tbuckley/cabot-search huggingface dataset:
Cardiac troponins: from myocardial infarction to chronic disease
Authors: Kyung Chan Park, David C Gaze, Paul O Collinson, Michael S Marber
Journal: Cardiovascular Research (2017)

Elucidation of the physiologically distinct subunits of troponin in 1973 greatly facilitated our understanding of cardiac contraction. Although troponins are expressed in both skeletal and cardiac muscle, there are isoforms of troponin I/T expressed selectively in the heart. By exploiting cardiac-restricted epitopes within these proteins, one of the most successful diagnostic tests to date has been developed: cardiac troponin (cTn) assays. For the past decade, cTn has been regarded as the gold-standard marker for acute myocardial necrosis: the pathological hallmark of acute myocardial infarction (AMI). Whilst cTn is the cornerstone for ruling-out AMI in patients presenting with a suspected acute coronary syndrome (ACS), elevated cTn is frequently observed in those without clinical signs indicative of AMI, often reflecting myocardial injury of 'unknown origin'. cTn is commonly elevated in acute non-ACS conditions, as well as in chronic diseases. It is unclear why these elevations occur; yet they cannot be ignored as cTn levels in chronically unwell patients are directly correlated to prognosis. Paradoxically, improvements in assay sensitivity have meant more differential diagnoses have to be considered due to decreased specificity, since cTn is now more easily detected in these non-ACS conditions. It is important to be aware cTn is highly specific for myocardial injury, which could be attributable to a myriad of underlying causes, emphasizing the notion that cTn is an organ-specific, not disease-specific biomarker. Furthermore, the ability to detect increased cTn using high-sensitivity assays following extreme exercise is disconcerting. It has been suggested troponin release can occur without cardiomyocyte necrosis, contradicting conventional dogma, emphasizing a need to understand the mechanisms of such release. This review discusses basic troponin biology, the physiology behind its detection in serum, its use in the diagnosis of AMI, and some key concepts and experimental evidence as to why cTn can be elevated in chronic diseases.
FRI0141 Left ventricular concentric remodeling is more prevalent in rheumatoid arthritis: a case-control study
Authors: DΆ Galarza-Delgado, JR Azpiri-Lόpez, IJ Colunga-Pedraza, FJ Torres-Quintanilla, RE Ramos-Cázares, A Valdovinos-Bañuelos, A Martínez-Moreno, RI Arvizu-Rivera, R Vera-Pineda, JA Cárdenas-de la Garza, MA Garza-Elizondo, MA Benavides-González, JA Silva-Ortiz
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) have a higher risk to develop cardiovascular complications than general population (1), leading to a decrease in life expectancy of 3 to 10 years (2). RA is associated to increased left ventricle mass, pericardial effusion and diastolic dysfunction (3). <h3>Objectives</h3> The aim of this study was to assess the structure and function of the left ventricle in patients with RA and compare the results with matched controls. <h3>Methods</h3> We designed an observational cross-section case-control study. Patients diagnosed with RA according to the 1987 ACR and/or 2010 ACR/EULAR classification criteria, 40–75 years old, with no overlap syndromes, atherosclerotic cardiovascular disease or hypertension were included. Subjects for the control group were matched by sex, age and comorbidities. A board-certified cardiologist performed a transthoracic echocardiogram. <h3>Results</h3> We included a total of 44 RA-patients and 26 control subjects. Table 1 summarizes the demographic characteristics for each group. Left ventricular concentric remodeling (LVCR), defined as a relative wall thickness (RWT) &gt;0.42 cm and a left ventricular mass index (LVMI) ≤95 gm/m<sup>2</sup> in women and ≤115 gm/m<sup>2</sup> in men, was found in 14 patients (32.6%) of the RA-group and 2 subjects (8%) of the control group; this difference was statistically significant (p=0.021). When we analyzed general abnormalities of left ventricle (either LVCR or left ventricular concentric hypertrophy [RWT &gt;0.42 cm and LVMI &gt;95 gm/m<sup>2</sup> in women, &gt;115 gm/m<sup>2</sup> in men]) we found 15 RA patients (34.1%) with abnormalities and 3 subjects in the control group (11.5%) (p=0.037). There were no statistically significant differences among the groups in LVMI, diastolic dysfunction, global longitudinal strain or ejection fraction. <h3>Conclusions</h3> Left ventricle concentric remodeling is more prevalent in RA-patients when compared to controls. Further research is needed to determine the impact of these findings in the clinical prognosis of RA-patients. <h3>References</h3> Solomon DH, Curhan GC, Rimm EB, Cannuscio CC, Karlson EW. Cardiovascular risk factors in women with and without rheumatoid arthritis. Arthritis &amp; Rheumatism. 2004;50(11):3444–9. Myasoedova E, Davis JM, Crowson CS, Gabriel SE. Epidemiology of Rheumatoid Arthritis: Rheumatoid Arthritis and Mortality. Current Rheumatology Reports. 2010;12(5):379–85. Corrao S, Messina S, Pistone G, Calvo L, Scaglione R, Licata G. Heart involvement in Rheumatoid Arthritis: Systematic review and meta-analysis. International Journal of Cardiology. 2013;167(5):2031–8. <h3>Disclosure of Interest</h3> None declared
Prevention of C5aR1 signaling delays microglial inflammatory polarization, favors clearance pathways and suppresses cognitive loss
Authors: Michael X. Hernandez, Shan Jiang, Tracy A. Cole, Shu-Hui Chu, Maria I. Fonseca, Melody J. Fang, Lindsay A. Hohsfield, Maria D. Torres, Kim N. Green, Rick A. Wetsel, Ali Mortazavi, Andrea J. Tenner
Journal: Molecular Neurodegeneration (2017)

Pharmacologic inhibition of C5aR1, a receptor for the complement activation proinflammatory fragment, C5a, suppressed pathology and cognitive deficits in Alzheimer's disease (AD) mouse models. To validate that the effect of the antagonist was specifically via C5aR1 inhibition, mice lacking C5aR1 were generated and compared in behavior and pathology. In addition, since C5aR1 is primarily expressed on cells of the myeloid lineage, and only to a lesser extent on endothelial cells and neurons in brain, gene expression in microglia isolated from adult brain at multiple ages was compared across all genotypes. C5aR1 knock out mice were crossed to the Arctic AD mouse model, and characterized for pathology and for behavior performance in a hippocampal dependent memory task. CX3CR1GFP and CCR2RFP reporter mice were bred to C5aR1 sufficient and knockout wild type and Arctic mice to enable sorting of microglia (GFP-positive, RFP-negative) isolated from adult brain at 2, 5, 7 and 10 months of age followed by RNA-seq analysis. A lack of C5aR1 prevented behavior deficits at 10 months, although amyloid plaque load was not altered. Immunohistochemical analysis showed no CCR2+ monocytes/macrophages near the plaques in the Arctic brain with or without C5aR1. Microglia were sorted from infiltrating monocytes (GFP and RFP-positive) for transcriptome analysis. RNA-seq analysis identified inflammation related genes as differentially expressed, with increased expression in the Arctic mice relative to wild type and decreased expression in the Arctic/C5aR1KO relative to Arctic. In addition, phagosomal-lysosomal gene expression was increased in the Arctic mice relative to wild type but further increased in the Arctic/C5aR1KO mice. A decrease in neuronal complexity was seen in hippocampus of 10 month old Arctic mice at the time that correlates with the behavior deficit, both of which were rescued in the Arctic/C5aR1KO. These data are consistent with microglial polarization in the absence of C5aR1 signaling reflecting decreased induction of inflammatory genes and enhancement of degradation/clearance pathways, which is accompanied by preservation of CA1 neuronal complexity and hippocampal dependent cognitive function. These results provide links between microglial responses and loss of cognitive performance and, combined with the previous pharmacological approach to inhibit C5aR1 signaling, support the potential of this receptor as a novel therapeutic target for AD in humans.
FRI0580 Predict sarcopenia by sonoelastography of quadriceps muscle in osteoporotic patients
Authors: Y-C Chen, C-H Ko
Journal: Annals of the Rheumatic Diseases (2017)

secondary osteoporosis was detected.Serum vitamin D concentration was <30 ng/ml in 5 patients, including 2 with concentration <10 ng/ml.Conclusions: Our study reveals that odontoid fractures mainly occur in elderly osteoporotic patients after a low energy impact.Although WHO osteoporosis definition excludes cervical fractures, odontoid fracture may be considered as an osteoporotic fracture.Further studies are required to confirm these results.
AB1183 Patient's education in the administration of subcutaneous drugs in the rheumatology day-care hospital units
Authors: A Erra, A Fagil, L Lόpez
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatology Day-Care Hospital Unit (DHU) is defined as a hospital care for a few hours with the objective to do diagnosis, clinical trials and/or multiple test, patient education and treatments that cannot be done in the outpatient clinic, but which do not justify the complete stay in the hospital <h3>Objectives</h3> Analyze the number of visits that one patient needs in the Rheumatology-DHU to learn the self-administration of a subcutaneous drug. To evaluate if there are differences between the numbers of visits made in Rheumatology-DHU for the different drugs, and between the different age groups of the patients. <h3>Methods</h3> All patients who were prescribed a subcutaneous drug (except denosumab) during the period January 2015 - December 2016 were referred to Rheumatology-DHU. The nurse gave instructions, she supervised the patient9s learning and she decided if the patients needed a new control in Rheumatology-DHU. The following data were recorded: sex, age, diagnosis, drug, number of visits each patient made in Rheumatology-DHU, reason for new visit to Rheumatology-DHU in patients who had already been discharged and adherence to treatment. <h3>Results</h3> 101 patients were visited in Rheumatology-DHU (8 were referred twice for education of different drugs). 79 were women (78%) and 22 men (22%). Mean age (MA) of 65 +/- 17 years (SD). A total of 238 visits were made in Rheumatology-DHU. Adherence to treatment was 98.2%. Six patients (5.5%) required a new referral to Rheumatology-DHU: 1 for poor adherence to treatment (ADA), 3 for skin lesions (2 MTX and 1 GOL), 2 supervise the treatment (1 CER and 1 MTX). In 9% of the patients, the education was done to a reference person and not to the patient himself. The number of visits in the Rheumatology-DHU were: 1 in 26 patients (MS of 66 +/- 19.6 years), 2 in 59 patients (MS 65 +/- 18); 3 in 13 patients (MS 64 +/- 13); 4 in 6 patients (MS 67 +/- 14); 5 in 2 patients (MS 68 +/- 17), 6 in 2 patients (MS 70 +/- 22), 9 in 1 patient (47 years). We analyzed PTH and MTX groups (because they had the highest number of patients) and we observed that in the PTH group 82% required ≤2 visits, 18%&gt; of 2 visits. Patients in MTX group: 77% ≤2 visits and 23%&gt;2 education visits. There weren9t significant differences between the two groups (p=0.576). <h3>Conclusions</h3> Adherence to treatment in patients who are referred to Rheumatology-DHU to learn the self-administration of a subcutaneous drug is very high. The new visits in Rheumatology-DHU for doubts or side effects were few. Patients on PTH treatment, who were older, didn9t require a higher number of visits or more new referrals to Rheumatology-DHU. Therefore, age is not a limiting factor for the right learning of patients. The patient9s education by nurse in Rheumatology-DHU is necessary for the right control of our patients <h3>Disclosure of Interest</h3> None declared
Cold versus hot endoscopic mucosal resection for nonpedunculated colorectal polyps sized 6–10 mm: a randomized trial
Authors: Vasilios Papastergiou, Konstantina Paraskeva, Maria Fragaki, Ioannis Dimas, Emmanouil Vardas, Angeliki Theodoropoulou, Nicoletta Mathou, Athanasios Giannakopoulos, Konstantinos Karmiris, Afroditi Mpitouli, Dimitra Apessou, Linda Giannikaki, John Karagiannis, Grigorios Chlouverakis, Gregorios Paspatis
Journal: Endoscopy (2017)

Abstract Background and study aims Cold snare polypectomy is an established method for the resection of small colorectal polyps; however, significant incomplete resection rates still leave room for improvement. We aimed to assess the efficacy of cold snare endoscopic mucosal resection (CS-EMR), compared with hot snare endoscopic mucosal resection (HS-EMR), for nonpedunculated polyps sized 6 – 10 mm. Patients and methods This study was a dual-center, randomized, noninferiority trial. Consecutive adult patients with at least one nonpedunculated polyp sized 6 – 10 mm were enrolled. Eligible polyps were randomized (1:1) to be treated with either CS-EMR or HS-EMR. Both methods involved submucosal injection of a methylene blue-tinted normal saline solution. The primary noninferiority end point was histological eradication evaluated by postpolypectomy biopsies (noninferiority margin – 10 %). Secondary outcomes included occurrence of intraprocedural bleeding, clinically significant postprocedural bleeding, and perforation. Results Among 689 patients screened, 155 patients with 164 eligible polyps were included (CS-EMR n = 83, HS-EMR n = 81). The overall rate of histological complete resection was 92.8 % in the CS-EMR group and 96.3 % in the HS-EMR group (difference 3.5 %; 95 % confidence interval [CI] – 4.15 to 11.56), showing noninferiority of CS-EMR compared with HS-EMR. CS-EMR was shown to be noninferior both for polyps measuring 6 – 7 mm (CS-EMR 93.3 %; HS-EMR 100 %; 95 %CI – 7.95 to 21.3) and those of 8 – 10 mm (92.5 % vs. 94.7 %, respectively; 95 %CI – 7.91 to 13.16). Rates of intraprocedural bleeding were similar between the two groups (CS-EMR 3.6 %, HS-EMR 1.2 %; P = 0.30). No clinically significant postprocedural bleeding or perforation occurred in either group. Conclusions CS-EMR appears to be a valuable modification of the standard cold snare technique, obviating the need to use diathermy for nonpedunculated colorectal polyps sized 6 – 10 mm.
Current status of and strategies for hepatitis C control in South Korea
Authors: Beom Kyung Kim, Eun Sun Jang, Jeong Han Kim, Soo Young Park, Song Vogue Ahn, Hyung Joon Kim, Do Young Kim
Journal: Clinical and Molecular Hepatology (2017)

Chronic hepatitis C (CHC) is caused by hepatitis C virus (HCV) infection. HCV infection causes acute hepatitis, and the majority of those infected progress to chronic hepatitis, and some of them develop cirrhosis and hepatocellular carcinoma. Transmission of HCV is parenteral, and the major transmission routes include drug abuse, insecure injections or medical procedures, contaminated syringes or needles, sexual contact with an HCV-infected person, vertical infection of newborns by infected mothers, the transfusion of blood or blood products contaminated with viruses, and organ transplants. As no vaccine against HCV is available, HCV management involves blocking routes of transmission transmission, screening for HCV infection, and protecting liver disease progression by treatment. Highly potent oral direct antiviral agents are now available. Therefore, early detection through nation-wide screening program and appropriate treatment should be implemented to improve the quality of life of patients with HCV. Furthermore, for the effective HCV control in South Korea, The organization of an 'integrated national viral hepatitis control system' is desirable. Keywords: Hepatitis C virus; Status; Control
BRCAness in non-small cell lung cancer (NSCLC).
Authors: Saiama Naheed Waqar, Siddhartha H. K. Devarakonda, Loren S. Michel, Leonard B. Maggi, Mark Watson, Kalin Guebert, Danielle Carpenter, Barry P Sleckman, Ramaswamy Govindan, Daniel Morgensztern
Journal: Journal of Clinical Oncology (2014)

11033 Background: Germline mutations in the BRCA1 and BRCA2 DNA repair genes confer susceptibility to breast and ovarian cancer, and are targets for PARP inhibitors. The term “BRCAness” broadly refers to somatic molecular defects in the cellular DNA repair machinery, resulting in a phenotype similar to that caused by BRCA germline mutations. We evaluated data from The Cancer Genome Atlas (TCGA) for molecular alterations in double strand DNA repair genes in NSCLC. Methods: We examined somatic molecular alterations in 20 homologous recombination (HR) and 16 Fanconi anemia (FA) genes in 230 lung adenocarcinoma (LUAD) and 178 squamous cell carcinoma (SQCC) samples from TCGA data using cBio portal. Alterations were classified into homozygous deletion, mutation, and amplification. Tendency towards co-occurrence and mutual exclusivity of mutations in these genes was described using odds ratios (OR) and calculated by Fisher’s exact test using α = 0.05. Results: Somatic molecular alterations involving at least 1 HR or FA gene were observed in 121 (53%) of LUAD and 90 (51%) of SQCC respectively. The most common homozygous deletions noted were in RAD51 (3%) in LUAD and XRCC1 (1%) in SQCC. Frequent somatic gene mutations in BRCA2 (5%), BRCA1 (3%), RAD54B (3%) and BRIP1 (3%) were observed in LUAD, including the well-known nonsense S3376 and S2695 mutations in BRCA2. BRCA1 and RAD51D mutations tended to co-occur (OR >10; p=0.03), while BRCA2 mutations tended to co-occur with FANCB (OR >10; p=0.02) and RAD54L (OR >10; p=0.01) in LUAD. Commonly observed somatic mutations in SQCC included the following genes: BRCA1 (6%), BRCA2 (6%), FANCA (3%) and PALB2 (3%), including the known Q94 and K1160 nonsense mutations in BRCA1 and nonsense mutations Q499 and E187 in BRCA2. BRCA1 and PALB2 gene mutations tended to co-occur (OR>10; p=0.001) in SQCC. Amplifications were most commonly noted in XRCC2, NBN, RBBP8 and C19ORF40 in LUAD (2% each), and FANCG, FANCL, C19ORF40 in SQCC (4% each). Conclusions: BRCAness is commonly observed in NSCLC and may be a target for PARP inhibition in molecularly selected patient populations.
Current status of allergen immunotherapy
Authors: R. A. Thompson, J. Bousquet, F. S. Cohen, P. C. Frei, L. Jager, P. H. Lambert, M. H. Lessof, R. H. Loblay, H. J. Malling, P. S. Norman, A. L. De Weck, B. Weeke
Journal: The Lancet (1989)
Safety and Feasibility of Administration of High Doses of Ex Vivo Expanded NK Cells for Prevention of Disease Relapse after Transplantation for Patients with Myeloid Malignancies - Final Results of a Phase I Clinical Trial
Authors: Stefan O. Ciurea, Dean A. Lee, Cecele Denman, Jolie Schafer, Roland L Bassett, Kai Cao, Gabriela Rondon, Julianne Chen, Doris Soebbing, Dana B. Willis, Sairah Ahmed, Qaiser Bashir, Partow Kebriaei, Issa F. Khouri, Betul Oran, Simrit Parmar, Uday R. Popat, Chitra Hosing, Eric Yvon, Katayoun Rezvani, Elizabeth J. Shpall, Richard E. Champlin
Journal: Blood (2016)
FRI0277 ANTI-SSA antibody status in combination with ultrasound of major salivary glands: a shortcut in the classification of primary sjÖgren's syndrome?
Authors: E Mossel, K Delli, JF Van Nimwegen, AJ Stel, FGM Kroese, FKL Spijkervet, A Vissink, S Arends, H Bootsma
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Ultrasound of major salivary glands (sUS) is an upcoming diagnostic method to assess the involvement of major salivary glands in primary Sjögren9s syndrome (pSS). In the AECG, ACR and recently published ACR-EULAR criteria, a positive salivary gland biopsy and/or presence of anti-SSA antibodies are necessary to classify a patient as pSS, while sUS is not included as a diagnostic item. <h3>Objectives</h3> To assess whether combining anti-SSA antibody status with sUS outcome can predict classification of patients as pSS in our inception cohort study. <h3>Methods</h3> Consecutive outpatients clinically suspected with pSS underwent sUS of the parotid and submandibular glands. Parenchymal echogenicity, homogeneity, hypoechogenic areas, hyperechogenic reflections and clearness of salivary gland border were scored according to the Hocevar scoring system (total score 0–48).<sup>1</sup> Positive sUS was defined as total score ≥15. Patients underwent a diagnostic work up according to the AECG, ACR and ACR-EULAR criteria. We analyzed the predictive value of the combination of anti-SSA antibody status and sUS outcome for classification as pSS or non-pSS. Separate analyses were done considering either i) parotid gland biopsy or ii) labial gland biopsy as an item, when applying these classification criteria. <h3>Results</h3> Anti-SSA antibody status was positive in 53 (51%) patients and sUS was positive in 40 (39%) patients. When parotid gland biopsy outcome was considered as an item of the criteria, 45 of 97 patients were classified as pSS according to the AECG, 44 of 97 according to the ACR and 52 of 99 according to the ACR-EULAR criteria. The combination of presence of anti-SSA antibodies with positive sUS showed a very high positive predictive value for classification as pSS (94–97%) and the combination of absence of anti-SSA antibodies with negative sUS highly excludes classification (negative predictive value 98–100%). When labial gland biopsy outcome was considered as an item of the criteria, 49 of 96 patients were classified as pSS according to the AECG, 43 of 93 according to the ACR and 55 of 97 according to the ACR-EULAR criteria. The combination of presence of anti-SSA antibodies with positive sUS showed a high positive predictive value for classification as pSS (94–97%). However, the combination of absence of anti-SSA antibodies with negative sUS did not per se exclude classification (negative predictive value 89–93%). <h3>Conclusions</h3> In our prospective inception cohort study derived from daily clinical practice, the combination of presence of anti-SSA antibodies and positive sUS outcome highly predicts classification as pSS according to the AECG, ACR and ACR-EULAR classification criteria. <h3>References</h3> Hocevar et al. Rheumatology (Oxford) 2005;44:768–72. <h3>Disclosure of Interest</h3> None declared