tbuckley/cabot-search huggingface dataset:
Abstract 12827: Alterations in Flow Patterns and Wall Shear Stress in Pulmonary Artery Visualized With Phase-resolved 3D Cine Phase Contrast MRI (4D-Flow) in Patients With Systemic Sclerosis
Authors: Kenichiro Suwa, Tomoaki Sakakibara, Takeji Saitoh, Yutaro Kaneko, Makoto Sano, Masao Saotome, Tsuyoshi Urushida, Hideki Katoh, Hiroshi Satoh, Yasuo Takehara, Harumi Sakahara, Hideharu Hayashi
Journal: Circulation (2015)

Background: The pulmonary circulation is impaired in patients with systemic sclerosis (SSc), and the analysis of pulmonary arterial (PA) blood flow has a great clinical significance. Using 4D-Flow, we studied the changes in PA blood flow velocity vectors and wall shear stress (WSS) in SSc patients. Methods: Twenty one SSc patients (M/F: 1/20, 56±15 years) including 2 PA hypertension, and 7 control subjects underwent 4D-Flow. We set planes traversing the main and first branches of PA, and the velocity vectors were post-processed to delineate streamline images. WSS images were obtained at the surface of PA. The plane-averaged flow velocity at the main PA, surface-averaged WSS, and oscillatory shear index (OSI), the %WSS acting in other directions from the mean WSS vector during a cardiac cycle, were compared. Results: (1) The PA flow showed laminar flow pattern at the early systolic phase in all patients and subjects, but diffuse helical flow in 11 SSc patients (right upper), focal helical flow in 6 SSc patients and 2 control subjects at the late systolic to early diastolic phase. The other 4 SSc patients and 5 control subjects had continuous laminal flow (left upper). (2) The peak systolic PA flow velocity did not differ between them, whereas the diastolic flow velocity was significantly greater in SSc patients (minimum velocity; 26±24 mm/sec vs. -26±52 mm/sec, p&lt;0.01). (3) WSS at the peak systolic flow velocity was significantly lower and spatially heterogeneous in SSc patients (lower figs; 1.1±0.2 Pa vs. 1.4±0.4 Pa, p&lt;0.01). Both WSS at the diastolic phase and OSI were significantly greater in SSc patients (minimum WSS; 0.28±0.07 Pa vs. 0.19±0.04 Pa, p&lt;0.01, OSI; 0.14±0.03% vs. 0.09±0.02%, p&lt;0.05). Conclusions: The 4D-Flow disclosed the different PA flow patterns between SSc patients and control subjects. In SSc patients, WSS at the PA was generally decreased and varied spatially and temporally. 4D-Flow has a potential to detect the subclinical changes of PA flow dynamics in SSc.
AB1000 THE SURVIVAL OF METHOTREXATE IN JUVENILE IDIOPATHIC ARTHRITISCHILDREN AFTER DURING FIRST BIOLOGIC TREATMENT
Authors: Rinat Raupov, Lubov Sorokina, Yuri Korin, Ilya Avrusin, Elizaveta Orlova, Ekaterina Gaidar, Margarita Dubko, Vera Masalova, Tatiana Likhacheva, Ludmila Snegireva, Eugenia Isupova, Tatiana Kornishina, Olga Kalashnikova, Mikhail Kostik
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Methotrexate (MTX) is a gold standard for treatment of juvenile idiopathic arthritis (JIA) patients. The main adverse events (AE) related to the MTX are intolerance, increased rate of infections, elevation of the liver enzymes, hematological abnormalities and stomatitis, which required to stop the MTX therapy [1]. In children without remission who tolerated MTX often the second-line treatment is the biologics, which may use alone or in the combination with MTX. <h3>Objectives</h3> The aim of our study was to evaluate the main reasons of MTX discontinuation in JIA children who started first biologic. <h3>Methods</h3> In the study were included 173 non-systemic JIA patients, whom biologic therapy was prescribed firstly to previous MTX treatment. We evaluate the main reasons of MTX discontinuation after the starting of the biologic treatment, duration of MTX treatment (all and after biologic start), achievement the remission, according C. Wallace criteria and time to remission, flare of JIA. We compared two groups: i) patients with biologics with ongoing methotrexate and ii) patients with biologics alone, whom MTX was discontinued or not prescribed. <h3>Results</h3> During the trial MTX discontinued 40 (23.1%) patients: due to intolerance (n=11), other adverse events (AE) (n=10), except intolerance (mainly, frequent infection and transaminitis) and remission of JIA (n=19). Patients with onset age of JIA &lt;4.4 years were in the risk of developing MTX intolerance (LogRank test, p=0.000001), but the younger patients usually developed other AE. Compare of the three subgroups of patients, who discontinued MTX we have not yet found any differences, except the onset age and frequency of remission, which was higher in patients who discontinued MTX due to other AE than due to intolerance. <h3>Conclusion</h3> The main factor, associated with MTX discontinuation in JIA patients, who received first biologic was the disease onset age. Eldest age was related to higher risk of developing the MTX intolerance. <h3>References</h3> [1] van Dijkhuizen EH, Pouw JN, Scheuern A, Hügle B, Hardt S, Ganser G, Kümmerle-Deschner JB, Horneff G, Holzinger D, Bulatović Ćalasan M, Wulffraat NM. Methotrexate intolerance in oral and subcutaneous administration in patients with juvenile idiopathic arthritis: a cross-sectional, observational study. Clin Exp Rheumatol. 2016;34(1):148-54. <h3>Disclosure of Interests</h3> None declared
Abstract 145: Long Term Follow-up Of Children With Kawasaki Disease (KD) Treated With Infliximab (IFX) - Our Experience At Chandigarh, North India
Authors: Dhrubajyoti Sharma, Anju Gupta, Manojkumar Rohit, Deepti Suri, Amit Rawat, Surjit Singh
Journal: Circulation (2015)

Background: Tuberculosis (TB) is endemic in India. Flare-up of TB is a concern in children treated with IFX. Objective: To report long-term follow-up of children with KD treated with IFX. Patients and methods: Study design: Review of records of 17 children with KD who had received IFX. Median age was 1.5 years (range 2 months to 6 years) Study setting: Pediatric Rheumatology Clinic, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, North India. Study duration: January 2007 to July 2014. Patient group: Patients with diagnosis of KD and given IFX were included and analyzed. 15 of these patients had received intravenous immunoglobulin (2g/kg) as first line therapy. Dose of IFX was 5-7 mg/kg given intravenously. Screening tests for TB (chest X-ray, tuberculin test) were not carried out prior to IFX infusion. Duration of follow-up:6 -12 months in 6 patients;13-30 months in 5 patients;45-65 months in 5 patients and 80 months in 1 patient (mean follow-up 30.6 ± 24.4 months). Results: None of the patients had any significant adverse reactions during infusion of IFX. On follow-up none of these patients has developed TB or any other significant infection. Twelve (12)/17 patients showed coronary artery abnormalities (CAAs) (table). Post IFX, 66% (8 of 12) patients with KD showed improvement in CAAs on follow-up. Conclusion: In our experience use of IFX was not associated with flare-up of any significant bacterial infection (including TB) during follow-up. 8/12 patients with CAAs showed resolution.
Brain and cancer: The protective role of erythropoietin
Authors: Michele Buemi, Chiara Caccamo, Lorena Nostro, Emanuela Cavallaro, Fulvio Floccari, Giovanni Grasso
Journal: Medicinal Research Reviews (2004)

Abstract Erythropoietin (Epo) is a pleiotropic agent, that is to say, it can act on several cell types in different ways. An independent system Epo/Epo receptor (EpoR) was detected in brain, leading to the hypothesis that this hormone could be involved in cerebral functions. Epo/EpoR expression changes during ontogenesis, thus indicating the importance of this system in neurodevelopment. Moreover, the hypoxia‐induced production of Epo in the adult brain suggests that it could exert a neurotrophic and neuroprotective effect in case of brain injury. Epo could also influence neurotransmission, inducing neurotransmitters (NT) release. Epo therapy in anemic cancer patients is still a controversial issue, because of its possible action as a growth and an angiogenic factor. In our speculative hypothesis Epo could be involved in a “two steps process” that, after a neovascularization phase, leads to its down regulation. Moreover, Epo‐activated signaling pathways could be modulated as possible targets to interfere in neoplastic cells cycle. In conclusion, treatment with rHuEpo could change therapeutical perspectives in different pathological conditions, such as central nervous system (CNS) diseases, but further studies are needed to clarify its physiopathological activities in different clinical fields. © 2004 Wiley Periodicals, Inc.
PF716 CLINICAL IMPACT OF PROGNOSTIC NUTRITIONAL INDEX IN DIFFUSE LARGE B CELL LYMPHOMA
Authors: S.‐I. Go, G.‐W. Lee
Journal: HemaSphere (2019)

Please indicate where the abstract has been published before: Annals of Hematology Background: Cachexia is an indicator of tumor progression in patients with malignancy. Cachectic patients exhibit intolerance and a reduced response to antitumor therapy, and have an unfavorable prognosis. An international consensus proposed diagnostic criteria for cancer cachexia including weight loss, low body mass index (BMI), and/or presence of sarcopenia. Other potential biomarkers (e.g., albumin, C‐reactive protein, pro‐inflammatory cytokines, and microRNAs) and scoring systems (e.g., cachexia score [CASCO], Glasgow prognostic score [GPS], prognostic nutritional index [PNI]) have also been studied to diagnose cancer cachexia and assess its severity. Aims: In this study, we assessed the associations among PNI, other clinical outcomes, and survival in patients with DLBCL. Then we sought valid cachexia markers with prognostic significance and designed a novel model to improve the prognostic ability of well‐known clinical indices for patients with DLBCL. Methods: A total of 228 DLBCL patients treated with first‐line R‐CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) were retrospectively reviewed. PNI was calculated as 10 × serum levels of albumin (g/dL) + 0.005 × absolute lymphocyte count (/mm 3 ). Patients were categorized into low‐ and high‐PNI groups based on a cut‐off value of 40. The nomogram for predicting overall survival (OS) was constructed using a Cox regression model. PNI was positively correlated with skeletal muscle index, body mass index, and serum levels of albumin. Results: The low‐PNI group had a lower complete response rate (60.3% vs. 87.6%), increased treatment‐related toxicity, and more frequent treatment discontinuation (43.5% vs. 8.8%) than the high‐PNI group. The median OS was shorter in the low‐PNI group than the high‐PNI group (15.6 months vs. not reached; p &lt; 0.001, Figure.1). Multivariate Cox regression analyses showed that PNI, sarcopenia, and the international prognostic index (IPI) were independent prognostic factors for OS. The nomogram developed using this regression model showed excellent discriminatory ability for predicting OS (c‐index, 0.80) compared to the IPI alone (c‐index, 0.75). Summary/Conclusion: This study supports the results of a previous study [29], whereby low PNI is an independent poor prognostic factor in patients with DLBCL treated with first‐line R‐CHOP immunochemotherapy. In addition, we newly found that treatment‐related toxicity and early discontinuation of treatment occurred more frequently in DLBCL patients with low PNI. We anticipate that the new prognostic nomogram developed using PNI, SMI, and IPI may help to realize individualized therapy that considers both the disease characteristics and the patient's tolerance to treatment in patients with DLBCL. This will be validated externally in a future study. image
AB0843 HYPOVITAMINOSIS D IN A MARFAN POPULATION
Authors: Daniela Melchiorre, Elisa Pratelli, Renato Colombai, Marco Matucci-Cerinic, Guglielmina Pepe
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Marfan syndrome is an autosomal dominant disorder of connective tissue caused by mutations in FBN1 gene on the long arm of chromosome 15. Information is often lacking regarding an increased risk of fractures and its management and prevention in patients with Marfan syndrome. In these patients reduced bone mineral density was rarely reported. A pivotal role in bone mineralization is played by Vitamin D. <h3>Objectives</h3> This study evaluates whether the reduction of the values of Vitamin D is present in Marfan patients. <h3>Methods</h3> 60 patients (pts) (28 M/32 F; age 15-75 mean age 46,2) with Marfan syndrome were studied. The patients were followed from the clinical and research regional Marfan Center in Florence, Italy. All pts met new Ghent criteria that identified ectopia lentis, thoracic aorta dilatation with Z score = or &gt; 2 and a large group of systemic clinical features represented by cardiovascular, musculoskeletal, central nervous system (dural ectasia) pulmonary, cutaneous and ocular clinical manifestations (systemic features) reaching a score = or &gt; 7 as major clinical criterion. Familiarity and the detection of a gene mutation (in MFS FBN1 gene displays a mutation in about 90% of patients) are also considered criteria necessary for Marfan diagnosis. <h3>Results</h3> 11/60 pts (18,3%) (5M/6F age 15-75 mean age 44,9) showed reduced values of Vitamin D. 6/11 pts (45,4%) (3M/3F age 15-56, mean age 34,1) showed very poor Vitamin D values (range 8.7 ng/ml – 13,17 ng/ml). <h3>Conclusion</h3> Our results suggests that Vitamin D may play an important role in bone metabolism in Marfan patients. These results need confirmation since further data are missing in literature. <h3>References</h3> [1] Trifirò G, Marelli S, Viecca M, Mora S, Pini A. Areal bone mineral density in children and adolescents with Marfan syndrome: evidence of an evolving problem. [2] Bone. 2015Apr;73:176-80. doi: 10.1016/j.bone.2014.12.006. Epub 2014 Dec 13. <h3>Disclosure of Interests</h3> Daniela Melchiorre: None declared, Elisa Pratelli: None declared, Renato Colombai: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Pfizer, BMS, Chemomab, Sanipedia, Speakers bureau: Actelion, BMS; MSD, Janssen, Guglielmina Pepe: None declared
PF795 EXPLORING THE REAL‐LIFE CLINICAL VALUE OF LOW DOSE DIRECT ANTICOAGULANTS FOR SECONDARY PREVENTION OF THROMBOEMBOLISM
Authors: S. Saul, G. McIlroy, N. Smith, D. Perrin, S. Fair, C. Kartsios
Journal: HemaSphere (2019)

Background: Anticoagulation is the mainstay of acute venous thromboembolism (VTE) therapy. Until recently Vitamin‐K antagonists (VKAs) were the standard of care for extended treatment of VTE. In the last decade, direct oral anticoagulants (DOACs) have been studied and approved for use in treatment and secondary prevention of VTE. The apixaban AMPLIFY‐EXTEND clinical trial and the rivaroxaban EINSTEIN CHOICE study, have offered evidence that low dose anticoagulation up to 12 months following completion of standard VTE treatment, can be equally effective to standard dose apixaban/rivaroxaban for secondary prevention of thromboembolism. To date there is no real‐life study recording the outcomes of patients on low dose DOACs in this setting. Aims: In this audit, we sought to identify patients on long term low dose apixaban/rivaroxaban for secondary prevention of VTE and record their outcomes. Methods: Between January 2015 and September 2018, 4,625 patients were initiated to DOACs in our clinics. Amongst them 394 patients were put on either apixaban 2.5 mg bd (N = 352) or rivaroxaban 10 mg od (N = 42). Their median age was 65(16–98) years. The index event to offer long term anticoagulation was unprovoked VTE in 271 patients while 123 had suffered a provoked VTE with permanent risk factors. Cancer‐associated thrombosis was recorded in 42 patients, 69 individuals had documented thrombophilia and/or family history of thrombosis. Recurrent VTE was recorded in 41 patients. The median time from thrombosis to low‐dose anticoagulation switch was 7.26(3–280) months. The median follow‐up time on low dose anticoagulation was 15(3–45) months. Results: Major bleeding occurred in 3/394 patients (0.76%), all 3 patients were on low dose apixaban. Major plus clinically relevant non‐major bleeding was recorded in 30 patients (7.6%). Recurrent VTE occurred in 13/352 patients (3.69%) in the apixaban group and 1/42 patients (2.3%) in the rivaroxaban group (p = NS). No statistical differences in bleeding rate and VTE recurrence were identified between the total patient population, the cancer related thrombosis and the thrombophilia/family history of VTE subgroup respectively (table). Summary/Conclusion: Our study although small, is the first to record the clinical experience of using long term low dose DOACs to prevent VTE recurrence in real life. Our results confirm that low dose DOACs are very safe with major bleeding rate oof &lt;1% in 15 months. We did however find a higher incidence of recurrent VTE (3.55%) compared to the AMPLIFY‐EXTEND (1.7%) and the EINSTEIN CHOICE (1.2%) trials. image
Genetic Tracing Identifies Early Segregation of the Cardiomyocyte and Nonmyocyte Lineages
Authors: Yan Li, Zan Lv, Lingjuan He, Xiuzhen Huang, Shaohua Zhang, Huan Zhao, Wenjuan Pu, Yi Li, Wei Yu, Libo Zhang, Xiuxiu Liu, Kuo Liu, Juan Tang, Xueying Tian, Qing-Dong Wang, Kathy O. Lui, Bin Zhou
Journal: Circulation Research (2019)

The developing heart is composed of cardiomyocytes and noncardiomyocytes since the early stage. It is generally believed that noncardiomyocytes including the cardiac progenitors contribute to new cardiomyocytes of the looping heart. However, it remains unclear what the cellular dynamics of nonmyocyte to cardiomyocyte conversion are and when the lineage segregation occurs during development. It also remains unknown whether nonmyocyte to cardiomyocyte conversion contributes to neonatal heart regeneration.We quantify the lineage conversion of noncardiomyocytes to cardiomyocytes in the embryonic and neonatal hearts and determine when the 2 cell lineages segregate during heart development. Moreover, we directly test if nonmyocyte to cardiomyocyte conversion contributes to neonatal heart regeneration.We generated a dual genetic lineage tracing strategy in which cardiomyocytes and noncardiomyocytes of the developing heart could be simultaneously labeled by 2 orthogonal recombination systems. Genetic fate mapping showed that nonmyocyte to cardiomyocyte conversion peaks at E8.0 (embryonic day) to E8.5 and gradually declines at E9.5 and E10.5. Noncardiomyocytes do not generate any cardiomyocyte at and beyond E11.5 to E12.5. In the neonatal heart, noncardiomyocytes also do not contribute to any new cardiomyocyte in homeostasis or after injury.Noncardiomyocytes contribute to new cardiomyocytes of the developing heart at early embryonic stage before E11.5. The noncardiomyocyte and cardiomyocyte lineage segregation occurs between E10.5 and E11.5, which is maintained afterward even during neonatal heart regeneration.
WebMeV: A Cloud Platform for Analyzing and Visualizing Cancer Genomic Data
Authors: Yaoyu E. Wang, Lev Kutnetsov, Antony Partensky, Jalil Farid, John Quackenbush
Journal: Cancer Research (2017)

Abstract Although large, complex genomic datasets are increasingly easy to generate, and the number of publicly available datasets in cancer and other diseases is rapidly growing, the lack of intuitive, easy-to-use analysis tools has remained a barrier to the effective use of such data. WebMeV (http://mev.tm4.org) is an open-source, web-based tool that gives users access to sophisticated tools for analysis of RNA-Seq and other data in an interface designed to democratize data access. WebMeV combines cloud-based technologies with a simple user interface to allow users to access large public datasets, such as that from The Cancer Genome Atlas or to upload their own. The interface allows users to visualize data and to apply advanced data mining analysis methods to explore the data and draw biologically meaningful conclusions. We provide an overview of WebMeV and demonstrate two simple use cases that illustrate the value of putting data analysis in the hands of those looking to explore the underlying biology of the systems being studied. Cancer Res; 77(21); e11–14. ©2017 AACR.
IL-10-Dependent Crosstalk between Murine Marginal Zone B Cells, Macrophages, and CD8α+ Dendritic Cells Promotes Listeria monocytogenes Infection
Authors: Dong Liu, Xiangyun Yin, Sam J. Olyha, Manuela Sales L. Nascimento, Pei Chen, Theresa White, Uthaman Gowthaman, Tingting Zhang, Jake A. Gertie, Biyan Zhang, Lan Xu, Marina Yurieva, Lesley Devine, Adam Williams, Stephanie C. Eisenbarth
Journal: Immunity (2019)
AB0873 ENDOTHELIAL DYSFUNCTIONIN PATIENTS WITH GOUT. RELATIONSHIP BETWEEN CARDIOVASCULAR RISK FACTORS
Authors: Ekaterina Ilinykh, Maxim Eliseev, Alexander Volkov
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Patients with gout have a high risk of developing cardiovascular disease based on atherosclerosis. An early marker, and at the same time a risk factor of cardiovascular disease, is a violation of the vasoregulating endothelial activity. <h3>Objectives</h3> To identify the relationship between cardiovascular risk factors and endothelial dysfunction (ED) in patients with gout. <h3>Methods</h3> The study included 80 pts with gout. The criteria for inclusion were 1.Male 2.Age &gt;55 years 3.Interictal period of arthritis 4.Absence of clinical signs of coronary artery disease 5.Absence of drug therapy. Vasoregulating endothelial activity was evaluated in all pts, 52 of them determined the carotid intima-media thickness (C-IMT). Flow-mediated (endothelium-dependent) dilatations (FMD), nitroglycerin-induced (endothelium - independent) dilatation (EID) were assessed by highresolution ultrasonography (D. Celermajer). A non-invasive ultrasound technique was used to measure C-IMT. All patients were diagnosed with serum total cholesterol (CHOL), subtypes (LDL-C, HDL-C), glucose (GLU), uric acid (SUA), hsCRP. Cardiovascular risk (CVR) was calculated. Statistical analysis was conducted using the applied programs package of descriptive statistics STATISTICA 12.0 (StatSoft.Inc.,USA). <h3>Results</h3> It was found that 41 (51.25%) pts had FMD less than 8%. A correlation was found between FMD and CVR (r= -0.28, p &lt;0.05), age (r= -0.37, p&lt;0.001), Body mass index (BMI) (r= -0.23, p&lt;0.05). The links between FMD and LDL, GLU, SUA and with parameters reflecting the severity of gout were not revealed (p&gt;0.05). C-IMT in pts was 0.7 (0.6-0.8) mm. 7 (14,4%) pts had &gt; 1.0 mm. A direct correlation was found between the C-IMT and the FMD (p &lt;0.01), CVR (p &lt;0.001), age (p &lt;0.001), duration of gout (p &lt;0.001), the number of joints affected for all time (p &lt;0.005) and the frequency of arthritis in the last year (p &lt;0.05). Correlation between C-IMT and LDL, GLU, SUA, hsCRB was not revealed (p&gt;0.05). <h3>Conclusion</h3> The ED, reflecting the risk of atherosclerosis, was found in 51.3% of patients with gout under the age of 55 years without clinical signs of coronary artery disease. The ED is associated with an increase in the CVR. C-IMT correlates with an increase in CVR and with parameters reflecting the severity of gout. <h3>References</h3> [1] Celermajer D.S, Sorensen K.E., Gooch V.M. et al. Non-invasive detection of endothelial dysfunction in children and adults at risk atherosclerosis//Lancet.- 1992. - Vol.340. - P.1111-1115. [2] Corretti M.C., Anderson T.J., Benjamin E.J. et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of brachial artery//Jam. Coll. Cardiol. – 2002. - Vol.39. – P.257-265. <h3>Disclosure of Interests</h3> None declared