPA compared to MPO-MPA (29% vs 4%; p=0.03). <h3>Conclusions</h3> Clinical phenotype of GPA at disease onset did not seem to be influenced by ANCA specificity. Despite ANCA positivity (PR3 or MPO), GPA patients were significantly different from MPA. <h3>References</h3> Schirmer JH, Wright MN, Herrmann K, et al. Myeloperoxidase-Antineutrophil Cytoplasmic Antibody (ANCA)-Positive Granulomatosis With Polyangiitis (Wegener9s) Is a Clinically Distinct Subset of ANCA-Associated Vasculitis: A Retrospective Analysis of 315 Patients From a German Vasculitis Referral Center. Arthritis Rheumatol Hoboken NJ 2016;68:2953–63. Miloslavsky EM, Lu N, Unizony S, et al. Myeloperoxidase-Antineutrophil Cytoplasmic Antibody (ANCA)-Positive and ANCA-Negative Patients With Granulomatosis With Polyangiitis (Wegener9s): Distinct Patient Subsets. Arthritis Rheumatol 2016;68:2945–2952. <h3>Disclosure of Interest</h3> None declared
AB0130 Mesenchymal stem cells alleviate sle through promoting treg cells by hla-g
Authors: C Chen, J Liang, G Yao, Z Zhang, S Huang, L Sun
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Soluble human leukocyte antigen-G (sHLA-G) is a non-classical HLA class I molecule, exhibiting strong immunosuppressive properties by inducing the differentiation of T regulatory cells (Treg). Mesenchymal stem cells (MSCs) transplantation alleviates disease progression in systemic lupus erythematosus (SLE) patients. However, the underlying mechanisms are largely unknown. <h3>Objectives</h3> The aim of the present study is to explore whether sHLA-G is involved in upregulating Treg cells by MSCs, which contributes to therapeutic effects of MSCs transplantation in SLE. <h3>Methods</h3> The serum sHLA-G levels of SLE patients and healthy controls were detected by ELISA. The percentages of peripheral blood CD4 + ILT2 +, CD8 + ILT2 +, CD19 + ILT2 + cells and Treg cells were determined by flow cytometry. Ten patients with active SLE, refractory to conventional therapies, were infused with MSCs and serum sHLA-G was measured 24 h after infusion. Peripheral blood mononuclear cells (PBMCs) were isolated from SLE patients and co-cultured with UC-MSCs for 3 days at different ratios (50:1, 10:1, and 2:1) with or without anti-HLA-G antibodies, and the frequencies of CD4 + CD25 + Foxp3 + T cells were then determined by flow cytometry. <h3>Results</h3> The concentrations of serum sHLA-G were comparable between SLE patients and healthy controls. However, there was a negative correlation between sHLA-G levels and SLE disease activity index (SLEDAI) scores in active SLE patients (SLEDAI &gt;4). We found that serum sHLA-G levels were negatively correlated with blood urea nitrogen, serum creatinine and 24-hour urine protein in SLE patients. The sHLA-G levels were significantly lower in SLE patients with renal involvement than those without renal involvement. The expression of ILT2 on CD4 + T cells from SLE patients decreased significantly compared to that of healthy controls. A positive correlation between the frequencies of Treg and CD4 + ILT2 + T cells was found in SLE patients. The levels of sHLA-G increased 24 h after UC-MSC transplantation. The frequencies of Treg cells and the expressions of ILT2 on CD4 + Tcells were significantly increased 24 h after transplantations. <i>In vitro</i> studies showed that MSCs increased the frequency of Treg cells in SLE patients in a dose-dependent manner, which was partly abrogated by the anti-HLA-G antibody. <h3>Conclusions</h3> Our results suggested that MSCs might alleviate SLE through upregulating Treg cells, which was partly dependent on sHLA-G. <h3>Disclosure of Interest</h3> None declared
A randomized phase II trial of CRLX101 in combination with bevacizumab versus standard of care in patients with advanced renal cell carcinoma
Authors: M.H. Voss, A. Hussain, N. Vogelzang, J.L. Lee, B. Keam, S.Y. Rha, U. Vaishampayan, W.B. Harris, S. Richey, J.M. Randall, D. Shaffer, A. Cohn, T. Crowell, J. Li, A. Senderowicz, E. Stone, R. Figlin, R.J. Motzer, N.B. Haas, T. Hutson
Journal: Annals of Oncology (2017)
SAT0740-HPR Significant others as both barriers and facilitators for participation in daily activities in persons with early rheumatoid arthritis – an interview study within the swedish tira project
Authors: M Bergström, A Sverker, Å Larsson Ranada, E Valtersson, I Thyberg, G Östlund, M Björk
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Restrictions in participation in persons with rheumatoid arthritis (RA) have been reported to be closely connected with more pain, fatigue and difficulties in performing daily activities. In addition, support and positive interactions with others have been considered important. We therefore need to understand how significant others of persons with RA can be facilitators or barriers, in participation in daily activities. This becomes of even greater importance in the sensitive and adapting phase of early RA. <h3>Objectives</h3> To describe the meaning of significant others in relation to participation in daily activities in persons with early RA. <h3>Methods</h3> This interview study is part of the multicenter project TIRA. Fifty-nine persons (58% women) participated. Inclusion criteria were a diagnosis of RA during three years and being in working age, &lt;64 years of age. Semi-structured interviews were conducted using Critical Incidence Technique (CIT) [1] and the material was analyzed using content analysis [2]. The study was approved by the Regional Ethics Committee. <h3>Results</h3> Four categories were revealed: <i>(1) Feelings and thoughts related to significant others</i>, where participants would feel like being someone9s burden, taking out aggression on others, and express anxiety about how relationships and activities would function in the future. <i>(2) The importance of physical contact</i>, referring to both the problematic and manageable impact RA could have on intimate life, as well as body contact in the form of hugging. <i>(3) Getting the support you want</i>, where participants distinguished getting help they had not asked for, from helping each other out. The first being experienced as degrading, and the latter as feeling more involved in the activity. <i>(4) Adaption of daily activities</i>, referring to how the person and significant others consciously modified their activities and activity choices when needed. <h3>Conclusions</h3> Significant others can be either a barrier or facilitator for participation in daily activities, for persons with early RA. From a clinical point of view it is important to further involve significant others in the rehabilitation process, in order to enhance participation in daily activities for persons with RA. <h3>References</h3> Flanagan, C. The critical incidence technique. Psychol Bull 1954;51(4):327–58. Graneheim, UH. &amp; Lundman, B. Qualitative content analysis in nursing research: concepts, procedures and measures to achieve trustworthiness. Nurse Educ Today 2004;24(2): 105–12. <h3>Disclosure of Interest</h3> None declared
Pooled Analysis Safety Profile of Nivolumab and Ipilimumab Combination Therapy in Patients With Advanced Melanoma
Authors: Mario Sznol, Pier Francesco Ferrucci, David Hogg, Michael B. Atkins, Pascal Wolter, Massimo Guidoboni, Celeste Lebbé, John M. Kirkwood, Jacob Schachter, Gregory A. Daniels, Jessica Hassel, Jonathan Cebon, Winald Gerritsen, Victoria Atkinson, Luc Thomas, John McCaffrey, Derek Power, Dana Walker, Rafia Bhore, Joel Jiang, F. Stephen Hodi, Jedd D. Wolchok
Journal: Journal of Clinical Oncology (2017)

Purpose The addition of nivolumab (anti-programmed death-1 antibody) to ipilimumab (anti-cytotoxic T-cell lymphocyte-associated 4 antibody) in patients with advanced melanoma improves antitumor response and progression-free survival but with a higher frequency of adverse events (AEs). This cross-melanoma study describes the safety profile of the approved nivolumab plus ipilimumab regimen. Methods This retrospective safety review on data from three trials (phase I, II, and III) included patients with advanced melanoma who received at least one dose of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks × 4 and then nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity while following established guidelines for AE management. Analyses were of all treatment-related AEs, select (immune-related) AEs, time to onset and resolution, and use of immune-modulating agents and their effects on outcome. Results Among 448 patients, median duration of follow-up was 13.2 months. Treatment-related grade 3/4 AEs occurred in 55.5% of patients; 35.7% had treatment-related AEs that led to discontinuation. The most frequent treatment-related select AEs of any grade were skin (64.3%) and GI (46.7%) and of grade 3/4, hepatic (17.0%) and GI (16.3%); 30.1% developed a grade 2 to 4 select AE in more than one organ category. Median time to onset of grade 3/4 treatment-related select AEs ranged from 3.1 (skin) to 16.3 (renal) weeks, and with the exclusion of endocrine AEs, median time to resolution from onset ranged from 1.9 (renal) to 4.5 (pulmonary) weeks, with resolution rates between 79% and 100% while using immune-modulating agents. Four (< 1%) on-study deaths were attributed to therapy. Conclusion Frequency of grade 3/4 treatment-related AEs was higher with nivolumab plus ipilimumab and occurred earlier than historical experience with either agent alone, but resolution rates were similar.
Tumor Resection Recruits Effector T Cells and Boosts Therapeutic Efficacy of Encapsulated Stem Cells Expressing IFNβ in Glioblastomas
Authors: Sung Hugh Choi, Daniel W. Stuckey, Sara Pignatta, Clemens Reinshagen, Jasneet Kaur Khalsa, Nicolaas Roozendaal, Jordi Martinez-Quintanilla, Kaoru Tamura, Erhan Keles, Khalid Shah
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Despite tumor resection being the first-line clinical care for glioblastoma (GBM) patients, nearly all preclinical immune therapy models intend to treat established GBM. Characterizing cytoreductive surgery-induced immune response combined with the administration of immune cytokines has the potential of offering a new treatment paradigm of immune therapy for GBMs. Experimental Design: We developed syngeneic orthotopic mouse GBM models of tumor resection and characterized the immune response of intact and resected tumors. We also created a highly secretable variant of immune cytokine IFNβ to enhance its release from engineered mouse mesenchymal stem cells (MSC-IFNβ) and assessed whether surgical resection of intracranial GBM tumor significantly enhanced the antitumor efficacy of targeted on-site delivery of encapsulated MSC-IFNβ. Results: We show that tumor debulking results in substantial reduction of myeloid-derived suppressor cells (MDSC) and simultaneous recruitment of CD4/CD8 T cells. This immune response significantly enhanced the antitumor efficacy of locally delivered encapsulated MSC-IFNβ via enhanced selective postsurgical infiltration of CD8 T cells and directly induced cell-cycle arrest in tumor cells, resulting in increased survival of mice. Utilizing encapsulated human MSC-IFNβ in resected orthotopic tumor xenografts of patient-derived GBM, we further show that IFNβ induces cell-cycle arrest followed by apoptosis, resulting in increased survival in immunocompromised mice despite their absence of an intact immune system. Conclusions: This study demonstrates the importance of syngeneic tumor resection models in developing cancer immunotherapies and emphasizes the translational potential of local delivery of immunotherapeutic agents in treating cancer. Clin Cancer Res; 23(22); 7047–58. ©2017 AACR.
SAT0306 Association between quality of sleep, quality of life and disease activity in patients with systemic lupus erythematosus
Authors: S Monov, D Monova, M Ivanova
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic Lupus Erythematosus (SLE) patients are known to have sleep disturbances. Quality of sleep may affect quality of life, but this association has not been systematically evaluated. <h3>Objectives</h3> The aim of this study was to examine the association of quality of sleep, quality of life and SLE disease activity in patients diagnosed with SLE. <h3>Methods</h3> 132 SLE patients with a confirmed diagnosis of SLE according to the ACR classification criteria were enrolled in this study. The patients completed the following questionnaires: the Pittsburgh Sleep Quality Index (PSQI), the 12 item Short Form Health Survey (SF-12), the Lupus Patient-Reported Outcome tool (LupusPRO), SLE Quality of Life Questionnaire (SLE - QoL). Clinical information, including the SLE Disease Activity Index (SLEDAI), was obtained from medical records. Student9s t-test, ANOVA, Pearson correlation measured were used in statistical analysis. <h3>Results</h3> The majority of the participants (84,4%) had sleep disturbances (PSQI &gt;5). Total PSQI score was weakly associated with all of the SF-12 subcategories and showed weak to moderate associations with the LupusPRO subcategories (r &lt;0,05), except for "medication" (r &lt;0,20). "Sleep duration" was not associated with any of the SF-12 or LupusPRO subcategories. "Sleep efficiency" was weakly associated with "physical health", "physical function", and "pain" in the SF-12 and LupusPRO. "Sleep quality" and "sleep disturbances" were weakly associated with "pain" and the "emotional" and "mental" subcategories in the SF-12 and LupusPRO. SLE - QoL was significantly higher in patients with good sleep. <h3>Conclusions</h3> We found that quality of sleep, especially "sleep efficiency", was poor for the majority of patients with SLE. Quality of sleep was associated with various aspects of quality of life, especially pain, vitality, and emotional health. Management of pain and emotional health may be important for improving quality of sleep in SLE patients. <h3>Disclosure of Interest</h3> None declared
Stereotactic interstitial radiosurgery using the Photon Radiosurgery System in the minimally-invasive treatment of selected tumors in the thalamus and the basal ganglia
Authors: P. Gallina, P. Francescon, C. Cavedon, F. Casamassima, R. Mungai, P. Perrini, S. Poggi, A.M. Buccoliero, M. Pulidori, H. Mouchaty, N. Di Lorenzo
Journal: Neuro-Oncology (2002)
THU0189 Safety of four treatment regimens in early rheumatoid arthritis
Authors: E Fedorenko, G Lukina, Y Sigidin, D Karateev
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To compare safety data in patients (pts) with early (&lt;2 years duration) RA who were randomised to receive 4 different regimens of treatment. <h3>Methods</h3> One hundred forty-one pts with RA of less than 2 years duration (122 women, mean age 51 years, mean disease duration 24 weeks, mean DAS 28 5,9; 64% RF-positive,59% ACCP-positive) were randomly allocated to receive one of the following treatment regimens: methotrexate (MTX, up to 20 mg/week, 35 pts); MTX plus prednisolone (P) 10 mg daily (MTX-P, 34 pts); MTX-P plus methylprednisolone (MP) 1000 mg intravenously on the first day of treatment (MTX-P-MP, 35 pts); leflunomide 20 mg daily (LEF, 37 pts). Duration of treatment was one year. Control points were 3, 6 and 12 months from the initiation of therapy. Safety data was assessed at the main control points. <h3>Results</h3> One hundred twenty-seven pts completed the study. Side effects were registered in the same number of patients in each group (9 patients; 24,3%&gt;26%). Therapy had to be stopped in six patients due to side effects: MTX - 1 (depigmentation of the skin), MTX-P - none, MTX-P-MP - 1 (stomatitis) and LEF - 4 (dermatitis-2; pancytopenia with platelet count 43 ×10<sup>9</sup>/L, erythrocyte 2,9×10<sup>12</sup>/L, WBC 2×10<sup>9</sup>/L-1; angioedema, periorbital edema and dermatitis with itching-1). Other side effects were mild: MTX - 8 pts (dyspepsia-1, elevation of transaminases-6, hair loss-1), MTX-P - 9 pts (Cushing9s syndrome - 1, hair loss - 1, anemia - 1, elevation of transaminases - 4, arterial hypertension - 2), MTX-P-MP - 8 pts (hair loss-1,dermatitis-1, elevation of transaminases-5, Cushing9s syndrome - 1) and LEF - 5 pts (elevation of transaminases-5). At baseline all groups were comparable in their demographic, clinical and radiographic characteristics. <h3>Conclusions</h3> In most cases side effects were moderate or minimal. The most serious side effects, leading to the discontinuation of the therapy, were registered in LEF group. There was no withdrawal of treatment in MTX-P group. Safety profile was the same in all groups. <h3>Disclosure of Interest</h3> None declared
新しいlipoproteoplexは糖尿病性創傷治癒を促進するためのKeap1siRNAベース遺伝子治療を提供する【Powered by NICT】
Authors: S Rabbani Piul, Zhou Anna, M Borab Zachary, A Frezzo Joseph, Srivastava Nikita, T More Haresh, J Rifkin William, A David Joshua, J Berens Samuel, Chen Raymond, Hameedi Sophia, H Junejo Muhammad, Kim Camille, A Sartor Rita, F Liu Che, B Saadeh Pierre, K Montclare Jin, J Ceradini Daniel
Journal: Biomaterials (2017)
OP0092 Interleukin 37 reverses the metabolic cost of inflammation, increases oxidative respiration and improves exercise tolerance
Authors: G Cavalli, D Ballak, JJ Justice, K Boyle, A D'Alessandro, LA Joosten, L Dagna, CA Dinarello
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The IL-1 family cytokine interleukin 37 (IL-37) has broad anti-inflammatory effects and functions as a natural suppressor of innate inflammation and acquired immunity (1). We have reported that administration of recombinant human IL-37 to wild type mice or expression in mice transgenic for human IL-37 suppress proinflammatory cytokines and curb excessive inflammation in various conditions including inflammatory arthritis (2). Besides these anti-inflammatory effects, IL-37 also induces complex effects on metabolism. In particular, IL-37 can directly activate AMP-activated protein kinase (AMPK), a central regulator of cellular energy homeostasis and exercise-regulated metabolism (3). <h3>Objectives</h3> In this study, we evaluate the effects of IL-37 treatment on exercise tolerance in mice with systemic inflammation induced by LPS injection. We further investigate the effects of IL-37 on exercise tolerance in healthy mice, with specific focus on the metabolic changes induced by IL-37 administration and possibly responsible for a reduction in the metabolic costs of inflammation. <h3>Results</h3> Exogenous administration of IL-37 to healthy mice, not subjected to an inflammatory challenge, also improved exercise performance by 82% compared to vehicle-treated mice (<i>p</i>=0.01). Treatment with 8 daily doses of IL-37 resulted in a further 326% increase in endurance running time compared to the performance level of mice receiving vehicle (<i>p</i>=0.001). These properties required the engagement of the IL-1 decoy receptor 8 (IL-1R8) and the activation of AMP-activated protein kinase (AMPK), since both inhibition of AMPK and IL-1R8 deficiency abrogated the positive effects of IL-37 on exercise performance. Mechanistically, treatment with IL-37 induced marked metabolic changes with higher levels of muscle AMPK, greater rates of oxygen consumption and increased oxidative phosphorylation. Metabolomic analyses of plasma and muscles of mice treated with IL-37 revealed an increase in AMP/ATP ratio, reduced levels of pro-inflammatory mediator succinate and oxidative stress-related metabolites as well as changes in amino acid and purine metabolism. <h3>Conclusions</h3> These effects of IL-37 to limit the metabolic costs of chronic inflammation and to foster exercise tolerance provide a rationale for therapeutic use of IL-37 in the treatment of inflammation-mediated fatigue. <h3>References</h3> Dinarello CA, et al. (2016) Suppression of innate inflammation and immunity by interleukin-37. Eur J Immunol. Cavalli G, et al. (2016) Treating experimental arthritis with the innate immune inhibitor interleukin-37 reduces joint and systemic inflammation. Rheumatology (Oxford). Ballak DB, et al. (2014) IL-37 protects against obesity-induced inflammation and insulin resistance. Nature communications. <h3>Disclosure of Interest</h3> None declared
Alveolar eosinophilia in current smokers with chronic obstructive pulmonary disease in the SPIROMICS cohort
Authors: Carlos H. Martinez, Sara X. Li, Andrew J. Hirzel, Valerie R. Stolberg, Neil E. Alexis, R. Graham Barr, Eugene R. Bleecker, Elizabeth E. Carretta, Stephanie A. Christenson, Christopher B. Cooper, David J. Couper, Claire M. Doerschuk, MeiLan K. Han, Nadia N. Hansel, Annette T. Hastie, Eric A. Hoffman, Robert J. Kaner, Fernando J. Martinez, Deborah A. Meyers, Wanda K. O'Neal, Robert Paine, Nirupama Putcha, Stephen I. Rennard, Prescott G. Woodruff, Michelle Zeidler, Jeffrey L. Curtis, Christine M. Freeman
Journal: Journal of Allergy and Clinical Immunology (2017)