tbuckley/cabot-search huggingface dataset:
SAT0141 Changes of Bone Density and Microarchitecture in Rheumatoid Arthritis Patients with Early Disease: A One-Year Study with HR-PQCT: Table 1.
Authors: P.C. Wong, Y. Zhu, L. Qin, L.-S. Tam
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Periarticular and systemic osteoporosis is a major feature in patients with rheumatoid arthritis (RA). Bone loss in RA is considered to be a result of chronic inflammation, particularly at the early stage of the disease. High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) is an in vivo 3D imaging modality dedicated to peripheral skeleton imaging. Whether a better controlling of the disease inflammation could lead to a preservation of vBMD and microarchitecture is to be determined. <h3>Objectives</h3> This one-year cohort study in RA patients with early disease (onset &lt;2 years) aimed to compare changes of vBMD and bone microarchitecture indices at the distal radius and tibia between patients who achieved and those who did not achieve disease remission. <h3>Methods</h3> Forty-seven RA patients (age: 54.5±11.8 years) with disease onset &lt;2 years and with active disease (Disease Activity Score in 28 joints [DAS28] ≥3.2) were recruited for this one-year study. Disease remission at 12 months was assessed as Simplified Disease Activity Score ≤3.3. HR-pQCT imaging of the distal radius and tibia was performed at baseline and 12 months. <h3>Results</h3> At 12 months, 20 patients achieved disease remission and 27 patients remained with activity disease. There was no significant difference in baseline DAS28 score (4.93 vs. 4.92, p&gt;0.05) and age between the two groups. In patients who did not achieve disease remission, particularly at the distal radius, there were decreases in cortical and trabecular vBMD, cortical thickness and trabecular number, and increase in trabecular separation (Table 1). Increase in cortical porosity presented as the most prominent deterioration of bone microarchitecture (20%). Only changes in trabecular separation (2.87%) and cortical vBMD (-1.12%) achieve statistical significance. In patients who achieve disease remission, decrease in vBMD and deterioration in bone microarchitecture were in general to a lesser extent than their counterparts. In particular, there appeared to be a decrease in cortical porosity in these patients (-6.62%). However, there was no significant group-wise difference in changes of vBMD and microarchitectural indices (all p&gt;0.05). <h3>Conclusions</h3> There was a trend towards a preservation of vBMD and bone microarchitecture in RA patients who achieve disease remission. An early and better control of disease activity might reduce the future risk of osteoporosis in RA patients. <h3>Disclosure of Interest</h3> None declared
Identification of a fluorescent small-molecule enhancer for therapeutic autophagy in colorectal cancer by targeting mitochondrial protein translocase TIM44
Authors: Yinghui Huang, Jie Zhou, Shenglin Luo, Yang Wang, Jintao He, Peng Luo, Zelin Chen, Tao Liu, Xu Tan, Juanjuan Ou, Hongming Miao, Houjie Liang, Chunmeng Shi
Journal: Gut (2016)

Objective As the modulation of autophagic processes can be therapeutically beneficial to cancer treatment, the identification of novel autophagic enhancers is highly anticipated. However, current autophagy-inducing anticancer agents exert undesired side effects owing to their non-specific biodistribution in off-target tissues. This study aims to develop a multifunctional agent to integrate cancer targeting, imaging and therapy and to investigate its mechanism. Design A series of mitochondria-targeting near-infrared (NIR) fluorophores were synthesised, screened and identified for their autophagy-enhancing activity. The optical properties and biological effects were tested both in vitro and in vivo. The underlying mechanism was investigated using inhibitors, small interfering RNA (siRNA), RNA sequencing, mass spectrometry and human samples. Results We have screened and identified a new NIR autophagy-enhancer, IR-58, which exhibits significant tumour-selective killing effects. IR-58 preferentially accumulates in the mitochondria of colorectal cancer (CRC) cells and xenografts, a process that is glycolysis-dependent and organic anion transporter polypeptide-dependent. IR-58 kills tumour cells and induces apoptosis via inducing excessive autophagy, which is mediated through the reactive oxygen species (ROS)-Akt-mammalian target of rapamycin (mTOR) pathway. RNA sequencing, mass spectrometry and siRNA interference studies demonstrate that translocase of inner mitochondrial membrane 44 (TIM44)-superoxide dismutase 2 (SOD2) pathway inhibition is responsible for the excessive ROS, autophagy and apoptosis induced by IR-58. TIM44 expression correlates positively with CRC development and poor prognosis in patients. Conclusions A novel NIR small-molecule autophagy-enhancer, IR-58, with mitochondria-targeted imaging and therapy capabilities was developed for CRC treatment. Additionally, TIM44 was identified for the first time as a potential oncogene, which plays an important role in autophagy through the TIM44-SOD2-ROS-mTOR pathway.
SAT0408 Anti Tnf-α Therapy Provides Beneficial Effects on Choroidal Thickness Increase in Patients with Active Ankylosing Spondylitis: A Possible Mechanism of Infliximab Effectiveness in Suppressing Uveitis Attacks
Authors: M. Karkucak, A. Kalkısım, M. Kola, E. Capkın, A. Türk, A. Ayar
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Patients with ankylosing spondylitis (AS) have higher choroidal thickness values (CT) compared to controls. <h3>Objectives</h3> To quantitatively asses the profile of CT in patients with AS using optical coherence tomography (OCT), and to examine whether the posterior eye segment abnormalities in active AS patients were reversible by infliximab therapy <h3>Methods</h3> Thirty-one patients with AS receiving infliximab therapy and 24 healthy controls were enrolled. Patient9s clinical and demographic characteristics were recorded. Using OCT, we performed retinal imaging and choroidal <i>thickness measurements</i> in AS patients before and after 6 months of infliximab therapy, and in healthy controls who returned 6 months after the first visit. We compared patients before versus 6 months after infliximab therapy, as well as controls. <h3>Results</h3> Patients with AS had higher CT (mean± SD; 347.5±114.4 μm) compared to healthy controls (322.1±62.8 μm) (p=0.283), although this did not reach statistical significance. At 6 months after the first measurement, the mean CT was significantly decreased (after treatment with infliximab: 326.5±99.7μm vs. before: 347.5±114.4 μm, n=31, p=0.018) in AS group, but not in the control group (<i>p</i>=0.102). Retinal nerve fiber layer was significantly decreased at 6 months after treatment with infliximab in AS group (106.4±13.5 μm vs 105.0±13.0μm <i>p=0.008</i>). <h3>Conclusions</h3> This is the first study to evaluate the posterior eye segment in patients with AS using OCT. Our data indicate that CT abnormalities in active AS is reversible by therapy, and this CT decreasing effect of infliximab may be involved in its effective suppressing action of uveitis attacks in AS. <h3>References</h3> Balaskas K, Ballabeni P, Guex-Crosier Y. Retinal thickening in HLA-B27-associated acute anterior uveitis: evolution with time and association with severity of inflammatory activity. Invest Ophthalmol Vis Sci. 2012 14;53(10):6171–7. Kola M, Kalkışım A, Karkucak M, Turk A, Capkın E, Can I, Serdar OF, Mollamehmetoglu S, Ayar A. Evaluating of choroid thickness in Ankylosing spondylitis using optical coherence tomography. Ocular immunology and inflammation. 2014, 22(6):434–8. <h3>Disclosure of Interest</h3> None declared
Internal Tandem Duplications of FLT3 Induces Increased ROS Production, DNA Damage and Misrepair: Implications for Genomic Instability and Disease Resistance in Myeloid Malignancies.
Authors: Jinshui Fan, Annahita Sallmyr, Kyu-Te Kim, Kamal Datta, Paul Shapiro, Donald Small, Feyruz V. Rassool
Journal: Blood (2007)
Chemically engineered persistent luminescence nanoprobes for bioimaging
Authors: Thomas Lécuyer, Eliott Teston, Gonzalo Ramirez-Garcia, Thomas Maldiney, Bruno Viana, Johanne Seguin, Nathalie Mignet, Daniel Scherman, Cyrille Richard
Journal: Theranostics (2016)

Imaging nanoprobes are a group of nanosized agents developed for providing improved contrast for bioimaging. Among various imaging probes, optical sensors capable of following biological events or progresses at the cellular and molecular levels are actually actively developed for early detection, accurate diagnosis, and monitoring of the treatment of diseases. The optical activities of nanoprobes can be tuned on demand by chemists by engineering their composition, size and surface nature. This review will focus on researches devoted to the conception of nanoprobes with particular optical properties, called persistent luminescence, and their use as new powerful bioimaging agents in preclinical assays.
A Highly Durable RNAi Therapeutic Inhibitor of PCSK9
Authors: Kevin Fitzgerald, Suellen White, Anna Borodovsky, Brian R. Bettencourt, Andrew Strahs, Valerie Clausen, Peter Wijngaard, Jay D. Horton, Jorg Taubel, Ashley Brooks, Chamikara Fernando, Robert S. Kauffman, David Kallend, Akshay Vaishnaw, Amy Simon
Journal: New England Journal of Medicine (2016)

Inclisiran (ALN-PCSsc) is a long-acting RNA interference (RNAi) therapeutic agent that inhibits the synthesis of proprotein convertase subtilisin-kexin type 9 (PCSK9), a target for the lowering of low-density lipoprotein (LDL) cholesterol.In this phase 1 trial, we randomly assigned healthy volunteers with an LDL cholesterol level of at least 100 mg per deciliter in a 3:1 ratio to receive a subcutaneous injection of inclisiran or placebo in either a single-ascending-dose phase (at a dose of 25, 100, 300, 500, or 800 mg) or a multiple-dose phase (125 mg weekly for four doses, 250 mg every other week for two doses, or 300 or 500 mg monthly for two doses, with or without concurrent statin therapy); each dose cohort included four to eight participants. Safety, the side-effect profile, and pharmacodynamic measures (PCSK9 level, LDL cholesterol level, and exploratory lipid variables) were evaluated.The most common adverse events were cough, musculoskeletal pain, nasopharyngitis, headache, back pain, and diarrhea. All the adverse events were mild or moderate in severity. There were no serious adverse events or discontinuations due to adverse events. There was one grade 3 elevation in the γ-glutamyltransferase level, which was considered by the investigator to be related to statin therapy. In the single-dose phase, inclisiran doses of 300 mg or more reduced the PCSK9 level (up to a least-squares mean reduction of 74.5% from baseline to day 84), and doses of 100 mg or more reduced the LDL cholesterol level (up to a least-squares mean reduction of 50.6% from baseline). Reductions in the levels of PCSK9 and LDL cholesterol were maintained at day 180 for doses of 300 mg or more. All multiple-dose regimens reduced the levels of PCSK9 (up to a least-squares mean reduction of 83.8% from baseline to day 84) and LDL cholesterol (up to a least-squares mean reduction of 59.7% from baseline to day 84).In this phase 1 trial, no serious adverse events were observed with inclisiran. Doses of 300 mg or more (in single or multiple doses) significantly reduced levels of PCSK9 and LDL cholesterol for at least 6 months. (Funded by Alnylam Pharmaceuticals and the Medicines Company; ClinicalTrials.gov number, NCT02314442 .).
Unfavorable Cytogenetic Characteristics Do Not Adversely Impact Response Rates in Patients with Relapsed and/or Refractory Multiple Myeloma Treated with Single-Agent Carfilzomib on the 003 (A1) Study
Authors: Andrzej J Jakubowiak, David S. Siegel, Seema Singhal, Thomas Martin, Sagar Lonial, Vishal Kukreti, Nizar Bahlis, Asher Alban Chanan-Khan, Melissa Alsina, George Somlo, Francis K Buadi, Frederic J. Reu, Kevin W. Song, Lori Kunkel, Sandra M. Wear, Alvin F. Wong, Robert Z. Orlowski, A. Keith Stewart, Sundar Jagannath, Luhua Wang
Journal: Blood (2011)
Unrelated Alternative Donor Transplants for Severe Acquired Aplastic Anemia: A 12-Year Retrospective Study from the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC)
Authors: Raynier Devillier, Jean-Hugues Dalle, Laurence Clement, Noel Milpied, Patrice Chevallier, Yves Bertrand, Mauricette Michallet, Ibrahim Yakoub-Agha, Jean-Yves Cahn, Marc Bernard, Pascale Loiseau, Valerie Dubois, Gerard Socie, Regis Peffault de Latour
Journal: Blood (2014)
THU0179 Discontinuation of Nonsteroidal anti-Inflammatory Drugs in Rheumatoid Arthritis Patients with Low Disease Activity
Authors: D.J. Go, K. Shin, H.J. Baek, Y.M. Kang, S.W. Kang, S.H. Park, J.B. Jun, Y.J. Lee, Y.W. Song
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Although nonsteroidal anti-inflammatory drug (NSAIDs) is effective in relieving joint pain in rheumatoid arthritis (RA) patients, long-term use of NSAIDs can cause adverse effects on gastrointestinal or cardiovascular organs. When patients discontinue daily use of NSAIDs, there is often a dichotomous clinical response in patient-reported outcomes (PRO). <h3>Objectives</h3> We aimed to examine the clinical outcome especially joint pain, and its associated factors in RA patients with low disease activity (LDA) after discontinuing NSAIDs. <h3>Methods</h3> This study was a 16-week, multi-center prospective open-label trial conducted at eight rheumatology clinics in Korea. RA patients who achieved LDA (DAS28 &lt;3.2) who were on NSAIDs for more than 2 consecutive months, discontinued the NSAID. Acetaminophen (AAP) was used as the rescue medication. During the study period, changes of DAS28 and PRO including pain visual analogue scale (VAS) and Routine Assessment of Patient Index Data 3 (RAPID-3) score were assessed. NSAIDs were restarted when patient9s 1) pain was uncontrolled with AAP and 2) PRO were aggravated. The endpoint was to analyze the group of patients who continued to withdraw NSAIDs within the study period. Patients were further classified to have "sustained effectiveness" who met the following: 1) 16-week pain VAS ≤30 mm or increase less than 20% from baseline and 2) 16-week RAPID-3 score ≤6 or increase less than 20% from baseline. <h3>Results</h3> A total of 121 RA patients with LDA were enrolled in the study. Four patients were lost to follow-up. At the end of the study, 18 (15.3%) patients had restarted NSAIDs owing to uncontrolled pain. In general, there was a difference in pain VAS between baseline (median 15 mm (IQR 5–20)) and 16 weeks (median 17 mm (IQR 5–40)) (<i>p</i>=0.022). Changes of DAS28 and RAPID-3 were insignificant in patients taking on-demand AAP (n=99) (0 versus 16 weeks; DAS28, <i>p</i>=0.111; RAPID-3; <i>p</i>=0.339). Moreover, 60% of the total patients (73/117) ended up to show sustained effectiveness without restarting NSAIDs. By using a multivariate logistic regression model, we found out that joint swelling was the detrimental factor compromising sustained effectiveness (OR 0.312, 95% C.I. 0.125–0.777, <i>p</i>=0.012). <h3>Conclusions</h3> Discontinuation of NSAIDs can be attempted in RA patients with LDA, especially in those without swollen joints at the time point of its cessation. <h3>Disclosure of Interest</h3> None declared
Automated annotation and quantitative description of ultrasound videos of the fetal heart
Authors: Christopher P. Bridge, Christos Ioannou, J. Alison Noble
Journal: Medical Image Analysis (2016)

Interpretation of ultrasound videos of the fetal heart is crucial for the antenatal diagnosis of congenital heart disease (CHD). We believe that automated image analysis techniques could make an important contribution towards improving CHD detection rates. However, to our knowledge, no previous work has been done in this area. With this goal in mind, this paper presents a framework for tracking the key variables that describe the content of each frame of freehand 2D ultrasound scanning videos of the healthy fetal heart. This represents an important first step towards developing tools that can assist with CHD detection in abnormal cases. We argue that it is natural to approach this as a sequential Bayesian filtering problem, due to the strong prior model we have of the underlying anatomy, and the ambiguity of the appearance of structures in ultrasound images. We train classification and regression forests to predict the visibility, location and orientation of the fetal heart in the image, and the viewing plane label from each frame. We also develop a novel adaptation of regression forests for circular variables to deal with the prediction of cardiac phase. Using a particle-filtering-based method to combine predictions from multiple video frames, we demonstrate how to filter this information to give a temporally consistent output at real-time speeds. We present results on a challenging dataset gathered in a real-world clinical setting and compare to expert annotations, achieving similar levels of accuracy to the levels of inter- and intra-observer variation.
Genome-Wide Binding Studies of Acetyl-STAT3 Demonstrates a Novel Regulatory Pathway in Dendritic Cells
Authors: Yaping Sun, Matthew Iyer, Meng Zhao, Richard McEachin, Yi-Mi Wu, Xuhong Cao, Katherine Oravecz-Wilson, Cynthia Zajac, Nathan Mathewson, Julia Wu, Corinne Rossi, Tomomi Toubai, Zhaohui Qin, Arul Chinnaiyan, Pavan Reddy
Journal: Blood (2015)
The EUTOS Survival Score Is Preferable over the Sokal Score for Prognosis of Long-Term Survival of Patients with Chronic Myeloid Leukemia
Authors: Markus Pfirrmann, Joerg Hasford, Susanne Saussele, Anna Turkina, Witold Prejzner, Juan Luis Steegmann, Bengt Simonsson, Andrey Zaritskey, Adriana Colita, Daniela Zackova, Jeroen Janssen, Francisco Cervantes, Karel Indrak, Joelle Guilhot, Ruediger Hehlmann, Michele Baccarani
Journal: Blood (2015)
Reloadable multidrug capturing delivery system for targeted ischemic disease treatment
Authors: Jasmine P. J. Wu, Bill Cheng, Steve R. Roffler, David J. Lundy, Christopher Y. T. Yen, Peilin Chen, James J. Lai, Suzie H. Pun, Patrick S. Stayton, Patrick C. H. Hsieh
Journal: Science Translational Medicine (2016)

A reloadable drug capture system facilitates multidrug therapy for neovascularization after limb ischemia.
Breast Fibroadenoma With Increased Activity on 68Ga DOTATATE PET/CT
Authors: Georgios Z. Papadakis, Corina Millo, Samira M. Sadowski, Apostolos H. Karantanas, Ulas Bagci, Nicholas J. Patronas
Journal: Clinical Nuclear Medicine (2016)

Fibroadenoma is the most common benign breast tumor in women of reproductive age, carrying little to no risk of breast cancer development. We report on a case of a woman with history of neuroendocrine tumor who on follow-up imaging tests underwent whole-body PET/CT study using Ga DOTATATE. The scan showed increased focal activity in the right breast, which was biopsied revealing a fibroadenoma. The presented data suggests cell surface overexpression of somatostatin receptors by this benign breast tumor. Moreover, this finding emphasizes the need for cautious interpretation of Ga DOTATATE-avid breast lesions that could mimic malignancy in neuroendocrine tumor patients.
Earlier Antenatal Diagnosis of Hemoglobinopathies By Coelocentesis
Authors: Antonino Giambona, Gianfranca Damiani, Filippo Leto, Cristina Yakil, Cristina Passarello, Valentina Cigna, Giovanna Schillaci, Massimiliano Sacco, Rosario Di Maggio, Angela Vitrano, Aurelio Maggio
Journal: Blood (2015)
Pattern of head and neck cancer in a tertiary institution in Lagos, Nigeria.
Authors: Anthonia Chima Sowunmi, Kingsley Kayode Ketiku, Popoola Abiodun Olaniyi, Adewumi Olabimpe Alabi, Omolara A. Fatiregun, Nkiru Asoegwu, Temitope Abiodun Olatunji, Kehinde Adefolarin Blackson
Journal: Journal of Clinical Oncology (2015)

e17052 Background: The real burden of head and neck cancer n Nigeria with a population of over 167million is a major health problem coupled with the limited infrastructure and equipments needed for its treatment in the developing countries. Incidence in Nigeria has not been accurate, however, studies done are hospital based. The aim is to study the current pattern of head and neck cancer in Lagos. Methods: A retrospective study of patients with histologically confirmed head and neck cancer seen in the oncology/radiotherapy department of Lagos University Teaching Hospital in Lagos ,Nigeria between January 2005 – December 2011. Social factors and clinical factors such as age, gender, histology, site of disease, stage, treatment modalities of patients were retrieved from the case notes Results: A total of 162cases of histologically diagnosed head and neck cancer were retrieved resulting in about 23 cases annually and a prevalence of 6.74%. the age of patients ranged from 3 – 99years , with a mean age of 49.50±19.73years, the peak age range was 4th – 5th decade(40.2%) was mostly reported for cancer occurrence. There were 102(63%) male and 60(37%) female with a M:F of 1.7:1. The commonest histological type was squamous cell carcinoma, accounting for 100(75.2%) out of the 133 cases of carcinoma reported. The commonest site of distribution was nasopharynx 22(13.6%). Out of the 67 cases with recorded stage of disease, 54(80.6%) were stages III &IV. Treatment modalities revealed that 53(32.7%) had radiotherapy alone was the commonest treatment administered. Conclusions: There is a decrease in annual incidence with nasopharynx remaining the commonest site with a study done previously in this location. Increased national awareness programs emphasizing the preventable risk factors associated with this cancer and change in life style will decrease the morbidity and mortality associated with late presentation despite the limited treatment equipments.
AB0561 Heart Involvement in Patients with Eosinophilic Granulomatosis with Polyangiitis
Authors: N. Nikitina, O. Aleksandrova, I. Nam, N. Rodionova, A. Rebrov
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Cardiac involvement is factor of poor prognosis in eosinophilic granulomatosis with polyangiitis (EGPA). Due to current data, heart lesions in EGPA are associated with higher peripheral eosinophilia. However, data about cardiac manifestations of EGPA are limited. The aim of the study was to evaluate the frequency of occurrence of heart involvement in patients with EGPA, and to study interrelation of heart lesion and peripheral eosinophilia and other signs of the disease. <h3>Objectives</h3> Were analyzed 19 case histories of patients with EGPA (13 women and 6 men, mean age ± SD – 49.8±14.8 years, mean disease duration – 4.6±3.76 years). The patients were treated in Saratov regional hospital, rheumatology department. <h3>Methods</h3> Were used clinical tests and echocardiography. <h3>Results</h3> 7 (36.8%) patients had features of heart damage. In 2 patients were found clinical signs of myocarditis, confirmed with echocardiography (ejection fraction 48 and 50%, respectively). In 1 patient was found fibrosis of atrioventricular valves, in 3 patients – signs of valvular insufficiency, in 1 – was diagnosed coronariitis. Eosinophils number was increased in 11 patients: in 4 from 7 patients with cardiac involvement and in 8 from 11 without heart lesion. The highest number of eosinophils was found in 2 patients with miocarditis (40 and 43%, respectively). Improvement in miocarditis and ejection fraction under the treatment was associated with decrease of eosinophils count. In other patients during the treatment (12–24 month of follow-up) eosinophils count was normalized. There were no new features of cardiac involvement under the treatment. <h3>Conclusions</h3> Patients with EGPA frequently have cardiac involvement. Miocarditis is associated with high eosinophils9 count. Heart involvement is reversible and has no trend to progression under the treatment. <h3>Disclosure of Interest</h3> None declared