tbuckley/cabot-search huggingface dataset:
Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study
Authors: Frederic Castinetti, Steven G Waguespack, Andreas Machens, Shinya Uchino, Kornelia Hasse-Lazar, Gabriella Sanso, Tobias Else, Sarka Dvorakova, Xiao Ping Qi, Rossella Elisei, Ana Luisa Maia, John Glod, Delmar Muniz Lourenço, Nuria Valdes, Jes Mathiesen, Nelson Wohllk, Tushar R Bandgar, Delphine Drui, Marta Korbonits, Maralyn R Druce, Caroline Brain, Tom Kurzawinski, Atila Patocs, Maria Joao Bugalho, Andre Lacroix, Philippe Caron, Patricia Fainstein-Day, Francoise Borson Chazot, Marc Klein, Thera P Links, Claudio Letizia, Laura Fugazzola, Olivier Chabre, Letizia Canu, Regis Cohen, Antoine Tabarin, Anita Spehar Uroic, Dominique Maiter, Sandrine Laboureau, Caterina Mian, Mariola Peczkowska, Frederic Sebag, Thierry Brue, Delphine Mirebeau-Prunier, Laurence Leclerc, Birke Bausch, Amandine Berdelou, Akihiro Sukurai, Petr Vlcek, Jolanta Krajewska, Marta Barontini, Carla Vaz Ferreira Vargas, Laura Valerio, Lucieli Ceolin, Srivandana Akshintala, Ana Hoff, Christian Godballe, Barbara Jarzab, Camilo Jimenez, Charis Eng, Tsuneo Imai, Martin Schlumberger, Elizabeth Grubbs, Henning Dralle, Hartmut P Neumann, Eric Baudin
Journal: The Lancet Diabetes & Endocrinology (2019)
Abstract 18953: Prevalence of and Risk Factors for Radial Artery Complications After Transradial Cardiac Catheterization
Authors: Johannes Ruhnau, Stephen Schröder
Journal: Circulation (2013)

Background: In recent years, radial access for cardiac catheterization gains popularity. One of the most common complications is radial artery occlusion (RAO). There are various numbers for the prevalence of RAO in literature, ranging from 5 to 30% when using a 6F sheath. Our study was designed to investigate the prevalence of radial artery (RA) complications (RAO, false aneurysm, arteriovenous fistula) in a single center population using a 6F sheath. Methods: 415 patients* (pts) were examined clinically and with duplex sonography 4 - 68 weeks after cardiac catheterization (60.7% (n=254) male, median age 68 y (33 - 88). In n=103 pts (24.6%) an intervention had been performed immediately after the diagnostics. Results: Patient characteristics are summarized in table 1. RAO was found in 15/418 cases (3.6%, n = 10 female, n = 5 male). Of those 10 patients, 3 showed (transient) symptoms (dysaesthesia, feeling of heaviness of the hand), cases of critical ischaemia were not found. No false aneurysm was found, one pt showed an arteriovenous fistula in the proximal RA. One patient showed significant stenosis of the middle portion of the brachial artery in addition to RAO, another one showed a mild stenosis of the RA. Women showed a significantly higher rate of RAO (n = 10, 66.7% in the RAO group vs. n = 154, 40.3% in the comparison group, p = 0.03). Other risk factors seem to be diabetes (n = 6, 40% vs. n = 106, 26%) and renal insufficiency (n = 3, 20% vs. n = 43, 11%), although the risk was not significantly increased. Interestingly, a coronary intervention does not seem to increase the risk of RAO (n = 2, 13% vs. n = 101, 26%). Hypertension, dyslipidemia, present or past smoking, body height, age, and BMI did not have significant influence. Conclusion: Vascular complications, especially RAO, after radial access for cardiac catheterization are quite rare and remain usually asymptomatic. Women are at higher risk. Diabetic pts and pts with impaired renal function seem to be at slightly higher risk.
Long Term Results of a Randomized Phase 2 Dose-Response Study of Guadecitabine, a Novel Subcutaneous (SC) Hypomethylating Agent (HMA), in 102 Patients with Intermediate or High Risk Myelodysplastic Syndromes (MDS) or Chronic Myelomonocytic Leukemia (CMML)
Authors: Guillermo Garcia-Manero, Ellen K. Ritchie, Katherine J. Walsh, Michael R. Savona, Hagop M. Kantarjian, Patricia L. Kropf, Casey L. O'Connell, Raoul Tibes, Naval G. Daver, Elias J. Jabbour, Scott D. Lunin, Todd L. Rosenblat, Karen W.L. Yee, Wendy Stock, Elizabeth A. Griffiths, Joseph Mace, Nikolai A. Podoltsev, Jesus G. Berdeja, Jean-Pierre Issa, Sue Naim, Yong Hao, Mohammad Azab, Gail J. Roboz
Journal: Blood (2018)
FRI0045 Evaluation of serum protein levels at baseline as predictors of response to methotrexate in patients with early rheumatoid arthritis: results from swefot trial population
Authors: K. Hambardzumyan, C. Hamsten, H. Idborg, L. Lourido, S. Saevarsdottir, P. Nilsson, R.F. van Vollenhoven, P.-J. Jakobsson
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Methotrexate (MTX) is a standard first-line therapy option for patients with early rheumatoid arthritis (eRA). However, a substantial proportion of patients still do not respond to MTX. <h3>Objectives</h3> To identify biomarkers for prediction of response to MTX. <h3>Methods</h3> We analysed a group of patients (n=135) with eRA from the Swedish Pharmacotherapy (SWEFOT) trial population. Baseline serum levels of 177 proteins were profiled using 380 antibodies in a suspension bead array format. Median fluorescent intensity (MFI) levels of the proteins were subsequently analysed for association with achievement of low 28-joint disease activity score (DAS28 ≤3.2) after 3 months of MTX therapy (primary outcome). Proteins that remained significant in multivariate model were analysed using receiver operating characteristic (ROC) curve analysis for cut-off definition of MFI and categorisation into high and low categories. Proportion of patients with primary outcome between the generated categories were compared using Chi-squared test. <h3>Results</h3> In multivariate analysis, serum levels of two of the 177 proteins at baseline, matrix metalloproteinase 7 (MMP-7) and alpha-chain of fibrinogen (FGA) were significantly different among patients who achieved or not achieved low DAS28 at 3 months. ROC curve analysis revealed AUC of 0.692 for MMP-7 and 0.699 for FGA (p&lt;0.001; figure 1A). ROC curve-based dichotomisation indicated that of patients with low versus high levels of either MMP-7 or FGA, 60% versus 24% and 58% versus 22%, respectively, achieved low DAS28 (p&lt;0.001; figure 1B and C). Among patients with low categories of both proteins, 79% achieved low DAS28 at 3 months, while only 18% of those in high categories for both proteins (p&lt;0.001; figure 1D). Validation in the COMBINE cohort with available MMP-7 data (whose concentration was measured by different method) did not confirm results from the SWEFOT trial. <h3>Conclusions</h3> Low levels of MMP-7 and FGA at baseline were associated with better clinical outcome in eRA patients. Following further characterisation, such biomarkers would be of high clinical relevance for the optimisation of treatment of RA. <h3>Disclosure of Interest</h3> K. Hambardzumyan: None declared, C. Hamsten: None declared, H. Idborg: None declared, L. Lourido: None declared, S. Saevarsdottir: None declared, P. Nilsson: None declared, R. van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, Pfizer, UCB, Consultant for: AbbVie, AstraZeneca, Biotest, BMS, Celgene, GSK, Janssen, Lilly, Novartis, Pfizer, UCB, P.-J. Jakobsson: None declared
AB1434-HPR Effects of core stability exercises on grip strength and manual dexterity in patients with chronic neck pain
Authors: M Soysal Tomruk, B. Kara, M. Tomruk, M. Arda
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> It is known that chronic neck pain causes sensorimotor disturbances. A reduction occurs in upper extremity functions due to pain and sensorimotor disturbances in chronic neck pain patients. Core stability exercises were thought to be effective in order to improve stability and muscular strength. However, there is insufficient information on whether core stability training improve grip strength and/or manual dexterity in chronic neck pain patients. <h3>Objectives</h3> The aim of this study was to investigate the effect of core stability exercises on grip strength and manual dexterity in patients with chronic neck pain. <h3>Methods</h3> Thirty six patients with chronic neck pain were enrolled. Grip strength and manual dexterity were evaluated by hand held dynamometer and Nine Hole Peg Test, respectively. Patients were randomly divided into supervised core stability exercise and home exercise group. Patients underwent twelve-week exercise training. All assessments were repeated at the 12th week. <h3>Results</h3> Grip strength and manual dexterity were significantly increased in both groups (p&lt;0.05). While both treatment methods had positive effects on grip strength and manual dexterity, core stability exercises were found to be more effective than home exercises to improve grip strength (p&lt;0.05) and manual dexterity (p=0.003 for right side, p=0.008 for left side). <h3>Conclusions</h3> Core stability exercises were more effective than home exercises to improve manual dexterity and grip strength. Core stability training should be added to rehabilitation approaches in order to enhance upper extremity functions in patients with chronic neck pain. <h3>References</h3> [1] Comparative effectiveness of Pilates and yoga group exercise interventions for chronic mechanical neck pain: quasi-randomised parallel controlled study. Dunleavy K, Kava K, Goldberg A, Malek MH, Talley SA, Tutag-Lehr V, Hildreth J. Physiotherapy. 2016Sep;102(3):236–42. doi: 10.1016/j.physio.2015.06.002. Epub 2015 Aug 13. [2] The effectiveness of a 6-week Pilates programme on outcome measures in a population of chronic neck pain patients: a pilot study. Mallin G, Murphy S. J Bodyw Mov Ther. 2013Jul;17(3):376–84 <h3>Disclosure of Interest</h3> None declared
SP0128 Finding the needle in the haystack and using it: galectin-9 as a biomarker in juvenile dermatomyositis
Authors: A. Van Royen-Kerkhof
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Juvenile dermatomyositis (JDM) is a rare systemic immune-mediated disease involving skin and muscle. A high disease burden exists with risk of both under- and overtreatment due to the lack of reliable biomarkers. <h3>Methods</h3> A multiplex immunoassay was performed in a discovery cohort for plasma levels of 45 proteins related to inflammation in 25 well-defined JDM patients, determined by clinical activity and treatment. Results were validated in two independent international external and internal validation cohorts (n=125). In a longitudinal cohort (n=30), the performance of this biomarker over time was assessed with a median 2.8 years follow-up. <h3>Results</h3> In the discovery cohort we found a clustering of 10 mediators of which Galectin-9 and CXCL10 distinguished best between active disease and remission. Both biomarkers had a strong correlation with clinical parameters (Spearman r with Physician's global assessment (PGA)=0.75 for both). This was confirmed in the validation cohorts (Spearman r=0.7 with PGA, for both). In the longitudinal cohort galectin-9 and CXCL10 correlated with disease activity over time, and elevated levels could predict flares several months before clinical symptoms. Both cross-sectionally and longitudinally, galectin-9 and CXCL10 outperformed creatine kinase activity. <h3>Conclusion</h3> Galectin-9 and CXCL10 are robust biomarkers for disease activity in JDM. A short-term implementation into clinical practice is feasible and can facilitate individualised treatment. <h3>Disclosure of Interest</h3> None declared
Abstract 16798: The Influence of Heart Failure With Preserved or Reduced Ejection Fraction on Relationships Between Cardiac Power and Stroke Work With VO2
Authors: Erik H Van Iterson, Eric M Snyder, Barry A Borlaug, Thomas P Olson
Journal: Circulation (2015)

Introduction: Invasive measurement of cardiac power (CP) and stroke work (SW) during exercise are robust indices of cardiac function and relate to syndrome severity and prognosis in heart failure patients with preserved (HFpEF) or reduced (HFrEF) ejection fraction. Because invasive measurement via catheterization laboratories are not always readily available, non-invasive cardiopulmonary exercise testing to estimate cardiac function is routinely performed in the clinical evaluation of HFpEF and HFrEF. However, it is unknown how VO 2 relates with CP and SW in HFpEF vs HFrEF. We compared relationships between CP and SW with VO 2 at rest and peak exercise in HFpEF vs HFrEF. Methods: 30 HFpEF and 32 HFrEF (EF: 62±2 vs 22±1%; males: 17 vs 30; age: 70±2 vs 55±2 yrs; BMI: 34±1 vs 28±1 kg/m 2 ; wt: 98±4 vs 86±3 kg (all p&lt;0.05)) participated in exercise testing during right heart catheterization. Oxygen consumption (VO 2 ) was measured continuously from rest to peak work. Invasive measures at rest and peak work included mean radial arterial pressure (MAP), right atrial pressure (RAP), and pulmonary capillary wedge pressure (PCWP). We calculated CP=(MAP–RAP) x Q I x 2.22х10 -3 and SW=(MAP–PCWP) x SV I x 0.133. Results: At rest, R 2 between VO 2 and CP or SW were not different between HFpEF (CP=0.41, SW=0.30) and HFrEF (CP=0.39, SW=0.15). Slopes did not differ significantly between HFpEF (CP=0.13, SW=0.01) and HFrEF (CP=0.16, SW=0.01) for regressions between VO 2 and CP or SW; but, fitted intercepts of the regression showed significantly higher intercepts in HFrEF (CP=0.89, SW=1.16) vs HFpEF (CP=0.05, SW=0.27) for VO 2 vs CP and SW, respectively. At peak exercise, R 2 between VO 2 and CP or SW were not different between HFpEF (CP=0.48, SW=0.64) and HFrEF (CP=0.70, SW=0.67). Slopes did not differ between HFpEF (CP=0.18, SW=0.02) and HFrEF (CP=0.15, SW=0.02) for regressions between VO 2 and CP or SW, whereas the fitted intercepts the slope of the regression were significantly higher in HFrEF (CP=5.1, SW=4.4) vs HFpEF (CP=3.2, SW=2.0) for VO 2 vs CP and SW, respectively. Conclusion: Our data suggest that despite lower VO 2 relative to CP and SW in HFpEF, both the strength of relationship and rate of increase in VO 2 relative to CP and SW are similar between HFpEF and HFrEF at rest and peak exercise.
Systematic analysis of dark and camouflaged genes reveals disease-relevant genes hiding in plain sight
Authors: Mark T. W. Ebbert, Tanner D. Jensen, Karen Jansen-West, Jonathon P. Sens, Joseph S. Reddy, Perry G. Ridge, John S. K. Kauwe, Veronique Belzil, Luc Pregent, Minerva M. Carrasquillo, Dirk Keene, Eric Larson, Paul Crane, Yan W. Asmann, Nilufer Ertekin-Taner, Steven G. Younkin, Owen A. Ross, Rosa Rademakers, Leonard Petrucelli, John D. Fryer
Journal: Genome biology (2019)

The human genome contains "dark" gene regions that cannot be adequately assembled or aligned using standard short-read sequencing technologies, preventing researchers from identifying mutations within these gene regions that may be relevant to human disease. Here, we identify regions with few mappable reads that we call dark by depth, and others that have ambiguous alignment, called camouflaged. We assess how well long-read or linked-read technologies resolve these regions. Based on standard whole-genome Illumina sequencing data, we identify 36,794 dark regions in 6054 gene bodies from pathways important to human health, development, and reproduction. Of these gene bodies, 8.7% are completely dark and 35.2% are ≥ 5% dark. We identify dark regions that are present in protein-coding exons across 748 genes. Linked-read or long-read sequencing technologies from 10x Genomics, PacBio, and Oxford Nanopore Technologies reduce dark protein-coding regions to approximately 50.5%, 35.6%, and 9.6%, respectively. We present an algorithm to resolve most camouflaged regions and apply it to the Alzheimer's Disease Sequencing Project. We rescue a rare ten-nucleotide frameshift deletion in CR1, a top Alzheimer's disease gene, found in disease cases but not in controls. While we could not formally assess the association of the CR1 frameshift mutation with Alzheimer's disease due to insufficient sample-size, we believe it merits investigating in a larger cohort. There remain thousands of potentially important genomic regions overlooked by short-read sequencing that are largely resolved by long-read technologies.
Expanding Usutu virus circulation in Italy: detection in the Lazio region, central Italy, 2017 to 2018
Authors: Fabrizio Carletti, Francesca Colavita, Francesca Rovida, Elena Percivalle, Fausto Baldanti, Ida Ricci, Claudio De Liberato, Francesca Rosone, Francesco Messina, Eleonora Lalle, Licia Bordi, Francesco Vairo, Maria Rosaria Capobianchi, Giuseppe Ippolito, Giuseppina Cappiello, Alberto Spanò, Silvia Meschi, Concetta Castilletti
Journal: Eurosurveillance (2019)

Blood donation screening for West Nile virus (WNV) was mandatory in the Lazio region in 2017 and 2018 (June-November) according to the national surveillance plan. In these years, all five donations reactive in WNV nucleic acid amplification tests harboured instead Usutu virus (USUV). Clade 'Europe 2' was identified in four blood donations and a 2018 mosquito pool. The cocirculation of WNV and USUV in Lazio warrants increased laboratory support and awareness of possible virus misidentification.
Isolation and Validation of the First Functional HLA-a*01:01 Restricted EBV-LMP2 Specific T Cells for Treatment of EBV Associated Type II/III Lymphomas
Authors: Wesley Huisman, Lieve E. van der Maarel, Lois Hageman, Rob C.M. de Jong, Derk Amsen, J.H. Frederik Falkenburg, Inge Jedema
Journal: Blood (2018)
Sertraline or placebo in chronic breathlessness? Lessons from placebo research
Authors: Kyle Pattinson, Vishvarani Wanigasekera
Journal: European Respiratory Journal (2019)

We were fascinated by the recent paper from Currow et al . [1], which described the largest randomised controlled trial of an antidepressant in the treatment of chronic refractory breathlessness. This study was important as there are few pharmacological treatments available for chronic breathlessness. In this group there is an unmet clinical need for treatments that target symptoms. The study's theoretical basis was well supported by preliminary data. However, no difference was observed between sertraline and placebo for the primary outcome measure, the improvement in breathlessness intensity. Harnessing the placebo response may benefit patients with chronic breathlessness <http://ow.ly/1BTK30naRZc>
THU0477 Factors associated with the initiation of treatment after fragility fracture in a fracture liaison service
Authors: A. Saavedra, A. Naranjo, S. Ojeda, R. Lopez, A. Molina, C. Alonso, I. Bernardos, C. Rodriguez-Lozano
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Adherence to treatment in osteoporosis (OP) is not adequate, so that in the first year the percentage of suspensions is between 30% and 50%, up to an adherence of 20% at 3 years. In 2012, we started in Gran Canaria a Fracture Liaison Service (FLS). <h3>Objectives</h3> To describe the factors associated to an effective initiation of treatment after the baseline visit to our FLS. <h3>Methods</h3> Prospective observational study that consists of: 1) training of primary care physicians (GP), 2) capture of patients; 3) baseline visit: questionnaire including FRAX; 4) Bone densitometry; 5) patient education by a Nurse with special attention to adherence; 6) referral to GP with a report with management recommendations; those with multiple fractures or who require parenteral therapy were referred to rheumatology; and 7) follow-up by telephone survey to check whether the treatment was taking and confirmation of the prescription in the electronic records (both of which are necessary to consider an effective start of treatment). The variables included were: sex, age, type of fracture, use of previous bisphosphonate, type of prescribed treatment, prescribing physician and causes of non-adherence. <h3>Results</h3> Up to December 2017, the adherence of 887 patients with fragility fractures to whom a bisphosphonate or equivalent was prescribed, was recorded. Treatment was initiated in the following 3 months by 74% (n=656) of patients. The following variables were associated with the initiation of treatment: female sex, previous treatment with antiresorptives, prescription of denosumab vs bisphosphonate and treatment precribed by a rheumatologist vs GP (table 1). The causes of not initiating or withdrawing the treatment at 3 months are shown in table 2. In the regression analysis, we found a significant association with the effective initiation of treatment with a pevious treatment with bisphosphonate (p&lt;0.01), initiation of treatment by the rheumatologist (p=0.01) and prescription of denosumab vs bisphosphonate (p&lt;0.01) <h3>Conclusions</h3> 74% of patients seen in the FLS start treatment within 3 months of the baseline visit. The factors associated with the initiation of therapy were prior antiresorptive treatment, denosumab prescription and initial prescription by the rheumatologist. The reason of non adherence in half of the cases is the GP's refusal to initiate or continue the FLS recommendation. <h3>Disclosure of Interest</h3> None declared
Medical Conditions Among Survivors of Adolescent and Young Adult Non-Hodgkin Lymphoma (NHL), Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML)
Authors: Theresa H.M. Keegan, Lori S Muffly, Qian Li, Elysia Alvarez, Ann M Brunson, Marcio Malogolowkin, Ted Wun
Journal: Blood (2018)
Induced packaging of mRNA into polyplex micelles by regulated hybridization with a small number of cholesteryl RNA oligonucleotides directed enhanced in vivo transfection
Authors: Naoto Yoshinaga, Satoshi Uchida, Mitsuru Naito, Kensuke Osada, Horacio Cabral, Kazunori Kataoka
Journal: Biomaterials (2019)
Hierarchically targetable polysaccharide-coated solid lipid nanoparticles as an oral chemo/thermotherapy delivery system for local treatment of colon cancer
Authors: Ming-Yin Shen, Te-I Liu, Ting-Wei Yu, Reesha Kv, Wen-Hsuan Chiang, Yuan-Chung Tsai, Hsin-Hung Chen, Sung-Chyr Lin, Hsin-Cheng Chiu
Journal: Biomaterials (2019)
Abstract 15186: Shock Severity and Cytokine Profiles in Adult VA-ECMO Subjects With and Without Antecedent CPR
Authors: Joshua C Reynolds, Alastair Proudfoot, Nabin K Shrestha, Stefan Jovinge
Journal: Circulation (2017)

Introduction: ECMO and post-cardiac arrest syndrome both yield complex inflammatory responses. We compared clinical features and cytokine profiles (CYTO) between VA-ECMO patients with/without antec...
Detailed Time Course of Decline in Serum C-Peptide Levels in Anti–Programmed Cell Death-1 Therapy–Induced Fulminant Type 1 Diabetes
Authors: Daigo Saito, Yoichi Oikawa, Yuya Yano, Yuichi Ikegami, Atsushi Satomura, Masashi Isshiki, Susumu Kurihara, Ikuo Inoue, Mitsuhiko Noda, Akira Shimada
Journal: Diabetes Care (2019)

Fulminant type 1 diabetes (FT1D) is a novel subtype of type 1 diabetes (T1D) and is characterized by a relatively low glycated hemoglobin (HbA1c) level at onset, despite the abrupt occurrence of marked hyperglycemia with ketosis or ketoacidosis (1). Recent studies have shown that anti–programmed cell death (PD)-1/anti–PD-ligand 1 (PD-L1) therapy for malignancies leads to the development of T1D including FT1D (2–4). In typical FT1D, insulin secretion capacity is completely exhausted within ∼7 days after the onset (1); in some cases, a rapid loss of insulin secretion was observed during 2 days prior to onset of diabetic ketoacidosis (DKA) (5). Meanwhile, the detailed time course of insulin secretion capacity in anti–PD-1 therapy–induced FT1D has not yet been reported.

We present a case of an 82-year-old Japanese man with squamous cell cancer of the lung, who had received multiple courses of anti–PD-1 immunotherapy (pembrolizumab) every 3 weeks for ∼12 months. Written informed consent was obtained from the participant. On the day of the 16th course of anti–PD-1 therapy, his casual plasma glucose and HbA1c levels were 106 mg/dL and 5.8% (40 mmol/mol), respectively. However, a blood test performed on the scheduled day of the 17th course revealed his casual plasma glucose was 432 mg/dL; thus, he was immediately hospitalized without …