tbuckley/cabot-search huggingface dataset:
Abstract 413: Podoplanin Neutralization Improves Cardiac Remodeling and Function After Acute Myocardial Infarction
Authors: Maria Cimini, Venkata N Garikipati, Suresh K Verma, Cindy Benedict, Zhongjian Cheng, Claudio de Lucia, Chunlin Wang, Anna Maria Lucchese, David Goukassian, Raj Kishore
Journal: Circulation Research (2017)

Variety of cardioprotective and reparative therapeutic approaches have emerged for the treatment of cardiac remodeling after myocardial infarction (MI). Here we propose a novel mechanism using a neutralizing antibody that target Podoplanin (PDPN), a platelet aggregation-inducing type I transmembrane glycoprotein, expressed on a cohort of myocardial cells that migrate to the infarcted area after MI and contribute significantly to scar formation. The PDPN+ cells were isolated from infarcted hearts two days after MI, using magnetic beads sorting. We tested in vitro the effect of PDPN neutralizing antibody (5μg/ml) in a transwell migration assay and the activation of monocytes co-cultured with PDPN+ cells. The neutralizing antibody decreased significantly PDPN+ cells migration. Monocytes co-cultured with PDPN+ cells produced high levels of IL1α and IL12, whereas treatment of co-cultures with podoplanin neutralizing antibody inhibited IL1α and IL12 production and increased IL9 and IL10 production, suggesting a switch form pro-inflammatory to anti-inlammatory phenotype. To tests the effect of podoplanin neutralizing antibody in vivo, C57BL/6 wild type mice were subjected to experimental MI and anti-PDPN antibody (25μg/ml) was injected i.p. on days 1, 2, 7 and 15 after MI and mice were scarified two months after. At 7 days after MI echocardiography revealed comparable ~30% of ejection fraction (EF) in control and antibody-injected mice. After one month EF% remained unchanged in control group and increased up to 45% in antibody-treated group, suggesting improvement in cardiac function. Histologically, in the control group the ischemic area was composed by fibrotic tissue highly positive for fibronectin and αSMA, whereas in the antibody-treated group revealed large number of survived, as well as proliferating myocytes expressing αSARC-actin and Phospho-H3. Further, there was a significant increase in CD31 positive cells in the infarct border-zone of antibody-treated vs. control hearts, suggesting increased angiogenesis. Our findings suggest that inhibition of PDPN during first two weeks after MI intensely enhances cardiac regeneration and angiogenesis. This may represent a new therapeutic support for the tissue renewal after MI.
AB0848 BMD AND MUSCLE MASS IN PATIENTS WITH ISCHEMIC HEART DISEASE
Authors: Tatiana Raskina, Inessa Grigoreva, Olga Barbarash, Alexander Kokov, Vladislava Masenko
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Mounting biological and epidemiological evidence supports a link between the ischemic heart disease (IHD) and osteoporosis (OP), but the studies investigating muscle mass and its relationship with OP in patients with IHD are limited. <h3>Objectives</h3> The aim of this study is to investigate the relationship between OP and muscle mass in patients with IHD. <h3>Methods</h3> The study included 45 patients with IHD (36 males/9 females, mean age 63,16±6,71 years) verified by coronary angiography. BMD was measured by DXA in the the lumbar spine L1-L4, total hip and femoral neck. BMD was evaluated as: normal BMD (T-score ≥-1), osteopenia (T-score between -1 and -2.5) and osteoporosis (T-score of &lt;-2.5). Muscle mass was assessed using computed tomography of total psoas area (TPA) (cm2) and calculating L3 muscle index (LMI) (&lt;52,4 cm2/m2 in men; &lt;38,5 cm2/m2 in women). <h3>Results</h3> The results of densitometry patients were distributed as follows: 30 patients (66,6%) with normal BMD, 12 (26,6%) with osteopenia and 3 (0.66%) with osteoporosis. Patients was divided into 2 groups: 1) nonosteopenia-nonOP and 2) osteopenia/OP. Mean femoral neck BMD was 1,024±0,09 g/cm2 and 0,809±0,06 g/cm2, respectively. L1-L4 BMD was 1,260±0,14 g/cm2 for normal BMD group and 1,154±0,16 for osteopenic/OP group. Patients with osteopenia/OP had statistically significant lower LMI (45,57±4,66 cm2/m2 vs. 52,78±10,24 cm2/m2, p=0,01 for low femoral neck BMD; 46,33±6,97 cm2/m2 vs. 52,76±6,74 cm2/m2, p=0,02 for low L1-L4 BMD, respectively). According to the correlation analysis a positive relationship between L1-L4 BMD and LMI was revealed (r=0,373, p&lt;0,05). There was no correlation between femoral neck BMD and LMI (r=0,272, p=0,274). <h3>Conclusion</h3> The decline in BMD in IHD patients is associated with low muscle mass and correlated with severity of BMD dissension in the lumbar spine, but not in the neck of the femur. The obtained results confirm high probability of existence of common pathogenetic links between OP and sarcopenia. <h3>Disclosure of Interests</h3> None declared
THU0068 ANTI-CARBAMYLATED ANTIBODIES ARE ASSOCIATED WITH TOBACCO AND POOR OUTCOMES IN RHEUMATOID ARTHRITIS
Authors: Raul Castellanos-Moreira, Sebastian C Rodriguez-García, Virginia Ruiz, Oscar Camacho, Julio Ramirez, Andrea Cuervo, Cristina Garcia-Moreno, Rosa Morla, José Gomez Puerta, Juan D. Cañete, Isabel Haro, Raimón Sanmartí
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Anti-carbamylated protein antibodies (Anti-CarP) represent a novel autoantibody family present in sera of patients with rheumatoid arthritis (RA) with high specificity. <h3>Objectives:</h3> To analyse the prevalence of Anti-CarP in an established RA cohort and evaluate their association with the presence of other autoantibodies and disease activity and severity. <h3>Methods:</h3> Cross-sectional study. Presence of Anti-CarP was analyzed in a cohort of patients with established RA (n: 158) by a home-made ELISA test using fetal calf serum. We investigated the demographic, radiological and current and at disease onset clinical features. Rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) status were also assessed. <h3>Results:</h3> Anti-CarP were positive in 46.2% of the patients in our cohort and in 15.1%, 19.2% and 9.1% of the patients negative for ACPA, RF and both respectively. Demographic and clinical features are shown in table 1. The mean titer of ACPA (1361±1054 U/mL vs. 918 ± 1092 U/mL) and RF (258 ± 255 AU vs. 174 ± 205 AU) were significantly higher in Anti-CarP positive patients. No difference in symptoms at RA onset was observed. Current (24.7% vs. 11.8%) and previous (54.8% vs. 37.6%) smoking consumption were significantly associated with Anti-CarP antibodies. Anti-CarP positive patients presented a higher CRP values (1. 0±1.6 mg/dL vs. 0.5 ±0.8 mg/dL), swollen joint count (1.3±2.2 vs 0.7 ±1.8) and patient global health assessment VAS (34.8 ±21.5 mm vs. 26.4 ±17.1 mm); although no between-group differences in disease activity (DAS28, CDAI, SDAI and RAPID3) or demographic features were observed. Anti-CarP positive patients presented significant higher scores in Larsen index (23.6 ± 15.7 vs. 15.7 ± 12.6) and disability (HAQ-DI &gt;1) (23.3% vs. 8.3%). <h3>Conclusion:</h3> Anti-CarP were present in approximately half of the RA cohort and were also detected in seronegative (RF and/or ACPA) patients. In our cohort, patients with Anti-CarP antibodies presented higher tobacco consumption and poorer disease outcomes. <h3>Disclosure of Interests:</h3> Raul Castellanos-Moreira Speakers bureau: For Lilly and Merk Sharp and Dohme, Sebastian C Rodriguez-García: None declared, Virginia Ruiz: None declared, Oscar Camacho: None declared, Julio Ramirez: None declared, Andrea Cuervo: None declared, Cristina Garcia-Moreno: None declared, Rosa Morla: None declared, José Gomez Puerta Speakers bureau: BMS, Pfizer, Amgen, Juan D. Cañete: None declared, Isabel Haro: None declared, Raimón Sanmartí Speakers bureau: PFIZER, SANOFI, LILLY, MSD, UCB, NOVARTIS, JANSSEN
FRI0702-HPR NON PHARMACOLOGICAL MANAGEMENT OF FIBROMYALGIA: A SYSTEMATIC REVIEW OF SYSTEMATIC REVIEWS
Authors: Pamela Andrews, Lorna Paul, Martijn Steultjens
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Despite the number of guidelines and available therapies, many individuals with fibromyalgia (FM) still experience significant pain and a reduced quality of life. Patient heterogeneity and clinical uncertainty can lead to delays in selecting the most appropriate management strategy. There are more than 300,000 publications surrounding the management of FM, thus affecting clinicians' ability to make informed decisions. The systematic review of randomised controlled trials is the gold standard in evaluating an intervention. However, the increase in systematic reviews (SRs) has led to some questions regarding their quality. Therefore there is a need to synthesise the evidence with an overview of SRs. <h3>Objectives</h3> To evaluate the quality of the current evidence from SRs on the effects of non-pharmacological interventions for the management of FM. <h3>Methods</h3> A systematic search of seven databases (1990-2018) was completed to identify SRs reporting the effects of non-pharmacological interventions on the primary outcomes of pain, function and quality of life (QoL). Data was extracted according to the PICO framework in addition to intervention prescription where appropriate. Methodological quality was assessed using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR-2) instrument (Shea et al 2017). <h3>Results</h3> Twenty-six SRs with 243 primary studies met the inclusion criteria. Reviews were classified into 6 categories (1) land-based exercise; (2) water-based exercise; (3) mind-body; (4) electrotherapy; (5) manual therapy and (6) complementary and alternative medicine (CAM). Quality of the included SRs were variable with many interventions scoring low to critically low. High quality evidence was found to support the use of land-based exercise and mind-body therapies for the improvement of pain, function and QoL (Table). In particular aerobic exercise with or without strength training and mind-body therapies demonstrated the best outcome. <h3>Conclusion</h3> With the exception of land-based exercise and mind-body exercise, the quality of evidence for the non-pharmacological management of FM is mostly poor, with more than half of the included reviews scoring low or critically low on the AMSTAR-2 instrument. Improved reporting of outcome data and stricter methodological quality will allow stronger recommendations in the future. <h3>References</h3> [1] Shea, B.J., et al., AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. bmj, 2017. 358: p. j4008 0959-8138. <h3>Disclosure of Interests</h3> None declared
Abstract 19: State-level Disparities in Health Loss Due to Cardiovascular Causes: Results of the Global Burden of Disease 2015 Study
Authors: Gregory A Roth, Catherine O Johnson, Nicholas J Kassebaum, Ali H Mokdad, Mohsen Naghavi, Theo Vos
Journal: Circulation (2017)

Introduction: Reducing cardiovascular (CVD) health disparities is a major policy goal in the United States but comprehensive and comparable estimates of CVD disease burden do not exist. The GBD2015 study developed a method to estimate disability-adjusted life-years (DALYs) lost to CVD for each state. Hypothesis: We assessed the hypothesis that health loss due to CVD is no longer declining in the United States. Methods: We used death certificates, health surveys, commercial databases, and published literature to estimate CVD death rate and prevalence. Our analyses corrected for use of non-specific causes of death, readmission rates, and variation in the use of ICD codes. Models were run separately by age, sex, state, cause, and year. Disability weights were derived from large-scale surveys of the public. Uncertainty intervals (UI) were estimated using 1000 draws from the posterior distribution of each model. Results: In the U.S. in 2015, 13.63 million DALYs were lost due to CVD (95% UI 13.1-14.2), which accounted for 15.4% (95% UI 14.1-16.9%) of total DALYs for the United States. From 1990-2015, the annualized rate of change for CVD DALYs (per 100,000 persons) was -1.2%, but for 2010-2015, this rate was 0.5%. The smallest annualized rate of change for CVD DALYs (per 100,000, age-standardized) from 1990-2015 was observed in Oklahoma (-1.1%) while the largest change was in New York (-2.6%). For only 2010-2015, this rate declined in most states but increased in Idaho, Indiana, Mississippi, and Maine by 0.02-0.47%. Ischemic heart disease was the predominant cause of health loss for all states. Conclusions: The decline in CVD burden has slowed in all states, with rates rising in several states. Further efforts are needed to understand state-level factors influence changing rates of CVD burden.
FRI0223 EXTRACELLULAR VESICLESAS A SOURCE OF BIOMARKERS IN SJöGREN SYNDROME: A SWATH-MS PROTEOMIC APPROACH
Authors: Chiara Baldini, Francesco Finamore, Francesco Ferro, Marta Mosca, Stefano Bombardieri, Silvia Rocchiccioli, Antonella Cecchettini
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Primary Sjögren's syndrome (pSS) is a multifactorial autoimmune disorder characterized by lymphocytic infiltration of the exocrine glands. In the recent past several proteomic studies attempted to look at valid biomarkers for pSS in whole saliva, however little is known about the composition of salivary extracellular vesicles (EVs), nor to what extent their content may reflect the phenotypic state of the disease. <h3>Objectives:</h3> In this study, we search for pSS specific biomarkers by using a sequential window acquisition of all the theoretical fragment ion spectra (SWATH-MS) approach to monitor the dynamics of saliva EVs sub-proteome of pSS patients compared to healthy controls. <h3>Methods:</h3> We included patients with a diagnosis of pSS made according to the AECG 2002 criteria and healthy volunteers as controls. Saliva was collected under standardized conditions. EVs were enriched by sequential ultracentrifugation steps from saliva samples. Peptide identification and quantitation was performed by matching SWATH data against an assay library of MS/MS spectra created from a previously acquired data-dependent acquisition (DDA) method. GO terms and protein-protein interaction network analysis were performed using Cytoscape software. <h3>Results:</h3> We included 20 pSS patients (AECG 2002 criteria) and 10 healthy subjects. Quantitative data evidenced a distinct separation between the patient group and control group, indicating that pSS may modulate the phenotype of protein cargoes of salivary EVs. The majority of the proteins up-regulated in pSS compared to controls were found to be involved in several inflammatory processes. Particular emphasis was given to proteins converging to IL-12 signaling that included annexin A2, cofilin, macrophage migration inhibitory factor (MIF), S100A8-A9 and plastin-2 proteins. <h3>Conclusion:</h3> Our results revealed that the inflammatory phenotype observed in pSS patients is also extended to salivary EVs, which protein content may represent a novel source for potentially useful biomarkers for pSS. <h3> Disclosure of Interests: </h3> Chiara Baldini: None declared, Francesco Finamore: None declared, Francesco Ferro: None declared, Marta Mosca Paid instructor for: GlaxoSmithKline, Lilly, UCB, Stefano Bombardieri: None declared, Silvia Rocchiccioli: None declared, Antonella Cecchettini: None declared
PB1736 IMPACT OF BCR FUSION TRANSCRIPTS ON OUTCOMES IN ACUTE PROMYELOCYTIC LEUKEMIA (APL)
Authors: V.R. Pydi, B.S. Chowdary, R.P. Yedla, S. Gundeti
Journal: HemaSphere (2019)

Background: Acute promyelocytic leukemia (APL) results from fusion of PML RARα gene and accounts for 10% of AML. The breakpoints on chromosome 17 are consistently located in the second intron of the RAR α gene, but on chromosome 15, there are different breakpoint cluster regions, namely bcr1, bcr2, and bcr3 located in intron 6, exon 6, and intron 3, respectively. About 70% of patients with APL have bcr‐1 or long (L)‐type transcript, 20% of patients with APL have bcr‐3 or short (S)‐type transcript, and 10% of patients have bcr‐2 or variant (V)‐type transcript Aims: The primary objective of this analysis was to study patient characteristics and outcomes in relation to bcr fusion transcripts of APL Methods: Data of all patients diagnosed as APL by PCR for PML RARα with known bcr transcripts were retrospectively analysed. Deaths within 72 hours of admission were excluded from the study. Statistical analysis was done using SPSS software, version 25. Overall survival was plotted using the Kaplan‐Meier method Results: A total of 54 patients were analysed. bcr 1, bcr 3, bcr 2 and bcr 2’3 transcripts were seen in 29(53.7%), 20(37%), 3(5.6%) and 2(3.7%) respectively. Ten out of 11 paediatric patients (91%) had bcr1 transcript at presentation. The baseline characteristics and chemotherapy regimens used are tabulated in Table 1. Differentiation syndrome during induction chemotherapy was seen in 6 (21%) and 3 (15%) patients in bcr1 and bcr 3 transcripts respectively. Five patients with bcr3 transcript, 2 patients with bcr1 transcript and one patient each in bcr2 and bcr2’3 transcripts succumbed during induction therapy. Sepsis (45%), followed by DIC (45%) were the most common causes of mortality. At a median follow up of 19 months, the overall survival rate was 93.1% and 74.3 % in bcr1 and bcr3 transcript groups respectively (p = 0.09). Summary/Conclusion: Most of the paediatric patients had bcr1 transcript at presentation. High risk at presentation was significantly higher in bcr3 group. Sepsis and DIC were the most common causes of induction mortality. Patients with bcr3 transcript had nonsignificant inferior survival compared to bcr1 image
Abstract 17619: Deep RNA-Sequencing Uncovers a Broad Species- And Cell-Specific lincRNA Repertoire That Modulates Human Macrophage Activation and Associates With Cardiometabolic Diseases
Authors: Hanrui Zhang, Chenyi Xue, Ying Wang, Xuan Zhang, Wenjun Li, Sara Nunez, Andrea S Foulkes, Jennie Lin, Christine C Hinkle, Wenli Yang, Edward E Morrisey, Daniel J Rader, Mingyao Li, Muredach P Reilly
Journal: Circulation (2017)

Introduction: Sustained and dysfunctional macrophage activation promotes inflammatory cardiometabolic disorders (CMDs), but the role of long non-coding RNAs in human macrophage activation and CMDs ...
Development of Capsular Fibrosis Beneath the Liver Surface in Humans and Mice
Authors: Steven Balog, Yuchang Li, Tomohiro Ogawa, Toshio Miki, Takeshi Saito, Samuel W. French, Kinji Asahina
Journal: Hepatology (2019)

Glisson's capsule is the connective tissue present in the portal triad as well as beneath the liver surface. Little is known about how Glisson's capsule changes its structure in capsular fibrosis (CF), which is characterized by fibrogenesis beneath the liver surface. In this study, we found that the human liver surface exhibits multilayered capsular fibroblasts and that the bile duct is present beneath the mesothelium, whereas capsular fibroblasts are scarce and no bile ducts are present beneath the mouse liver surface. Patients with cirrhosis caused by alcohol abuse or hepatitis C virus infection show development of massive CF. To examine the effect of alcohol on CF in mice, we first injected chlorhexidine gluconate (CG) intraperitoneally and then fed alcohol for 1 month. The CG injection induces CF consisting of myofibroblasts beneath the mesothelium. One month after CG injection, the fibrotic area returns to the normal structure. In contrast, additional alcohol feeding sustains the presence of myofibroblasts in CF. Cell lineage tracing revealed that mesothelial cells give rise to myofibroblasts in CF, but these myofibroblasts disappear 1 month after recovery with or without alcohol feeding. Capsular fibroblasts isolated from the mouse liver spontaneously differentiated into myofibroblasts and their differentiation was induced by transforming growth factor beta 1 (TGF‐β1) or acetaldehyde in culture. In alcohol‐fed mice, infiltrating CD11b + Ly‐6C Low/– monocytes had reduced mRNA expression of matrix metalloproteinase 13 and matrix metalloproteinase 9 and increased expression of tissue inhibitor of matrix metalloproteinase 1, Tgfb1 , and interleukin‐10 during resolution of CF. Conclusion: The present study revealed that the structure of Glisson's capsule is different between human and mouse livers and that alcohol impairs the resolution of CF by changing the phenotype of Ly‐6C Low/– monocytes.
Abstract 10895: Patient and Hospital Characteristics Associated With Ticagrelor Uptake in Acute MI: An Analysis of the NCDR ACTION Registry-GWTG
Authors: Benjamin A Rodwin, Di Lu, Antonio Giaimo, Joseph Lucas, Tracy Y Wang, Nihar R Desai
Journal: Circulation (2018)

Introduction: ACC/AHA guidelines support use of clopidogrel, prasugrel, and ticagrelor for secondary prevention among patients with acute myocardial infarction (AMI). Little is known about patient ...
China National Medical Products Administration approval summary: anlotinib for the treatment of advanced non-small cell lung cancer after two lines of chemotherapy
Authors: Ming Zhou, Xiaoyuan Chen, Hong Zhang, Lin Xia, Xin Tong, Limin Zou, Ruimin Hao, Jianhong Pan, Xiao Zhao, Dongmei Chen, Yuanyuan Song, Yueli Qi, Ling Tang, Zhifang Liu, Rong Gao, Yuankai Shi, Zhimin Yang
Journal: Cancer Communications (2019)

Abstract Background On May 8, 2018, the China National Medical Products Administration (NMPA) approved anlotinib, an orally administered anti‐angiogenesis inhibitor, for the treatment of patients with advanced non‐small cell lung cancer (NSCLC) who have progressed after treatment with two or more lines of prior systemic chemotherapy. Main body of the abstract China NMPA reviewed and inspected a regional double‐blinded, placebo‐controlled, Phase III trial comparing the overall survival (OS) of NSCLC patients between the anlotinib and placebo arms. A total of 437 patients were randomized (2:1) to receive either anlotinib ( n = 294) or placebo ( n = 143) once daily on a 2‐week on and 1‐week off schedule. Patients with epidermal growth factor receptor ( EGFR ) or activating anaplastic lymphoma kinase ( ALK ) genomic tumor aberrations should have disease progression on NMPA‐approved therapy. Anlotinib is the first NMPA‐approved drug for patients with advanced NSCLC who have progressed on at least two lines of prior systemic chemotherapies in China. The approval was based on a statistically and clinically significant improvement in median OS with anlotinib (9.46 months) compared with placebo [6.37 months; hazard ratio (HR]) = 0.70, 95% confidence interval (CI) = 0.55–0.89; two‐sided log‐rank P = 0.002]. The confirmed objective response rate (ORR) was 9.2% in the anlotinib arm and 0.7% in the placebo arm. The median duration of response (DoR) was 4.83 months, with a 95% CI of 3.31–6.97 months. The toxicity profile of anlotinib was consistent with that of known anti‐angiogenesis inhibitors. Common adverse drug reactions (ADRs) in anlotinib‐treated patients included hypertension (67.4%), hand–foot syndrome (43.9%), hemoptysis (14.0%), thyroid stimulating hormone (TSH) elevation (46.6%), and corrected QT interval (QTc) prolongation (26.2%). Short conclusion Anlotinib demonstrated a clinically significant OS prolongation as a novel therapeutic option for advanced or metastatic NSCLC following at least two lines of chemotherapy.
Addition of sirolimus to standard cyclosporine plus mycophenolate mofetil-based graft-versus-host disease prophylaxis for patients after unrelated non-myeloablative haemopoietic stem cell transplantation: a multicentre, randomised, phase 3 trial
Authors: Brenda M Sandmaier, Brian Kornblit, Barry E Storer, Gitte Olesen, Michael B Maris, Amelia A Langston, Jonathan A Gutman, Soeren L Petersen, Thomas R Chauncey, Wolfgang A Bethge, Michael A Pulsipher, Ann E Woolfrey, Marco Mielcarek, Paul J Martin, Fred R Appelbaum, Mary E D Flowers, David G Maloney, Rainer Storb
Journal: The Lancet Haematology (2019)