tbuckley/cabot-search huggingface dataset:
CTLA4 and CD47 combinational therapy to extend survival in melanoma.
Authors: Anthony L. Schwartz, Pulak Nath, Elizabeth Lessey-Morillon, Lisa Ridnour, Michael Allgaeuer, David Roberts
Journal: Journal of Clinical Oncology (2017)

e21025 Background: Irradiation (IR) combined with chemotherapy is the post-surgical standard of care treatment for melanoma, but metastasis still results in high mortality rates. Immune checkpoint inhibitors such as cytotoxic T-lymphocyte antigen-4 (CTLA4) have proven effective for immunotherapy of melanoma. CTLA-4 is up-regulated post-T cell activation and blockade enhances tumor responses in immunocompetent rodents and humans. Trials suggest that combinations of immune checkpoint inhibitors are more efficacious than single agents, but tumors remain resistant. We are investigating CD47 blockade for the treatment of cancer. CD47 is frequently elevated in cancers and serves as an inhibitory receptor for thrombospondin-1 on immune cells in the tumor stroma. CD47 blockade on CD8 T or tumor cells significantly enhances immune-targeted tumor cell killing post-IR compared to IR alone. Here we explore the potential for antisense CD47 and anti-CTLA4 therapy alone or in combination with IR using a syngeneic mouse melanoma model. Methods: C57BL/6 mice were inoculated with 1x10 6 B16F10 melanoma cells in the hind limb and treated with 10 Gy IR combined with CTLA4 blocking antibody, CD47 translational blocking morpholino, or the combination of CTLA4/CD47 therapies. Granzyme B along with CD4/CD8 T cell infiltration were examined in tumors. Histology was evaluated for CD3 and necrosis. Results: The combination of CD47/CTLA4 with IR significantly increased survival by 25% compared to IR/CTLA4 alone at 50 days. Granzyme B expression was significantly increased in IR mice with CTLA4/CD47 combination, which correlated with infiltration of CD8+ T cells and a concomitant decrease in Gr1+CD11b suppressor cells compared to controls. In non-IR tumors, histology revealed minimal necrosis, while all IR groups showed increased necrosis. Tumor IR in combination with CTLA4 or CD47 increased immune cell infiltration. However, the combination of IR with CTLA4/CD47 showed widespread necrosis. All groups treated with the CD47 exhibited focal hemorrhage, which was more extensive when combined with CTLA4. Conclusions: Results herein suggest IR combined CTLA4/CD47 checkpoint blockade provides a survival benefit by activating a beneficial adaptive immune response.
SP0026 Novel imaging techniques for assessing osteoporotic fracture risk
Authors: R Chapurlat
Journal: Annals of the Rheumatic Diseases (2017)

The measurement of areal bone mineral density (aBMD) by dual x-ray absorptiometry (DXA) has been the mainstay for the diagnosis of osteoporosis for at least two decades. The sensitivity and specificity of this test, however, remains suboptimal. For example, more than 50% of postmenopausal women with fragility fracture are not identified with DXA. A great deal of research has been performed recently to develop alternative or complementary imaging techniques to overcome DXA predictive limitations. These techniques are based on the non invasive analysis of bone microarchitecture and estimation of bone strength by finite element analysis (FEA). Texture analysis uses mathematical models based on fractal analysis to evaluate bone microarchitecture using various types of bone images. The trabecular bone score (TBS) has emerged as an approach that may improve fracture risk prediction. The TBS is based on the texture analysis of the DXA lumbar spine image to quantify bone microarchitecture. Several cohort studies have shown that a subset of individuals could be reclassified with TBS. A meta-analysis results have allowed for incorporation of the TBS in the FRAX score calculation, that is widely available. The measurement of volumetric BMD with quantitative computerized tomography (QCT) at the hip has been shown to predict fracture risk. These images can also be used to perform FEA that may increase the fracture risk prediction. The additional value of this technique compared with DXA remains to be established in a clinical setting. Bone microarchitecture can also be assessed at peripheral sites such as the distal radius and tibia using high resolution peripheral quantitative tomography (HRpQCT). Numerous cross-sectional and case-control studies have shown a significant association between prevalent fracture and bone microarchitecture and estimated bone strength assessed with FEA. The bone parameters measured at distal sites are also associated with fractures at distant sites, e.g., the vertebrae and the femoral neck. In a recent prospective study, bone microarchitecture at the distal radius - especially the trabecular vBMD - has been associated with incident osteoporotic fracture. The FEA models were also predictive of fragility fracture. The best models and the most appropriate architectural parameters - whether they are trabecular of cortical - remain to be dissected out and their comparative diagnostic value with aBMD by DXA remains to be established. The measurement of the TBS may allow for reclassification of a subset of postmenopausal women at higher risk for fracture whereas they display a moderately reduced aBMD. Hip QCT and HRpQCT may also improve the prediction for fracture, but they are still research techniques. <h3>Disclosure of Interest</h3> None declared
SP0140 Patient engagement in research: a pcori exemplar
Authors: J Poole
Journal: Annals of the Rheumatic Diseases (2017)

This session will discuss patient and stakeholder involvement as members of the research team on a grant funded by the Patient Centered Outcomes Research Institute (PCORI). Patients with a rare chronic disease, systemic sclerosis, and members from key stakeholder organizations were involved in evaluating, revising and testing the effectiveness of an internet self-management program. They participated at several levels of engagement including planning the study, conducting the study, and disseminating the results. This session will discuss how engagement occurred at each of these levels through different opportunities such as creating interventions, identifying outcomes, recruiting, presenting findings, and planning dissemination efforts. The benefits and challenges for both researchers and patient research partners will also be described. <h3>Disclosure of Interest</h3> None declared
4 hs-cTnI algorithms had high sensitivity and low failure rates for ruling out acute MI in the ED
Authors: Andrew Worster, Peter Kavsak
Journal: Annals of Internal Medicine (2017)

Source Citation Boeddinghaus J, Nestelberger T, Twerenbold R, et al. Direct comparison of 4 very early rule-out strategies for acute myocardial infarction using high-sensitivity cardiac troponin I. Circulation. 2017;135:1597-611. 28283497
Afatinib (Afa) plus bevacizumab (Bev) combination after acquired resistance (AR) to EGFR-tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC): Multicenter single arm phase II trial (ABC-study).
Authors: Akito Hata, Nobuyuki Katakami, Reiko Kaji, Toshihide Yokoyama, Toshihiko Kaneda, Motohiro Tamiya, Takako Inoue, Hiromi Kimura, Yukihiro Yano, Daisuke Tamura, Satoshi Morita, Shunichi Negoro
Journal: Journal of Clinical Oncology (2017)

9034 Background: Irreversible EGFR-TKI monotherapies showed only moderate efficacy after AR to reversible EGFR-TKIs. Preclinical studies suggested that addition of Bev to EGFR-TKIs could overcome AR, and Bev demonstrated synergistic effects with Afa in TKI-resistant xenograft models. Methods: ECOG PS 0-2 patients (pts) with EGFR-mutant NSCLC after AR to EGFR-TKIs were enrolled at any lines. Rebiopsy was essential to confirm T790M status after AR. Afa was prescribed at 30 mg, and Bev administered at 15 mg/kg tri-weekly until progression. Results: Between October 2014 and September 2016, 33 eligible pts were enrolled. Median age was 66 (range, 48-86). Twenty-one (64%) pts were female, and 22 (67%) were never smoker. Mutation subtypes were 20 (61%) Del-19, 12 (36%) L858R, and 1 (3%) L861Q. T790M was detected in 14 (42%) pts. Median number of prior regimens was 4 (range, 1-10). First prior TKIs were 20 (61%) gefitinib, 10 (30%) erlotinib or 3 (9%) Afa. Six pts obtained partial response and 23 stable disease, resulting in response rate (RR) of 18.2% (95% confidence interval [CI], 7.0-35.5%) and disease control rated of 87.9% (95% CI, 71.8-96.6%). Median progression-free survival (PFS) and overall survival were 5.9 (95% CI, 3.5-8.8) months and not reached, respectively. Median RR and PFS of T790M+ vs. T790M- were 14.3% vs. 21.2% (p = 0.6189) and 6.2 vs. 5.2 months (p = 0.8619), respectively. Median RR and PFS of Del-19 vs. L858R were 20.0% vs. 8.3% (p = 0.3789) and 5.9 vs. 5.1 months (p = 0.8996), respectively. Afa dosage was reduced to 20 mg in 15 (45%) pts and increased to 40 mg in 2 (6%) pts. Median number of Bev administrations was 6 (range, 1-14). Bev was interrupted in 5 (15%) pts. Adverse events ≥grade 3: rash (3%); paronychia (24%); mucositis (6%); diarrhea (3%); liver dysfunction (3%); hypertension (39%); and proteinuria (15%) were observed. There were no treatment-related deaths, interstitial lung disease, nor Bev-associated severe bleedings. Conclusions: Afa + Bev demonstrated the efficacy and safety after AR to EGFR-TKIs. It could be a therapeutic salvage option for T790M- populations. Clinical trial information: UMIN000014710.
THU0309 Treatment with methotrexate and risk of relapses in patients with giant cell arteritis in clinical practice
Authors: D Núñez Freites, J Font, C Leόn, I Morado, L Rodríguez-Rodríguez, L Leόn, Z Rosales, B Fernández, J Jover, L Abásolo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To assess the incidence rate of relapses and to analyze the risk of relapses in patients with <i>Giant Cell Arteritis</i> (GCA) treated with and without <i>Methotrexate</i> (MTX), in clinical practice. Other factors associated were also investigated. <h3>Methods</h3> An inception cohort of GCA was assembled in the out-patient clinic at Hospital Clinico San Carlos, including patients from the date of diagnosis (Jan-1991 until Sept-2013), and followed-up until Sept-2014. Main outcome: relapses defined as after an objective improvement, patient has again symptoms or signs of GCA with high ESR and the need to increase corticosteroids at least 10mg. The independent variable was exposure to MTX over time. Covariables: Sociodemographic, clinical, and treatment. Incidence rates of relapses (IR) per 100 patient-years with their 95% confidence intervals [CI] were estimated using survival techniques. Time of exposure comprised the period from diagnosis until: lost of follow-up, main outcome, exposure to MTX or the end of the study. MTX influence on IR was analyzed by multivariable Cox models. <h3>Results</h3> 168 patients were included (675 patient-years). 80% of them were female, with a mean age of 76±7 years. 65% of the patients were on MTX, with mean dose of 10 mg/week. 31% of patients had relapses with an IR of 12 [9.6–14.9]. The median number of relapses was 1 [1–2], with a median lag time of 1.6 [0.6–6.3] years. In the multivariate analysis, exposure to MTX had less risk of flaring compared to those never on MTX (p&lt;0.05). Other variables included in the final model were: visual alterations, constitutional symptoms or malaise at clinical presentation of GCA. <h3>Conclusions</h3> The use of MTX seems to decrease the risk of recurrences. We also found other factors influencing on flares. <h3>Disclosure of Interest</h3> None declared
AB0401 The efficent regulation of tocilizumab for the expression of CD4+/CD8+ T/CD19 + B cells and the immunoglobulin in systemic juvenile idiopathic arthritis
Authors: H Li, H Zeng
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To study the influence of tocilizumab on lymphocyte subsets, immunoglobulin and biochemical indicators of Systemic juvenile idiopathic arthritis. <h3>Methods</h3> DMARDs poor efficacy in children with severe SJIA 18 patients were divided into two groups, of which eight patients tocilizumab + DMARDs group (in cluding a case of refractory MAS), 10 patients in the placebo + DMARDs control group, according to the weight&gt;30kg, 8mg/kg, &lt;30kg, 12mg/kg, injected once every two weeks in hospital.Symptoms and CD3 +, CD4 +, CD8 + T, CD19 + B, CD16 + 56-NK cell ratio in two groups were observed by the flow cytometry before or after 12 weeks treatment. Comparing immunoglobulin IgG, IgM, IgA, IgE with baseline after the therepy in two group, and continuous observe inflammatory markers (CRP, ESR, FER, WBC) and ALT/AST changes, adverse reactions and reduce stopping hormone case inductive analysis in following 12 weeks. <h3>Results</h3> After 12 weeks, tocilizumab + DMARDs group, CRP, ESR, FER were significantly decreased, the most frequently occurring adverse reaction was infection, mostly upper respiratory tract infection, followed by elevated transaminase, cholesterol, low-density lipoprotein High-density lipoprotein and triglyceride levels increased; two groups no serious adverse events (three-line reduction, severe infections, etc.). the proportion of CD4 + T, CD19 + B cells in Tocilizumab group were lower than baseline (P&lt;0.05), CD8, CD3 + T cells were increased in comparing with baseline, however,no significant change with CD16 + 56-NK cells (P&gt;0.05), and immunoglobulins IgG, IgM, IgA lower than baseline (P&lt;0.05). The control group had no significant difference (P&gt;0.05). <h3>Conclusions</h3> Tocilizumab can significantly reduce inflammatory markers (CRP, ESR, FER), but affect lipid metabolism and ALT/AST.Blocking IL-6 can be adjusted hyperthyroidism humoral and regulate CD4 + T, CD19 + B cells, reduce joint destruction. Tocilizumab can effectively control the development of DMARDs poor efficacy SJIA. <h3>Disclosure of Interest</h3> None declared
Patent Foramen Ovale after Cryptogenic Stroke — Assessing the Evidence for Closure
Authors: Andrew Farb, Nicole G. Ibrahim, Bram D. Zuckerman
Journal: New England Journal of Medicine (2017)

The benefit of closing a patent foramen ovale after a cryptogenic stroke has been an open question. The FDA recently approved the Amplatzer PFO Occluder in light of a nonsignificant reduction in recurrent ischemic stroke with the device and a favorable safety profile.
AB0347 Evaluation of the impact of rheumatoid arthritis on sexual function
Authors: M Brahem, H Hachfi, S Ben Hammouda, I Haddada, M Maraoui, M Jguirim, M Younes
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) may affect all aspects of life including sexual functioning.The percentage of arthritic patients who experience sexual problems ranged in various studies from 31% to 76%.The reasons for disturbing sexual functioning are multi-factorial and comprise disease-related factors as well as therapy.It can occur before, during and after sexual activities, and can affect sexual health in different perspectives. <h3>Objectives</h3> The aim of our study is to evaluate the impact of the RA in sexual function and its associated factors. <h3>Methods</h3> This is a cross-sectional and descriptive study during a period of the year 2016, including 37 patients followed in the department of Rheumatology in Mahdia Tunisia. All patients were diagnosed with RA based in ACR 1987/EULAR 2010. We evaluated for each patient the sexual quotient (QS). It is a validated scale which estimates the degree of satisfaction of the sex life. <h3>Results</h3> The age of the RA patients (32 females/5 males) ranged from 21 to 76 years. The mean age was 53.1±12 years. The mean duration of the disease was 11±10 years [1–34]. The mean number of tender joints was 13.2±9.6 and swollen joint was 5.9±7. The mean DAS28 was 5.5±1.5 [2.9–8.2] and HAQ was 1.6±0.9 [0–2.8]. 51.3% of patients had specific joint deformations, 83.8% had radiologic involvement and 29.7% had osteoporosis. The biologic analysis showed that the mean ESR was 45±27.1 and the CRP was 13.7±25.3. Rheumatoid factors were positive in 37.8% of cases, the ACPA were positive in 32.4% of cases. 81.1% of RA patients were treated by methotrexate and 13.5% were treated by biologic treatments. The mean sexual quotient was 50.25±20.8 [6–87.5]; only 8.1% of patients had a great sexual life (QS between 80 and 100), 16.2% expressed some sexual satisfaction (QS between 60 and 80), 21.6% had a mild sexual life (QS between 40 and 60), 18.9% presented a disappointing sexual life (QS between 20 and 40) and 35.4% didn9t have any partner. Our study showed a significant correlation between the duration of the disease and the alteration of the sexual quotient, but no correlation with the clinical and biological parameters of RA. <h3>Conclusions</h3> We conclude that only 24.3% of our RA patients had satisfaction in their sexual life. This alteration of the sexual quotient was found to be correlated with the duration of the disease. This fact may be explicated by the disability, fatigue and pain caused by this chronic inflammatory disease. This relation should be confirmed by future studies. <h3>References</h3> Antonio G Tristano, Impact of rheumatoid arthritis on sexual function, World J Orthop 2014 April 18; 5(2): 107–111. Abdo J. Sex Med. 2007;4:382–389. Kraaimaat FW, et al, Intrusiveness of rheumatoid arthritis on sexuality in male and female patients living with a spouse. Arthritis Care Res 1996; 9:120–125. <h3>Disclosure of Interest</h3> None declared
AB0994 Anti TNF-ALPHA therapy would be lifesaving in deficiency of adenosine deaminase-2
Authors: S Sahin, A Adrovic, K Barut, S Ugurlu, ET Turanli, H Ozdogan, O Kasapcopur
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Deficiency of adenosine deaminase-2 (DADA2) is a rare form of autoinflammatory disorder with limited reported cases. <h3>Objectives</h3> In this study, we have characterized the clinico-immunological, radiological and genetic characteristics of eight childhood-onset DADA2 patients. We aimed to compare these features between surviving and deceased patients. <h3>Methods</h3> Demographic features, clinical characteristics, imaging findings, mutations and pharmacological treatments compared between surviving and deceased DADA2 patients. <h3>Results</h3> Eight patients from seven families were enrolled. While five of them were still surviving, three of them had died due to various reasons. Median age of the patients at disease onset and diagnosis were 7 years (range 0.5–13 years) and 14 years (range 5–27years), respectively. The main clinical manifestations were cutaneous manifestations (7/8), recurrent low-grade fever (6/8), neurological involvement (6/8) and gastrointestinal involvement (5/8). All patients had increased acute phase reactants at presentation and also during flares. Until the diagnosis of DADA2, five patients have been followed-up with the diagnosis of PAN; two patients both with PAN and FMF, and one patient with CAPS and vasculitis. Demographic, clinical, neurological features and genetic mutations did not differ in surviving and deceased DADA2 patients. Deceased and surviving subjects differed in terms of medication usage after the diagnosis of DADA2. Anti-TNF alpha treatment has been initiated in 5 surviving patients soon after the diagnosis of DADA2. However, unfortunately three patients who have died, were able to use either a few doses of anti-TNF alpha treatment or none; one patient due to reluctance of patient and two patients due to establishment of a definite diagnosis with genetic analysis after the patients had died. <h3>Conclusions</h3> Although this study includes limited number of patient, to our knowledge this study for the first time compares the phenotypic, genotypic and medication differences between surviving and deceased DADA2 patients. Anti-TNF alpha treatment seems to be very efficient and lifesaving in DADA2 patients. <h3>References</h3> Zhou Q, Yang D, Ombrello AK, et al. Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med 2014;370(10):911–20. Navon Elkan P, Pierce SB, Segel R, et al. Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. N Engl J Med 2014;370(10):921–31. Garg N, Kasapcopur O, Foster J, et al. Novel adenosine deaminase 2 mutations in a child with a fatal vasculopathy. Eur J Pediatr 2014;173:827–30. <h3>Disclosure of Interest</h3> None declared
SAT0357 Features associated with moderate to high risk of malnutrition in a cohort of patients with systemic sclerosis
Authors: PM Marcaida, D Vanesa, V Martire, F Melo, A Secco, M Mamani, S Scarafia, M Lazaro, A Cusa, F Cusa, V Caputo, J Sarano, M Molina, A Nitsche, M Gaona, C Pena, M Garcia, S Gordon, N Muñoz Cantos, S Montoya
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> It is estimated that about 28% of Systemic Sclerosis (SS) patients have moderate to high risk of malnutrition. <h3>Objectives</h3> to evaluate differences between SS patients with moderate to high risk of malnutrition and those with low risk. <h3>Methods</h3> cross-sectional, observational, multicentric study. We included patients with SS according to ACR-EULAR 2013 classification criteria. Patients were classified in groups depending on whether they were in low or moderate-high risk of malnutrition, according to the screening method for detection of adult malnutrition (MUST). Were evaluated: disease duration, disease subtype (limited or diffuse), presence of microstomia, xerostomia, active or past digital ulcers, amputations, arthritis, Rodnan Score, gastroesophageal and bowel involvement, anxiety and depression, and hands functionality by Duruöz Index. Continuous variables were described as median (IQR) or mean (SD) and percentages for categorical variables. Mann Whitney or t-test was used for continuous variables, and Fisher exact test or chi squared for categorical variables. A <i>p</i>&lt;0.05 was considered significant. A multivariate analysis was made taking MUST as a dependent variable. <h3>Results</h3> 116 patients were included. Thirty percent were at moderate to high risk of malnutrition. These patients experienced significantly higher frequency of diffuse SS (49% vs 21%, <i>p</i>=0,003), bowel involvement (49% vs 27%. <i>p</i>=0,02), gastroesophageal involvement (74% vs 48%, <i>p</i>=0,009), higher cutaneous involvement (<i>median</i> 12 vs 6, <i>p</i>=&lt;0,01), microstomia (40% vs 15%, <i>p</i>=0,003), worst hand functionality (<i>median:</i> 11 vs 3, <i>p</i>=0,02), and moderate-severe depression (37% vs 16%, <i>p</i>=0,012). Also, men experienced a higher moderate-high risk of malnutrition (20% vs 6%, <i>p</i>=0,02). In the multivariate analysis, the male sex (OR 4.55, 95% CI 1.11–20, p=0.03), the Rodnan score &gt;9 (OR 3.13, 95% CI, 95% CI, p=0,01), and gastroesophageal involvement (OR 2.87, 95% CI 1.07–7.73, p=0.03), were independently and statistically significant. <h3>Conclusions</h3> These results highlight the importance of assessing the nutritional status of our SS patients. <h3>Disclosure of Interest</h3> None declared