tbuckley/cabot-search huggingface dataset:
Abstract 15194: Age May Be a Better Predictor Than Gender of Atypical ST-Elevation Myocardial Infarction Presentation
Authors: Tyson G Taylor, Ronald E Stickney, William J French, Nichole Bosson, James G Jollis, Michael C Kontos, Stephen G Sanko, Marc K Eckstein
Journal: Circulation (2017)

Widespread use of field 12-lead ECG to screen for STEMI can lead to low positive predictive value of software interpretations and resultant false-positive STEMI alerts. One solution is to limit 12-...
Farm-like indoor microbiota in non-farm homes protects children from asthma development
Authors: Pirkka V. Kirjavainen, Anne M. Karvonen, Rachel I. Adams, Martin Täubel, Marjut Roponen, Pauli Tuoresmäki, Georg Loss, Balamuralikrishna Jayaprakash, Martin Depner, Markus Johannes Ege, Harald Renz, Petra Ina Pfefferle, Bianca Schaub, Roger Lauener, Anne Hyvärinen, Rob Knight, Dick J. J. Heederik, Erika von Mutius, Juha Pekkanen
Journal: Nature Medicine (2019)
AB0123 CCL17 IN SYNOVIAL FLUID AND PLASMA OF PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS
Authors: Cecil Hor, Adrian Achuthan, Keith Lim, John Hamilton
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Despite the advancements in management of rheumatoid arthritis (RA) in the last two decades, there are still a significant number of patients who cannot achieve low disease states or remission with the current available therapy. Granulocyte macrophage-colony stimulating factor (GM-CSF) is a key mediator in inflammation and autoimmunity, and has emerged as a novel therapeutic target in RA. However, potential adverse side effects warrant further investigation of a more specific target. <h3>Objectives</h3> Chemokine (C-C motif) ligand 17 (CCL17) is a downstream mediator of GM-CSF and has recently been shown to be regulated by GM-CSF in human monocytes. Significantly, CCL17 has a non-redundant role in inflammatory arthritis and pain. We investigated the expression levels of CCL17 in synovial fluid and plasma from RA patients. <h3>Methods</h3> We recruited RA patients with symptomatic swollen joints, who require joint aspiration for diagnostic and/or therapeutic purposes. Synovial fluid and plasma were collected and CCL17 protein levels were determined by ELISA. <h3>Results</h3> CCL17 protein was measured in synovial fluid and plasma samples from our cohort of RA patients. Levels of secreted CCL17 were higher in plasma [median 240 (40-580) pg/ml] compared to synovial fluid [median 100 (30-300) pg/ml] p&lt;0.05. <h3>Conclusion</h3> Significant levels of CCL17 were detected in RA synovial fluid and plasma. This is a novel study which demonstrates and compares the presence of CCL17 in synovial fluid and plasma from matching RA patients. The expression of CCL17 in plasma can make it a useful potential biomarker for RA, while its expression in synovial fluid suggests that CCL17 may be a therapeutic target for treating RA. <h3>References</h3> [1] Gibofsky, A., Epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis: A Synopsis. Am J Manag Care, 2014. 20(7Suppl): p. S128-35. [2] Hamilton, J.A., GM-CSF as a target in inflammatory/autoimmune disease: current evidence and future therapeutic potential. Expert Rev Clin Immunol, 2015. 11(4): p. 457-65. [3] Achuthan, A., et al., Granulocyte macrophage colony-stimulating factor induces CCL17 production via IRF4 to mediate inflammation. J Clin Invest, 2016. 126(9): p. 3453-66. <h3>Disclosure of Interests</h3> Cecil Hor Speakers bureau: Mundipharma, Pfizer, Adrian Achuthan: None declared, Keith Lim Consultant for: Advisor for role of hepatitis and TB in Cimzia, UCB, Speakers bureau: Role of biological in pregnancy UCB, John Hamilton Grant/research support from: GSK
Abstract 13330: Depression is Associated With Cardiovascular Events in Male but Not Female Patients With One or More Cardiovascular Risk Factors: Japan Morning Surge Home Blood Pressure (J-HOP) Study
Authors: Tomoyuki Kabutoya, Satoshi Hoshide, Kazuomi Kario
Journal: Circulation (2015)

Introduction: Depression is associated with cardiovascular events, and the frequency of depression is higher in females than in males. However, the association between depression and cardiovascular events in patients with cardiovascular risk factors and the gender difference of the association remains unclear. Hypothesis: We assessed the hypothesis that depression was associated with a poor prognosis in patients with cardiovascular risk factors, and that the association is different in males and females. Methods: We enrolled 3,216 patients in the Japan Morning Surge Home Blood Pressure Study who had one or more cardiovascular risk factors. We conducted the Beck Depression Inventory (BDI). Depression was defined as having a BDI score ≥ 16. The primary endpoints were fatal/nonfatal cardiovascular events (myocardial infarction, stroke, hospitalization for heart failure, aortic dissection). Results: The mean follow-up period was 47±24 months, and 134 patients suffered primary endpoints. In male patients, depressive patients (N=184) were more likely to suffer cardiovascular events than non-depressive patients (N=1439) (log rank 6.79, p=0.009). In female patients, cardiovascular events were similar in depressive (N=347) and nondepressive patients (N=1246,log rank 0.06, p=0.81). A Cox proportional hazards model including age, history of hypertension, dyslipidemia and diabetes revealed that depression was a significant, independent predictor of primary endpoints in male patients (hazard ratio 2.01, 95% confidence interval 1.20-3.37, p=0.008). Conclusions: Depression is associated with cardiovascular events in male but not female patients with one or more cardiovascular risk factors.
A randomized trial to determine if vitamin B6 can prevent hand and foot syndrome in cancer patients treated with capecitabine chemotherapy.
Authors: Tareq Braik, Barbara Yim, Arthur T Evans, Mohammed Azher Kassem, Tycel Jovelle Phillips, Michael Russell Mullane, Thomas E. Lad, Lily Hussein, Barbara Cleveland, Susan H. McDunn
Journal: Journal of Clinical Oncology (2012)

9085 Background: Capecitabine is an oral fluoropyrimidine that is used to treat various malignancies. Hand and Foot Syndrome (HFS) is a dose limiting toxicity of capecitabine and can limit the use of this agent in some patients. Some investigators have observed that pyridoxine (vitamin B6) can ameliorate HFS caused by capecitabine. We designed a prospective trial to determine if pyridoxine can prevent HFS in patients receiving capecitabine. Methods: In our double-blind, placebo controlled trial, we randomly assigned eligible patients treated with capecitabine to receive either daily pyridoxine 100 mg or placebo along with their capecitabine-containing chemotherapy regimen. Patients were observed during the first four cycles of capecitabine treatment. The primary end point was the incidence and grade of HFS that occurred in both arms. Results: Between 2008 and 2011, 77 patients were randomly assigned to receive either pyridoxine (n=38) or placebo (n=39). Both arms were matched in baseline characteristics. The median age was 53.5 years. The ethnic composition of the study population was African American 53%, Caucasian 22%, Hispanic 18%, and Asian 7%. The daily doses of capecitabine were: 2000 mg/m2 (69 pts), 1650 mg/m2 (5 pts), 1400 mg/m2 (2 pts) and 1000 mg/m2 (1 pt). Dosages of capecitabine were equally matched between the two arms of the study. HFS occurred after a median of 2 chemotherapy cycles in both groups. HFS developed in 10/38 (26%) patients in the pyridoxine group and in 8/39 (20%) patients in the placebo group (p=0.547). Therefore, the risk of HFS was 6 percentage points higher in pyridoxine group (95% CI for difference: -13 percentage points to +25 percentage points). Given our study results, we can be confident of excluding a true benefit from pyridoxine larger than 13 percentage points. No difference in HFS grades was observed. Conclusions: Prophylactic pyridoxine (vitamin B6), given concomitantly with capecitabine-containing chemotherapy, was not effective for the prevention of HFS. [Table: see text]
AB0896 REINFECTION OF PROSTHETIC JOINT WITH A DIFFERENT MICROORGANISM: A PROSPECTIVE COHORT STUDY
Authors: Caroline Beal, Valerie Zeller, Younes Keroumi, Vanina Meyssonnier, Beate Heym, Pascal Chazerain, Simon Marmor
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Treatment failure of prosthetic joint infection (PJI) may be due to relapsing infection (with the same microorganism) or a new infection (with a different microorganism). Data on new prosthetic joint infections (NPJI) are scarce, although they represent a devastating complication and a therapeutic challenge of joint arthroplasty. <h3>Objectives</h3> The aim of this study was to describe epidemiological, clinical and microbiological characteristics of NPJI, their treatment and outcome. <h3>Methods</h3> This observational single-center cohort study was conducted in a French referral center for bone and joint infections. All patients admitted between January 2000 and December 2015 with a documented hip or knee PJIs and at least 2 years of follow-up, were identified. Among those, all patients treated in our center for at least two successive PJIs, involving the same joint and due to different microorganisms, were included. We compared these patients with a random selection of 124 "single"-PJIs (72 knee and 52 hip prostheses) treated in our center and followed at least 2 years. <h3>Results</h3> Among 909 PJIs treated during the study period, 62 patients with 70 NPJIs were included (7.7%) NPJIs developed more frequently in knee (15.7%) than in hip prostheses (4.4%) (p&lt;0.001). Median [range] age was 70 [66-80] years old and median [range] body mass index was 28.7 [25-33] kg/m<sup>2</sup>. Median [range] duration from the first to the NPJI was 16 months [0-98]. Hematogenous spread of the infection was quite higher in NPJIs compared to single-PJIs (92% versus 31% (p=0.0001). NPJIs were predominantly monomicrobial (82%), due to <i>S. aureus</i> (29%), <i>Streptococcus</i> sp. (29%) <i>Gram-negative bacilli</i> (11%) or others (31%). A curative strategy was applied to 71% of the patients with a NPJI: DAIR (31%), 1-stage exchange arthroplasty (24%), 2-stage exchange arthroplasty (5%) and other strategies (11%). For the other patients, prolonged suppressive antibiotic therapy was prescribed (29%), combined with surgery in 10% of patients. Eight patients had a second NPJI, 6 were an acute hematogenous PJI. Four risk factors for NPJI were identified by multivariate analysis : chronic dermatitis (odds ratio [OR] 11.49; 95% CI,2.40,55.01; p=0.002), 2-stage exchange arthroplasty during the first PJI (OR 6.99; 95% CI,2.83, 17.27; p=0.0001), high blood pressure (OR 3.17; 95% CI,1.39, 7.20; p=0.006) and male gender (OR 2.99;95% CI,1.35, 6.60; p=0.007). <h3>Conclusion</h3> NPJIs are complex PJI affecting more frequently the knee prostheses. They occur predominantly via hematogenous spread from a distant infectious focus, especially the skin. In these complex settings, management by multi-disciplinary teams, should be adapted to each clinical situation. <h3>Disclosure of Interests</h3> None declared
SAT0189 A NOVEL DEVICE FOR RAPID MINOR SALIVARY GLAND BIOPSY IN SUSPECTED SJÖGREN’S SYNDROME
Authors: Alexandre Dumusc, Bettina Bannert, Diana Dan, Thomas Huegle
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Labial minor salivary glands (MSG) biopsies are a frequently performed diagnostic procedure for Sjögren's syndrome. MSG biopsy usually requires additional assistance e.g. to provide lower lip protrusion and to apply pressure on the lip during the procedure. The latter is done to foster protrusion of salivary glands and therefore to reduce the incision depth and potential nerve damage. We recently developed a new single-use device for MSG by 3D-printing in form of a lip clamp with a stamp on the lower arm to reduce invasiveness and to facilitate the intervention. <h3>Objectives:</h3> To assess practicability and to describe the technical application of this device for MSG biopsies in the rheumatology department. <h3>Methods:</h3> Retrospective study of MSG biopsies performed with the use of a dedicated lip clamp. For each MSG biopsy, we recorded if any assistance was needed during the procedure, occurrence of any complication, if salivary glands were obtained and if the quality of the salivary gland tissue sample was adequate for histologic analysis. <h3>Results:</h3> 12 MSG biopsies performed on 12 patients with suspected Sjögren's syndrome were included in the study. MSG biopsies were performed between August 2018 and January 2019. Using the lip clamp, the physician was able to perform all the biopsies without assistance. No complication occurred with a follow-up of 1 week for each patient. Salivary glands tissue samples were obtained in 11/12 of the patients using 1 incision. For 1 patient, a second incision had to be performed on the contralateral side of the lip during the same intervention because no glands were found on the first attempt. Quality of all the samples was adequate for histologic analysis. We did not observe an increase in procedure time compared to routine MSG biopsy procedure. <h3>Conclusion:</h3> The use of a single-use lip clamp facilitates MSG biopsy without needing assistance and potentially reduces invasiveness and collateral damage. Quality of the tissue samples obtained was adequate for histological analysis. <h3>Disclosure of Interests:</h3> Alexandre Dumusc: None declared, Bettina Bannert: None declared, Diana Dan: None declared, Thomas Huegle Grant/research support from: AbbVie, Lilly, Novartis and Pfizer, Speakers bureau: AbbVie, Lilly, Novartis and Pfizer
Immune checkpoint inhibitors in the treatment of virus-associated cancers
Authors: Peipei Gao, Cordelle Lazare, Canhui Cao, Yifan Meng, Ping Wu, Wenhua Zhi, Shitong Lin, Juncheng Wei, Xiaoyuan Huang, Ling Xi, Gang Chen, Junbo Hu, Ding Ma, Peng Wu
Journal: Journal of Hematology & Oncology (2019)

Among all malignant tumors that threaten human health, virus-related tumors account for a large proportion. The treatment of these tumors is still an urgent problem to be resolved. The immune system is the "guard" of the human body, resisting the invasion of foreign substances such as viruses. Studies have shown that immunotherapy has clinical significance in the treatment of a variety of tumors. In particular, the emergence of immune checkpoint inhibitors (ICIs) in recent years has opened a new door to cancer therapy. Considering the potential role of ICIs in the treatment of virus-related cancers, we focused on their therapeutic effect in virus-associated cancers and explored whether the therapeutic effect in virus-associated cancers was related to virus infection status. Although there is no clear statistical significance indicates that ICIs are more effective in virus-associated cancers than non-virus infections, the efficacy of checkpoint inhibitors in the treatment of virus-related cancers is promising. We believe that this research provides a good direction for the implementation of individualized precision medicine.
SAT0153 1,25(OH)2D AND IL-6 BLOCKADE SYNERGISTICALLY REGULATES RHEUMATOID ARTHRITIS VIA SUPPRESSION OF TH17 AND OSTEOCLASTOGENESIS
Authors: Moon Young Kim, Jennifer Lee, Sung-Hwan Park
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Immune cells express vitamin (vit) D receptor and vit D is known as a potent immune-modulator. <h3>Objectives</h3> Based on negative association of serum vit D level with rheumatoid arthritis (RA) disease activity on previous studies, we aimed to evaluate the role of the vit D in treatment response in RA patients on anti-IL-6 receptor antibody – tocilizumab. <h3>Methods</h3> RA patients on tocilizumab were enrolled, and data were collected retrospectively. Disease activity (disease activity score (DAS) 28), serum 25(OH)D level, modified Sharp's score of hand x-ray at the time of tocilizumab initiation and follow up were analyzed. Peripheral blood mononuclear cells (PBMCs) were differentiated into Th17 or osteoclast in the presence or absence of various concentrations of tocilizumab and/or 1,25(OH)<sub>2</sub>D. Proportion of Th17 was analyzed by FACS. <h3>Results</h3> Among 98 RA patients on tocilizumab, 34 (34.7%) patients had sufficient serum 25(OH)D level (≥30ng/mL) when tocilizumab was initiated. On 24 weeks, DAS 28 reduction was greater (64.6 ± 15.5% vs. 52.7 ± 20.7%, P=0.004) and more patients achieved low disease activity (91.2% vs. 70.3%, P=0.018) or remission (82.4% vs. 57.8%, P=0.014) in vit D sufficient group. On 48 weeks, DAS28 reduction and proportion of patients with remission was greater in vit D sufficient group as well. However, there was no significant difference in hand &amp; wrist erosion progression. In vitro, tocilizumab and active vit D 1,25(OH)<sub>2</sub>D treatment synergistically suppressed Th17 differentiation and osteoclastogenesis from PBMC. <h3>Conclusion</h3> RA patients being treated with IL-6 blocker show better response when they have sufficient serum vit D level. Active vit D seems to suppress Th17 and osteoclasts differentiation in RA patients in synergy with tocilizumab. <h3>Reference</h3> [1] Bellan M. Role of Vitamin D in Rheumatoid Arthritis. Adv Exp Med Biol. 2017;996:155-168 <h3>Disclosure of Interests</h3> None declared
An ordinal model to predict the risk of symptomatic liver failure in patients with cirrhosis undergoing hepatectomy
Authors: Mathieu Prodeau, Elodie Drumez, Alain Duhamel, Eric Vibert, Olivier Farges, Guillaume Lassailly, Jean-Yves Mabrut, Jean Hardwigsen, Jean-Marc Régimbeau, Olivier Soubrane, René Adam, François-René Pruvot, Emmanuel Boleslawski
Journal: Journal of Hepatology (2019)
Abstract 18848: Weight Gain is Not a Significant Predictor of Coronary Artery Disease Severity
Authors: Christopher J Franzese, Kevin P Bliden, Tania B Gesheff, Cescelle B Barbour, Martin G Gesheff, Peter P Toth, Udaya Tantry, Paul A Gurbel
Journal: Circulation (2014)

Background: Obesity, along with hypertension and diabetes, is a known risk factor for coronary artery disease (CAD). Recent studies have proposed that obese individuals may actually experience less adverse cardiovascular outcomes and mortality compared to non-obese individuals, a phenomenon known as the “obesity paradox”. We sought to determine if weight gain is associated with overall CAD severity measured by coronary angiography. Methods: Suspected CAD patients (n=418) were enrolled in the Multi-Analyte, Thrombogenic, and Genetic Markers of Atherosclerosis (MAGMA) study prior to elective cardiac catheterization. Demographics and weight information were obtained, and maximum weight gain (MWG) was defined as the percent increase in weight from year of high school graduation to year of heaviest weight. Subjects were divided into the following quartiles based on MWG: none (≤30%), minor (31%-47%), major (48%-69%), and extreme (≥70%). Detailed lipid profiling was determined by vertical density gradient ultracentrifugation, thrombin-induced platelet fibrin clot strength (TIP-FCS) by thromboelastography, and urinary 11-dehydrothromboxane B2 (11-dhTxB2) by ELISA. Severity of CAD was defined as none/minimal (&lt;20%), moderate (20-75%), and severe (75%) luminal diameter obstruction of any major coronary vessel. Results: The average MWG in the study population was 53 ± 33%. Patients in the extreme MWG group had the highest incidence of DM (47.5%), hypertension (80.8%), and depression (25.3%), and were most often female (59.6%). There was an inverse relationship between MWG and CAD severity (p=0.005)(figure). TIP-FCS increased in a stepwise fashion with MWG (p=0.001). 11-dTxB2 and triglyceride levels were significantly higher in the extreme MWG group, regardless of cholesterol lowering therapy (p&lt;0.05 for all). Conclusion: Our data suggest that weight gain is associated with heightened thrombotic risk but not an increased risk for CAD.
Abstract 408: Spliced X-box Binding Protein 1 Promotes Cardiac Hypertrophy through Activation of mTORC1
Authors: Xiaoding Wang, Jianping Li, Diem Hong Tran, Lin Xu, Thomas G Gillette, Xuejun Jiang, Zhao V Wang
Journal: Circulation Research (2017)

Background: Spliced X-box binding protein 1 (Xbp1s) is a key signal transducer and the most conserved branch of the unfolded protein response (UPR). Its role in cardiac hypertrophy and heart failure however remains poorly understood. Aims: To explore the role of Xbp1s in the development of pathological cardiac hypertrophy and remodeling. Methods and Results: Here, we showed that the expression of Xbp1s was highly and acutely induced by pressure overload in mouse hearts. Transgenic overexpression of Xbp1s in vivo led to cardiac hypertrophy, and exacerbated the hypertrophic response in response to transverse aortic constriction. At the mechanistic levels, we found that FK506 binding protein 11 (Fkbp11) is a bona fide transcriptional target of Xbp1s. Overexpression of Xbp1s stimulated Fkbp11 at both in vitro and in vivo levels. In so doing, Xbp1s directly augmented the mTORC1 signaling, the master regulator of cell growth. Indeed, siRNA-mediated knockdown of Fkbp11 significantly diminished Xbp1s-induced mTORC1 activation and hypertrophic growth in cardiac myocytes. Conclusions: Our results uncovered a novel link between protein-folding and cell growth with Xbp1s, Fkbp11 and mTORC1 as the key mediators, which may provide insights about our understanding of pathological cardiac remodeling in pressure overload.
Uniparental Inheritance Promotes Adaptive Evolution in Cytoplasmic Genomes
Authors: Joshua R. Christie, Madeleine Beekman
Journal: Molecular Biology and Evolution (2016)

Eukaryotes carry numerous asexual cytoplasmic genomes (mitochondria and plastids). Lacking recombination, asexual genomes should theoretically suffer from impaired adaptive evolution. Yet, empirical evidence indicates that cytoplasmic genomes experience higher levels of adaptive evolution than predicted by theory. In this study, we use a computational model to show that the unique biology of cytoplasmic genomes—specifically their organization into host cells and their uniparental (maternal) inheritance—enable them to undergo effective adaptive evolution. Uniparental inheritance of cytoplasmic genomes decreases competition between different beneficial substitutions (clonal interference), promoting the accumulation of beneficial substitutions. Uniparental inheritance also facilitates selection against deleterious cytoplasmic substitutions, slowing Muller’s ratchet. In addition, uniparental inheritance generally reduces genetic hitchhiking of deleterious substitutions during selective sweeps. Overall, uniparental inheritance promotes adaptive evolution by increasing the level of beneficial substitutions relative to deleterious substitutions. When we assume that cytoplasmic genome inheritance is biparental, decreasing the number of genomes transmitted during gametogenesis (bottleneck) aids adaptive evolution. Nevertheless, adaptive evolution is always more efficient when inheritance is uniparental. Our findings explain empirical observations that cytoplasmic genomes—despite their asexual mode of reproduction—can readily undergo adaptive evolution.