tbuckley/cabot-search huggingface dataset:
Abstract 12851: Osteoprotegerin is Associated With Major Bleeding but Not With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes - Insights From the PLATelet Inhibition and Patient Outcomes (PLATO) Trial
Authors: Thor Ueland, Axel Åkerblom, Tatevik Ghukasyan, Annika E Michelsen, Pål Aukrust, Richard C Becker, Maria Bertilsson, Anders Himmelmann, Stefan K James, Agneta Siegbahn, Robert F Storey, Frederic Kontny, Lars Wallentin
Journal: Circulation (2016)

Introduction: Elevated plasma levels of osteoprotegerin (OPG), a secreted cytokine receptor, might be associated with increased cardiovascular (CV) risk. Methods: We measured plasma OPG levels obtained on admission and at 1 month in a pre-defined subset of patients with acute coronary syndromes (ACS) randomized to 6 - 12 months treatment with ticagrelor or clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) trial (NCT00391872) . OPG was determined by enzyme immuno-assay. Rates of CV outcomes and major bleeding were presented by baseline OPG quartile groups. The multivariable associations of OPG levels (log transformed) with the composite endpoint of CV death, non-procedural spontaneous myocardial infarction (sMI) or stroke, and with non-CABG major bleeding were assessed with Cox proportional hazards models. Five adjusted models, with co-variates and incremental addition of log transformed biomarkers, were used: 1/ randomized treatment and clinical risk factors (including: age, gender and, hypertension e.g.) 2/ CRP and white blood cell count (WBC), 3/ cystatin C, 4/ hs-Troponin T and NT-proBNP and 5/ growth differentiation factor (GDF)-15. Results: OPG levels were available in 5,135 (28%) patients at baseline, with a median (interquartile interval) of 2.7 (2.0 - 3.6) ng/mL. Event rates of the composite endpoint per increasing quartile group were; 5.2%, 7.5%, 9.2% and 11.9%; and for non-CABG major bleeding: 2.4%, 2.2%, 3.8% and 7.2%. OPG levels at 1 month (n= 3,668), in patients free from any outcome event, were likewise independently associated with bleeding during follow up (n=69); with an adjusted HR of 1.43 (1.04-1.96). There was no interaction between admission OPG levels and randomized treatment. Conclusion: In multivariable analysis, osteoprotegerin was a strong and independent marker of major bleeding but not of ischemic CV events. Thus, OPG seems to provide important independent information on bleeding risk in patients with ACS.
AB0265 The significance of early diagnosis and prognostic evaluation of four kinds of ANTI-CCP antibodies in various types of juvenile idiopathic arthritis
Authors: P Zeng, H Zeng
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To investigate the relationship between immunological parameters AKA, anti - CCP, the RF- IGG, RF-IGM and the early diagnosis and prognosis in sub- JIA patients. <h3>Methods</h3> Collection of 76 JIA patients in our hospital with system treatment and adhere to the follow-up treatment for at least six months, detect the immunological parameters of AKA, anti- CCP, RF-IGG, RF-IGM in the early diagnosis, compare the Positive rate in different subtypes and prognosis, and make the statistical analysis of sensitivity, specificity and relevant risk, compare to the normal control group of blood of 49 healthy children. <h3>Results</h3> There is a significant difference between polyarticular group and normal control group in positive rate of AKA, anti-CCP, RF-IGG, RF-IGM, there is no significant difference between the type of systemic, oligoarticular, enthesitis and the normal control group in autoantibody-positive detection rate. Polyarticular group9s sensitivity AKA &gt; anti-CCP, RF-IGG &gt; RF-IGM and four kinds of joint detection, specificity RF-IGM, four kinds of joint detection &gt; AKA &gt; RFIGG &gt; anti-CCP. There is a significantly different between refractory JIA and general JIA patients in AKA positive rate, relative risk OR is 3.514%. <h3>Conclusions</h3> The effect of AKA, anti-CCP, RF- IGG, RF-IGM in the different subtypes of JIA about early diagnosis are different, it is found that AKA, anti-CCP has good sensitivity and specificity in polyarticular JIA, AKA appears relate with refractory JIA, it is a large sample of the study to be confirmed that whether it can be a serological marker in the early diagnosis and prognosis of Polyarticular JIA. <h3>Disclosure of Interest</h3> None declared
An economic analysis of arthralgia/myalgia (A/M) versus recurrence in women with hormone receptor-positive (HR+) breast cancer (BC) on aromatase inhibitors (AIs)
Authors: P. Hadji
Journal: Journal of Clinical Oncology (2009)

e11601 Background: The symptoms of A/M are associated with estrogen suppression and are more common with AIs relative to tamoxifen (TAM). AIs have demonstrated superior efficacy when compared with TAM. In BIG 1–98, letrozole (LET) treatment provides a significant reduction in the risk of distant metastasis (DM); the updated 76 month BIG 1–98 analysis now suggests that early reduction in DM ultimately leads to overall survival (OS) benefit, 40 fewer deaths with LET compared with TAM. [Mouridsen, 2008] It has been reported that women reporting new joint symptoms at 3 months after initiating an AI have a significantly lower risk for recurrence compared with women not reporting these symptoms [Cuzick, 2008]. Methods: Data from the Henry Ford Health System (1995–2005) were used to identify postmenopausal HR+ early BC patients with at least 1 year of AI therapy follow-up after surgery. Total health care costs of managing A/M associated with hormone therapy as well as BC recurrences were estimated from charges incurred during health care encounters for these conditions. Results: In the 834 patients eligible, the treated A/M incidence was 21% and the total health care cost ∼ $429 per symptomatic patient/yr. The average annual cost of any BC recurrence was previously reported at ∼$131,000/yr, with greatest cost seen with DM at ∼ $265,783/yr [Weiderkehr, 2008]. Conclusions: The economic costs of treating A/M are nominal, particularly in light of the superior efficacy of AIs and the economic burden of BC recurrences. DM is the most costly of the recurrences, and in BIG 1–98, reducing early DM appears to impact OS. Discontinuation of AIs, or switching to less effective therapies in an effort to manage A/M, should be weighed against the benefit of AI therapy in reducing BC recurrences, particularly DM, as well as the high costs associated the managing these recurrences. No significant financial relationships to disclose.
Overexpression of miR-194 Reverses HMGA2-driven Signatures in Colorectal Cancer
Authors: Hsin-Yi Chang, Shu-Ping Ye, Shiow-Lin Pan, Tzu-Ting Kuo, Bia Chia Liu, Yi-Lin Chen, Tsui-Chin Huang
Journal: Theranostics (2017)

Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide with increasing incidence and mortality in developed countries.Oncogenes and microRNAs regulate key signaling pathways in CRC and are known to be deregulated.Oncogenic transcriptional regulator high-mobility group AT-hook 2 (HMGA2) participates in the transformation of several cancers including CRC and exhibits strong correlation with poor prognosis and distal metastasis.Evidence of HMGA2 and its co-regulated miRs contributing to tumor progression remains to be clarified.Methods: We performed gene-set enrichment analysis on the expression profiles of 70 CRC patients and revealed HMGA2 correlated genes that are targeted by several miRs including miR-194.To eliminate the oncogenic effects in HMGA2-driven CRC, we re-expressed miR-194 and found that miR-194 functions as a tumor suppressor by reducing cell proliferation and tumor growth in vitro and in vivo.Results: As a direct upstream inhibitory regulator of miR-194, overexpression of HMGA2 reduced miR-194 expression and biological activity, whereas re-expressing miR-194 in cells with high levels of HMGA2 impaired the effects of HMGA2, compromising cell survival, the epithelial-mesenchymal transition process, and drug resistance.Conclusion: Our findings demonstrate that novel molecular correlations can be discovered by revisiting transcriptome profiles.We uncover that miR-194 is as important as HMGA2, and both coordinately regulate the oncogenesis of CRC with inverted behaviors, revealing alternative molecular therapeutics for CRC patients with high HMGA2 expression.
Glioma Dual-Targeting Nanohybrid Protein Toxin Constructed by Intein-Mediated Site-Specific Ligation for Multistage Booster Delivery
Authors: Yingzhi Chen, Meng Zhang, Hongyue Jin, Dongdong Li, Fan Xu, Aihua Wu, Jinyu Wang, Yongzhuo Huang
Journal: Theranostics (2017)

Malignant glioma is one of the most untreatable cancers because of the formidable blood-brain barrier (BBB), through which few therapeutics can penetrate and reach the tumors. Biologics have been booming in cancer therapy in the past two decades, but their application in brain tumor has long been ignored due to the impermeable nature of BBB against effective delivery of biologics. Indeed, it is a long unsolved problem for brain delivery of macromolecular drugs, which becomes the Holy Grail in medical and pharmaceutical sciences. Even assisting by targeting ligands, protein brain delivery still remains challenging because of the synthesis difficulties of ligand-modified proteins. Herein, we propose a rocket-like, multistage booster delivery system of a protein toxin, trichosanthin (TCS), for antiglioma treatment. TCS is a ribosome-inactivating protein with the potent activity against various solid tumors but lack of specific action and cell penetration ability. To overcome the challenge of its poor druggability and site-specific modification, intein-mediated ligation was applied, by which a gelatinase-cleavable peptide and cell-penetrating peptide (CPP)-fused recombinant TCS toxin can be site-specifically conjugated to lactoferrin (LF), thus constructing a BBB-penetrating, gelatinase-activatable cell-penetrating nanohybrid TCS toxin. This nanohybrid TCS system is featured by the multistage booster strategy for glioma dual-targeting delivery. First, LF can target to the BBB-overexpressing low-density lipoprotein receptor-related protein-1 (LRP-1), and assist with BBB penetration. Second, once reaching the tumor site, the gelatinase-cleavable peptide acts as a separator responsive to the glioma-associated matrix metalloproteinases (MMPs), thus releasing to the CPP-fused toxin. Third, CPP mediates intratumoral and intracellular penetration of TCS toxin, thereby enhancing its antitumor activity. The BBB penetration and MMP-2-activability of this delivery system were demonstrated. The antiglioma activity was evaluated in the subcutaneous and orthotopic animal models. Our work provides a useful protocol for improving the druggability of such class of protein toxins and promoting their in-vivo application for targeted cancer therapy.
SAT0378 Bone marrow oedema and synovitis on MRI of the hand are associate with digital ulcers, active disease and impaired functional capacity in systemic sclerosis
Authors: B Stamenkovic, S Stojanovic, J Nedovic, V Zivkovic, S Milenkovic, J Jovanovic, N Damjanov, A Stankovic
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Hand inflammatory involvement is a major feature in patients with systemic sclerosis (SSc), responsible for major disability. Magnetic resonance imaging (MRI) can identify and characterize subclinical inflammation and joint damage on hand with much greater precision than clinical, radiographic and ultrasonography assessment in SSc. <h3>Objectives</h3> To determine the association of MR bone marrow oedema, synovitis and probability for the occurrence of listed inflammatory changes with clinical features and laboratory tests in SSc patients <h3>Methods</h3> 112 SSc patients were tested (mean age 54y). Contrast enhanced low field MRI of the wrist and MCP2–5 joints was performed to all the pts. MRI bone marrow oedema and synovitis were assessed and scored by OMERACT RAMRIS scoring system. Age, sex, SSc type, disease duration (date of first non Raynaud symptom), Raynaud phenomenon, articular or periarticular pain, joint swelling and contractures, digital ulceration, HAQ, acroosteolysis (by standard PA radiographs of hand and wrist) pulmonary arterial hypertension (PAP&gt;40mmHg at rest on Doppler echocardiography), pulmonary fibrosis (by CT and pulmonary function tests) and laboratory tests (antibody profile, RF, CRP, Creatine phosphokinase) and disease activity (by Valentini index) were done. <h3>Results</h3> By multiple logistic regression analysis taking into account all clinical and laboratory variable, we found that MRI bone marrow oedema of the hand was associated and probability for the occurance of MRI bone marrow oedema was higher for the SSc pts with digital ulcers (OR=6.081;95%IP:1.295–28.550; p&lt;0.05), HAQ&gt;1.5 (OR=6.448; 95%IP: 1.714–24.257; p&lt;0.01) and active disease (OR=3.377; 95%IP; 1.175–9.706; p&lt;0.05). MRI synovitis of the hand was associated and probability for the occurance of MRI synovitis was higher, also, for the SSc pts with digital ulcers (OR=5.128; 95%IP: 1.085–24.243; p&lt;0.05), HAQ&gt;1.5 (OR=9.067; 95%IP: 1.925–42.708; p&lt;0.01) and active disease (OR=3.565; 95%IP: 1.181–10.764; p&lt;0.05). <h3>Conclusions</h3> MRI bone marrow oedema and synovitis on the hand in SSc are associate with digital ulcers, impaired functional capacity and active disease. Monitoring and treatment of clinical features and organ involvement are essential in all the pts with SSc, especially those with proven bone marrow oedema and synovitis on MRI of the hand. <h3>Disclosure of Interest</h3> None declared
FRI0771-HPR Work – related lumbar pain in physiotherapists who work in different fields – a pilot study
Authors: B Karakoç, Z Sarı, O Aydoğdu, US Yurdalan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Having a job exposing the load on the lumbar region increases lumbar pain risk. Lumbar pain takes first place in musculoskeletal disorders among health care workers. A survey which investigated musculoskeletal disorders in physiotherapists indicated that the most common musculoskeletal disorders have seen in the lumbar region. <h3>Objectives</h3> The aim of this study was to determine the work – related lumbar pain in physiotherapists who work in different fields and differences in terms of occupational and personal variables. <h3>Methods</h3> This was a prospective, comparative and multi – central study. Physiotherapists who accepted to participate in this study voluntarily and work at any of paediatric, orthopaedic and neurological fields were received. Eighty – eight physiotherapists were taken first assessment. Their demographic information were taken and they filled out the Oswestry Low Back Disability Questionnaire. Twenty – nine cases who had any orthopaedic disease, surgical history and did not fill the entire of the Oswestry Low Back Disability Questionnaire excluded from the study. Twenty – eight women and 31 men met the criteria for inclusion. Physiotherapists were divided into three groups as paediatric (n=21), orthopaedic (n=24) and neurological (n=14). Lumbar pain level, the number of daily patient transfer, daily working hours and daily standing working hours in three groups were compared. One – way ANOVA was used to compare the groups. SPSS v11.5 was used for the statistical analysis. <h3>Results</h3> There were no significant differences in lumbar pain levels between groups (p=0.342). Daily standing working hours of paediatric group were significantly less than orthopaedic group (p=0.021) and the number of daily patient transfer were significantly higher in paediatric group according to orthopaedic group (p=0.028). Daily standing working hours and the number of daily patient transfer of neurological group had no differences between other groups (p=0.173). <h3>Conclusions</h3> We think that the reason why no differences between the pain level of paediatric and orthopaedic group may be due to more daily transfers in paediatric group and more daily standing working hours in orthopaedic group. The cause why no differences between neurological field and others, might be because of another working factors which we did not assessed. There is a need for research examining in detail on working conditions and trials including more cases. <h3>Disclosure of Interest</h3> None declared
AB0693 Patients with chronic inflammatory arthropathies treated with golimumab achieve a higher serum level of drug if used as the first or second biological drug
Authors: J Rosas, M Marco-Mingot, JM Senabre-Gallego, F Llinares-Tello, A Pons, X Barber, G Santos-Soler, E Salas, C Cano, M Lorente, M Sanchís-Selfa, J Molina, M García-Carrasco
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To know the influence of the order of introduction of Golimumab (GLM), on clinical efficacy in ankylosing spondylitis (AS), psoriatic arthritis (PSA) and rheumatoid arthritis (RA). <h3>Methods</h3> A prospective, observational study, in 46 consecutive patients with AS, APS and RA, treated with GLM. Data: epidemiological, concomitant DMARD, time of disease evolution, HLA-B27, RF and ACPA; from GLM: order of introduction, time in treatment, serum level and anti-GLM Ab. The clinical response was assessed in AS patients using BASDAI, BASFI, ASDAS-VSG. In patients with RA or peripheral APS, DAS28-VSG, DAS28-PCR and SDAI. Serum levels of GLM and anti-GLM Ab were determined by ELISA (Progenika, Grifols SA, Spain). Serum cutoff levels for serum GLM levels: 36 ng/mL and for anti-GLM Ab: UA&gt;20 AU/mL. Samples were extracted just prior GLM administration (trough level) and stored frozen at -80°C until analysis. <h3>Results</h3> Of 33 (72%) AS patients: 52% were males, mean age 53±12 years, mean BMI 28±4, disease mean evolution 16±12 years and in GLM: 1.3±1.1 years, 30% received DMARD, being GLM the first anti-TNF in 25%, second 37%, third 25% and fourth in 13%. The mean GLM level was 0.77±0.62 mg/mL and the prevalence of anti-GLM antibodies was 6%. In the 5 patients with RA and 8 with APS: 23% were men, mean age of 55±11 years, mean BMI 28±6, mean disease evolution of 10.5±8 years and in GLM of 2±1.5 years, the 85% of patients received DMARD, being GLM the first anti-TNF in 31%, second 15%, third 31% and fourth 23%. The mean GLM level was 0.703±0.53 mg/L. No anti-GLM Ab were detected. <h3>Conclusions</h3> 1. The overall prevalence of anti-GLM Ab was 6% and 17% in AS patients. Not detecting in patients with RA or PSA. 2. Serum GLM level was higher among the patients receiving it as the 1st or 2nd anti-TNF. 3. In AS GLM as 3rd or 4th anti-TNF were able to achieve clinical remission, similar to that achieved as 1st or 2nd drug. <h3>Acknowledgements</h3> The study was supported by a grant from the Fundaciόn Española de Reumatología (FVR/2012) and the Asociaciόn para la Investigaciόn en Reumatología de la Marina Baixa (AIRE-MB). <h3>Disclosure of Interest</h3> None declared
Brusatol-Mediated Inhibition of c-Myc Increases HIF-1α Degradation and Causes Cell Death in Colorectal Cancer under Hypoxia
Authors: Eun-Taex Oh, Chan Woo Kim, Ha Gyeong Kim, Jae-Seon Lee, Heon Joo Park
Journal: Theranostics (2017)

HIF-1 (hypoxia-inducible factor-1) regulates the expression of ~100 genes involved in angiogenesis, metastasis, tumor growth, chemoresistance and radioresistance, underscoring the growing interest in targeting HIF-1 for cancer control.In the present study, we investigated the molecular mechanisms underlying brusatol-induced HIF-1α degradation and cell death in colorectal cancer under hypoxia (0.5% O 2 ).Under hypoxia, pretreatment of cancer cells with brusatol increased HIF-1α degradation and cancer cell death in a dose-dependent manner.This effect was mediated by activation of prolyl hydroxylases (PHDs), as evidenced by the block of brusatol-induced HIF-1α degradation and cancer cell death by both pharmacological inhibition and siRNA-mediated knockdown of PHDs.In addition, a ferrous iron chelator (2,2'-bypyridyl) blocked brusatol-induced degradation of HIF-1α and cancer cell death in hypoxia by inhibiting PHD activation.We further found that brusatol inhibited c-Myc expression, and showed that overexpression of c-Myc prevented brusatol-induced degradation of HIF-1α and cancer cell death by increasing mitochondrial ROS production and subsequent ROS-mediated transition of ferrous iron to ferric iron.Consistent with these results, treatment of tumor-bearing mice with brusatol significantly suppressed tumor growth by promoting PHD-mediated HIF-1α degradation.Collectively, our results suggest that brusatol-mediated inhibition of c-Myc/ROS signaling pathway increases HIF-1α degradation by promoting PHD activity and induces cell death in colorectal cancer under hypoxia
FRI0528 Successful implementation of a pharmacist-led fracture liaison service at a us veteran affairs (VA) hospital
Authors: B Buehring, T Holobyn, J Kotek, B Glynn-Servedio, S Wright, K Hansen, A Bridges
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Worldwide, an osteoporosis (OP) care gap exists for individuals with a fragility fracture (FF). Published data shows that US veterans are no exception. To address the OP care gap, fracture liaison services (FLS) are being implemented with the goal to prevent additional FF. <h3>Objectives</h3> Here we report the patient outcomes after initiating a FLS at a US Veterans Affairs (VA) hospital. <h3>Methods</h3> We identified veterans with a pelvic, hip and/or femur shaft fracture by querying a central database. Veterans with traumatic fractures, active OP medication, recent dual-energy X-ray absorptiometry (DXA) and/or hospice status were excluded. The remaining veterans were contacted via letter and the responsible primary health care team was sent a template letter with OP management recommendations via the electronic medical record. Recommendations included DXA, laboratory evaluation, and pharmacologic and non-pharmacologic interventions. In most cases, trained clinical pharmacists serving as FLS coordinators performed all tasks with an expert physician available for questions. Presented data are based on a review 4 months after recommendations were sent. <h3>Results</h3> The initial query revealed 149 veterans with pelvic, femoral, and/or hip fractures without a recent DXA and/or active OP therapy. Of those, 32 (31 males, 1 female) patients suffered a FF and were included in the FLS intervention. Our review showed that 59% of these had a DXA scan, 35% had their calcium/vitamin D intake reviewed, and 40% had started OP therapy or were referred to an OP specialist. When the primary care team9s clinical pharmacist instead of the primary care provider implemented the FLS recommendations (10/32), 100% of the recommendations were addressed. Furthermore, 70% of patients had a bisphosphonate ordered, whereas it was 9% when no pharmacist was involved (p=0.0004). <h3>Conclusions</h3> Our study suggests that a pharmacist-led FLS improves post-FF care in US veterans. We found a high percentage of OP care goals met when patients interacted with clinical pharmacists. This observation might be due to the fact that most pharmacists had dedicated training in OP management and their interaction with the patient focused on their FF. In summary, our data suggests that clinical pharmacists trained in OP management can very effectively implement a FLS intervention. <h3>Disclosure of Interest</h3> None declared
Synergistic effects of dendritic cell targeting and laser-microporation on enhancing epicutaneous skin vaccination efficacy
Authors: Yoan Machado, Sanne Duinkerken, Veronika Hoepflinger, Melissa Mayr, Evgeniia Korotchenko, Almedina Kurtaj, Isabel Pablos, Markus Steiner, Angelika Stoecklinger, Joyce Lübbers, Maximillian Schmid, Uwe Ritter, Sandra Scheiblhofer, Michael Ablinger, Verena Wally, Sarah Hochmann, Anna M. Raninger, Dirk Strunk, Yvette van Kooyk, Josef Thalhamer, Richard Weiss
Journal: Journal of Controlled Release (2017)