tbuckley/cabot-search huggingface dataset:
Abstract 14795: Strain Imaging Corrected by RR-interval is a Superior Predictor of Outcome in Patients With Atrial Fibrillation
Authors: Maria Dons, Jan S Jensen, Flemming J Olsen, Martina C de Knegt, Thomas Fritz-Hansen, Tor Biering-Sørensen
Journal: Circulation (2015)

Aims: This study evaluates the prognostic value of strain in patients with atrial fibrillation (AF) and suggests a novel approach on how to take into account the varying heart cycle lengths in AF. Methods: Echocardiograms from 204 patients with AF during examination were analyzed. Peak global longitudinal strain (GLS) was averaged from the apical 4-chamber, 2-chamber and long axis view. To adjust for the varying heart cycle lengths, we indexed the strain measurements with the square root of the RR-interval, (GLS/√(RR)). The combined end-point included incident heart failure, stroke, myocardial infarction and all-cause mortality. Results: During a median follow-up of 2.4 years, 82 patients (40%) reached the combined endpoint. Significant predictors at baseline included age (p&lt;0.001) and diabetes mellitus (p=0.014). Decreasing GLS/√(RR) was significantly associated with the combined endpoint, and the risk of reaching the endpoint increased significantly per 1%/sec1/2 decrease in strain (HR 1.13, 95% CI 1.07-1.20, p&lt;0.001), especially in the patients with the lowest values of GLS/√(RR)(Figure 1). GLS/√(RR) remained an independent predictor even after adjustment for various risk factors, LVEF and E/e’ (HR 1.10, 95% CI: 1.02-1.19, p=0.017). In contrast, GLS did not remain a significant predictor after adjusting for the same variables (p=0.07), neither did LVEF (p=0.11). Besides being associated with an adverse outcome, decreasing values of GLS/√(RR) was associated with lower LVEF, larger LV mass and larger LV dimension (p&lt;0.001 for all). Conclusion: Decreasing GLS/√(RR) was significantly associated with increased risk of reaching the combined endpoint and remained an independent predictor after multivariable adjustment. Indexing the strain values with the square root of the RR-interval (GLS/√(RR)) can counteract the variable cycle length in AF patients and GLS/√(RR) offers a more convincing risk-stratification assessment in AF patients compared to GLS.
Abstract 12388: Left Ventricular Layer Torsion in Hypertensive Patients using One-beat Real-time Three-dimensional Speckle Tracking Echocardiography With High Volume Rates
Authors: Hirotaka Miwa, Masanori Kawasaki, Ryuhei Tanaka, Maki Nagaya, Shingo Minatoguchi, Takahiro Ueno, Hidemaro Sato, Shigeki Sawada, Ryota Watanabe, Takashi Kato, Takeshi Hirose, Makoto Iwama, Mayumi Kaneda, Koji Ono, Toshiyuki Noda, Sachiro Watanabe, Shinya Minatoguchi
Journal: Circulation (2015)

Background: Left ventricle (LV) is composed of three myocardial layers and LV torsion caused by inner and outer oblique muscle contraction plays an important role in squeezing blood out of the heart. However, LV layer torsion has not been examined using echocardiography. We sought to examine LV layer torsion and the relation between layer torsion and systolic function in hypertension (HTN) by one-beat 3-dimensional speckle tracking echocardiography (3D-STE). Methods: We enrolled 31 controls (age 65±12), 47 HTN without hypertrophy (LVH) (age 67±12), 47 HTN with LVH (age 70±11) and 37 patients with hypertensive heart failure (HHF) (age 74±15) to characterize LV layer torsion {endocardium (end), midwall (mid) and epicardium (epi)} using 3D-STE with volume rate of 70-80vps. LV twist was defined as maximum difference in rotation angle between base and apex (°). LV torsion was defined as twist / long axis length (°/cm). Time to peak torsion was expressed as % systole by dividing the time by total systolic time. Results: LV ejection fraction (EF) by STE in HHF decreased (control; 58±6, HTN without LVH; 56±9, HTN with LVH; 55±11, HHF; 39±11* %, *p&lt;0.05 vs control). The amplitudes of peak torsion at 3 layers were correlated with LVEF (end: r=0.30, mid: r=0.26, epi: r=0.27, p&lt;0.001). End peak torsion was significantly greater than the corresponding mid and epi torsion by 50 % and 78 %. LV torsion in HHF was the lowest in all 3 layers among 4 groups. The decreasing LV layer torsion from end to epi was observed in 4 groups (Control: end; 2.5±0.4, mid; 1.2±0.2, epi; 0.5±0.2 °/cm. HTN without LVH: end; 2.5±0.5, mid; 1.3±0.3, epi; 0.6±0.3 °/cm. HTN with LVH: end; 2.6±0.5, mid; 1.3±0.3, epi; 0.6±0.3 °/cm. HHF: end; 2.2±0.3*, mid; 1.1±0.2*, epi; 0.4±0.2* °/cm, *p&lt;0.05 vs control). Time to peak torsion is earliest at end layer in HHF and latest at epi layer in HTN with LVH (85±13 % systole and 97±5 % systole, p&lt;0.05). Conclusion: The amplitude of LV torsion assessed by 3D-STE was greater in endocardium and followed by midwall and epicardium and the smallest in all 3 layers of HHF. The difference in LV torsion among 3 layers seemed to diminish in association with LV systolic dysfunction. Assessment of layer torsion may be useful to understand mechanism of LV systolic function and to detect LV layer damage in HTN.
Author Correction: Transcriptional network analysis implicates altered hepatic immune function in NASH development and resolution
Authors: Joel T. Haas, Luisa Vonghia, Denis A. Mogilenko, An Verrijken, Olivier Molendi-Coste, Sébastien Fleury, Audrey Deprince, Artemii Nikitin, Eloïse Woitrain, Lucie Ducrocq-Geoffroy, Samuel Pic, Bruno Derudas, Hélène Dehondt, Céline Gheeraert, Luc Van Gaal, Ann Driessen, Philippe Lefebvre, Bart Staels, Sven Francque, David Dombrowicz
Journal: Nature Metabolism (2019)
AB0271 FACTORS ASSOCIATED WITH HOSPITAL ADMISSIONS MORTALITY IN RHEUMATOID ARTHRITIS PATIENTS IN SPAIN. (TREND-AR STUDY)
Authors: Ramón Mazzucchelli, Elia Perez-Fernandez, Javier Quirós, Virginia Villaverde, Alberto García-Vadillo, Marina Peña, Carmen Barbadillo, Cristina Macía-Villa, Jose Luis Morell Hita, Hilda Godoy, Manuel Fernandez-Prada, María Galindo-Izquierdo, Angeles Herranz Varela, Concepción Morado Quiroga, María Espinosa, Cristina Martinez-Prada, Natalia Crespí-Villarías
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> There have been significant changes in the management of rheumatoid arthritis (RA) during the past 20 years. The potential impact of these changes on hospital admissions mortality is unknown. <h3>Objectives</h3> To analyse the factors associated with hospital admissions mortality in rheumatoid arthritis patients in Spain from 1999 to 2015. <h3>Methods</h3> This is a retrospective population study. We have analized a national administrative database that includes a Minimum Basic Data Set (MBDS) of hospital admissions of RA patients during the period 1999 to 2015. We studied all the cases of hospital admissions mortality. Patients were identified by concatenation of clinical record number and birth date. The analyzed factors were identified by the presence in primary and secondary diagnosis of the ICD9 codes, during the first hospital admission. Hazard Ratio (adjusted by sex and age) were calculated using Cox regression analyses. <h3>Results</h3> There were a total of 338.343 hospital admissions in RA patients during the study period, accounting for a total of 186.491 patients (127.203 women (68,21%) and 59.288 men (31,79%). The mean number of hospital admissions was 1,81(SD 1,7), with a minimum of 1 and a maximum of 43. The median time of follow-up was 11,85 months (DE 27,4). There were a total of 18.641 exitus (5,5%). The HR (adjusted by sex and age) of the factors associated with hospital admissions mortality are shown in the next table: <h3>Conclusion</h3> In Spain, during the period of 1999-2015, the factors associated with hospital admission mortality (first admission) are: age, male sex, higher Charlson Index and longer hospital stay. The associated clinical variables are chronic hepatopathy, amyloidosis and neoplasm. Disclosure of Interests: None declared
Abstract 16348: Ecto-Nucleotidase-Derived Adenosine Promotes Mineralization Through A2a Receptor in Calcified Aortic Valves Disease
Authors: Maihemuti Abulajiang, Marie-Chloé Boulanger, Fayez Hadji, Rihab Bouchareb, Patrick Mathieu
Journal: Circulation (2014)

Background: Mineralization plays a crucial role in the development of calcific aortic valve disease (CAVD). The expression of ecto-nucleotidases may promote the mineralization of valve interstitial cells (VICs). We hypothesized that the expression of NPP1, which generates adenosine monophosphate (AMP), and 5’nucleotidase, an enzyme using AMP as a substrate to produce adenosine, may co-regulate the mineralization of the aortic valve. Methods: We have investigated the expression of NPP1 and 5’nucleotidase in CAVD tissues and determined the role of these ecto-nucleotidases on the mineralization of isolated VICs. The signaling pathway involving adenosine receptors was also studied. Results: In CAVD tissues, we documented that NPP1 and 5’nucleotidase enzyme activities were increased. NPP1 and 5’nucleotidase were co-expressed by VICs. In cell culture we found that mineralization induced by ATP was decreased by silencing NPP1 and 5’nucleotidase, suggesting a role for adenosine. Adenosine and specific A2a receptor agonist increased the calcification of VICs. Silencing of A2a receptor and the use of A2a-/- receptor mouse VICs abrogated adenosine-induced mineralization. Also, A2a receptor-mediated mineralization of VICs was negated by the transfection of a mutant dominant negative Gαs vector. Inhibition of the protein kinase A (PKA) pathway prevented adenosine-induced mineralization of VICs and expression of NPP1. We next showed that activation of PKA promoted in luciferase assay the activity of the NPP1 promoter. By using chromatin immunoprecipitation assay (ChIP) we documented that the cAMP response element binding protein (CREB), downstream of PKA, physically interacted with the NPP1 promoter region. Furthermore, the transfection of a mutant dominant active CREBDIEDML in isolated VICs increased the NPP1 promoter activity by 6.5-fold. Conclusion: The overexpression of NPP1 and 5’nucleotidase in CAVD promotes the mineralization of the aortic valve through A2a adenosine receptor, which signals through Gαs and the cAMP/PKA/CREB pathway. CREB is a positive regulator of NPP1 promoter activity in a positive feedback loop. The ecto-nucleotidases and/or A2a adenosine receptor could represent potential novel pharmaceutical targets in CAVD.
SAT0270 COMPREHENSIVE ICF CORE SET AND ICF-BASED QUESTIONNAIRE ASSESSING ACTIVITIES AND PARTICIPATION IN PATIENTS WITH SYSTEMIC SCLEROSIS: THE SCISCIF STUDY
Authors: Camille Daste, Agathe Papelard, Sophie Alami, Katherine Sanchez, Alexandra Roren, François Segretin, Marie-Martine Lefevre Colau, François Rannou, Luc Mouthon, Serge Poiraudeau, Christelle Nguyen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Recent guidelines regarding systemic sclerosis (SSc) emphasized the need of measuring functioning along with organ-specific measures, pointing out the importance of patient-reported outcome measures (1). The International Classification of Functioning, Disability and Health (ICF) endorsed by the WHO in 2001 set a unified language covering all dimensions of human functioning, including body structures, body functions, activities and participation and environmental factors. <h3>Objectives:</h3> To develop a comprehensive ICF core set for SSc and to conceive a patient-centered ICF-based questionnaire assessing activities and participation in patients with SSc. <h3>Methods:</h3> The development of the ICF comprehensive core set followed 2 steps (2). In the first step, meaningful concepts related to SSc were collected using data source triangulation from patients (N=18), experts (N=10) and literature (N=174 articles). In the second step, concepts were linked to the best-matching ICF categories by 2 independent reviewers according to prespecified linking rules (3). Finally, patient-reported activities and participation categories of the comprehensive ICF core set were translated into understandable questions <h3>Results:</h3> After linking concepts to ICF codes, 151 ICF categories were collected from focus groups, 22 from experts and 82 from literature. After fusion of the sources and removal of duplicates, the comprehensive ICF core set included 165 categories: 1 at the first level, 158 at the second level, 6 at the third level, with 50 categories on body functions, 15 on body structures, 53 on activities and participation and 47 on environmental factors. Patient-reported ICF categories on activities <h3>Conclusion:</h3> We developed a comprehensive ICF core set that offers a conceptual framework for SSc patients' care and health policy. Using a patient-centered approach, we conceived a patient-centered ICF-based questionnaire, the Cochin Scleroderma ICF-65 questionnaire, assessing activities and participation in patients with SSc. <h3>References</h3> [1] Merkel PA, Clements PJ, Reveille JD, Suarez-Almazor ME, Valentini G, Furst DE, et al. Current status of outcome measure development for clinical trials in systemic sclerosis. Report from OMERACT 6. J Rheumatol. 2003;30(7):1630-47. [2] Selb M, Escorpizo R, Kostanjsek N, Stucki G, Ustun B, Cieza A. A guide on how to develop an International Classification of Functioning, Disability and Health Core Set. Eur J Phys Rehabil Med. 2015;51(1):105-17. [3] Cieza A, Geyh S, Chatterji S, Kostanjsek N, Ustun B, Stucki G. ICF linking rules: an update based on lessons learned. J Rehabil Med. 2005;37(4):212-8. <h3>Disclosure of Interests:</h3> None declared
The evolutionarily mismatched nature of modern group makeup and the proposed application of such knowledge on promoting unity among members during times of intergroup conflict
Authors: Jiaqing O
Journal: Behavioral and Brain Sciences (2019)

Many modern-day groups differ from prehistoric ones regarding the proportion of members who are related to any particular individual. From an evolutionary mismatch lens, an appreciation of this disparity could help better explain the potential dilution of group cohesion during peacetime and inform novel, more effective approaches to enhancing group unity - strategies that might enhance national security around the globe.
PB1904 PROPHYLAXIS FOR OCCULT HBV INFECTION UNDER IBRUTINIB THERAPY: MANDATORY OR OPTIONAL?
Authors: A. Ercaliskan, A.E. Eskazan, A. Salihoglu, D. Keskin, D. Ozmen, T. Elverdi, M.C. Ar, T. Soysal
Journal: HemaSphere (2019)

Background: Ibrutinib is a Bruton's tyrosine kinase inhibitor which plays a critical role in the management of some B cell malignancies. Although there are some case reports and case studies indicating hepatitis B virus (HBV) reactivation under ibrutinib therapy in patients who were not given concomitant HBV prophylaxis, case studies showing contradictory results also exist (Blood. 2018.131(17):1987-9 and Leukemia&lymphoma. 2017.58(12):2966-8). Past or active HBV infection was an exclusion criteria for the clinical studies of ibrutinib. Aims: In this study, we wanted to present our single-center experience on the outcomes of patients with occult HBV infection receiving ibrutinib from a country with a relatively high incidence of HBV infection. Methods: Twenty-three patients with B cell malignancies receiving ibrutinib were evaluated retrospectively. Demographic features, previous treatments (including rituximab (RTX)) and follow-up durations, HBV infection and reactivation status, prophylaxis information, serum transaminase and total bilirubin levels were noted. Past HBV infection defined as concurrent detectable HBV core IgG Ab (Anti-HBc IgG) and undetectable HBV surface Ag (HbsAg). Active HBV infection defined as HbsAg and/or HBV core IgM Ab (Anti-HBc IgM) positivity. Quantitative HBV-DNA PCR results are also recorded, if available. Results: Of these 23 patients, twenty-two were eligable, and patients’ characteristics are displayed in Table 1. Median durations of ibrutinib therapy and entire follow-up were 9.5 and 96 months, respectively. All patients had received RTX prior to ibrutinib. 6 patients had past HBV infection, while 2 had active HBV infection. HBV prophylaxis was started with treatments prior to ibrutinib in 5 patients, whereas 3 patients with past HBV infection were not given prophylaxis. Among these 3 cases with Anti-HBc IgG positivity, two were also positive for HBV surface Ab (Anti-HBs). Currently, 2 of these 3 cases including the one who is Anti-HBs negative are both receving the 12th cycles, and the remaining one is at the 4th cycle of ibrutinib therapy. Serum Anti-HBs titers and liver function tests are being followed at 3-month intervals. To date, no signs of HBV reactivation was detected among our ibrutinib-treated patients.Summary/Conclusion: Although the number of patients is limited and follow-up periods are relatively short, our results indicate that patients with occult HBV infection treated with ibrutinib for B cell malignancies, might only be closely followed for HBV reactivation, rather than routine prophylactic anti-HBV treatment. Upfront prophylactic treatment might still be an option for patients who can not be followed regularly. Possibility of loss of Anti-HBs due to prior RTX exposure always should be kept in mind.
Prophylactic Use of Implantable Cardioverter-Defibrillators in the Prevention of Sudden Cardiac Death in Dialysis Patients
Authors: J. Wouter Jukema, Rohit J. Timal, Joris I. Rotmans, Liselotte C. R. Hensen, Maurits S. Buiten, Mihaly K. de Bie, Hein Putter, Aeilko H. Zwinderman, Lieselot van Erven, M. Jacqueline Krol-van Straaten, Nienke Hommes, Bas Gabreëls, Wim van Dorp, Bastiaan van Dam, Charles A. Herzog, Martin J. Schalij, Ton J. Rabelink
Journal: Circulation (2019)

Patients with end-stage renal disease who are undergoing dialysis are reported to be at high risk of sudden cardiac death (SCD), and to date, no therapy has been shown to be effective in reducing this risk. The feasibility and value of prophylactic implantable cardioverter-defibrillator (ICD) implantation to prevent SCD is uncertain.We conducted the ICD2 trial (Implantable Cardioverter-Defibrillator in Dialysis Patients), a prospective, randomized, controlled study investigating the value and safety of ICD implantation to prevent SCD in 200 patients on dialysis with a left ventricular ejection fraction ≥35%, after adequate screening and optimization of other treatments. The primary end point was SCD. Secondary end points were all-cause mortality and ICD-related complications.The trial was stopped as per the recommendation of the data and safety monitoring board for futility reasons after inclusion of 188 patients, 97 in the ICD group and 91 in the control group. The median duration of follow-up was 6.8 years (interquartile range, 3.8-8.8 years). SCD occurred in 19 of 188 cases (10.1%), 11 of 97 in the ICD group and 8 of 91 in the control group. The cumulative SCD incidence at 5 years was 9.7% (95% CI, 3.3%-16.2%) in the ICD group and 7.9% (95% CI, 1.7-14.0%) in the control group, resulting in a hazard ratio of 1.32 (95% CI, 0.53-3.29; P=0.55). Overall, 99 of 188 patients died (52.7%), 52 in the ICD group and 47 in the control group. Five-year survival probability was 50.6% (95% CI, 39.8%-61.5%) in the ICD group and 54.5% (95% CI, 43.0-66.0%) in the control group, resulting in a hazard ratio of 1.02 (95% CI, 0.69-1.52; P=0.92). Among 80 patients who received an ICD, 25 adverse events related to ICD implantation occurred.In a well-screened and well-treated population undergoing dialysis, prophylactic ICD therapy did not reduce the rate of SCD or all-cause mortality, which remained high.URL: http://www.controlled-trials.com . Unique identifier: ISRCTN20479861.
Hippocampal stem cells promotes synaptic resistance to the dysfunctional impact of amyloid beta oligomers via secreted exosomes
Authors: Maria-Adelaide Micci, Balaji Krishnan, Elizabeth Bishop, Wen-Ru Zhang, Jutatip Guptarak, Auston Grant, Olga Zolochevska, Batbayar Tumurbaatar, Whitney Franklin, Claudia Marino, Steven G. Widen, Arjun Luthra, Steven G. Kernie, Giulio Taglialatela
Journal: Molecular Neurodegeneration (2019)

Adult hippocampal neurogenesis plays an important role in synaptic plasticity and cogntive function. We reported that higher numbers of neural stem cells (NSC) in the hippocampus of cognitively-intact individuals with high Alzheimer's disease (AD) pathology (plaques and tangles) is associated with decreased synaptic amyloid beta oligomers (Aβο), an event linked to onset of dementia in AD. While these findings suggest a link between NSC and synaptic resistance to Aβο, the involved mechanism remains to be determined. With this goal in mind, here we investigated the ability of exosomes secreted from hippocampal NSC to promote synaptic resilience to Aβo.
Secondary prevention of gastric cancer: merging the endoscopic atrophic border with OLGA staging
Authors: Massimo Rugge, Diana Sacchi, David Y Graham, Robert M Genta
Journal: Gut (2019)

First, we wish to thank Dr Quach and his coauthors1 for their interest in our study. We are flattered by their statement that our numbers are 'quite convincing' and will attempt to mitigate their concerns.2 The authors are correct in that the eradication of Helicobacter pylori does not abolish all gastric cancer (GC) risk in patients with long-standing atrophic gastritis.3–5 This broad statement, however, requires some clarifications.
Response to Comment on Kim et al. The Effect of a Smartphone-Based, Patient-Centered Diabetes Care System in Patients With Type 2 Diabetes: A Randomized, Controlled Trial for 24 Weeks. Diabetes Care 2019;42:3–9
Authors: Eun Ky Kim, Young Min Cho
Journal: Diabetes Care (2019)

We thank Huo et al. (1) for their interest in our study (2) on the effect of a smartphone-based, patient-centered diabetes care system (mDiabetes) in patients with type 2 diabetes. In our study, the efficacy of mDiabetes was examined in the full analysis set, which excluded participants who failed to meet inclusion/exclusion criteria or lacked any postrandomization data to evaluate the effect of mDiabetes on glucose control. With respect to the comment, …
Immune-Active Microenvironment in Small Cell Carcinoma of the Ovary, Hypercalcemic Type: Rationale for Immune Checkpoint Blockade
Authors: Petar Jelinic, Jacob Ricca, Elke Van Oudenhove, Narciso Olvera, Taha Merghoub, Douglas A Levine, Dmitriy Zamarin
Journal: JNCI Journal of the National Cancer Institute (2017)

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a highly aggressive monogenic cancer driven by SMARCA4 mutations. Here, we report responses to anti-PD1 immunotherapy in four patients and characterize the immune landscape of SCCOHT tumors using quantitative immunofluorescence and gene expression profiling. Unexpectedly for a low mutation burden cancer, the majority of the tumors (eight of 11 cases) demonstrated PD-L1 expression with strong associated T-cell infiltration (R2 = 0.60–0.95). PD-L1 expression was detected in both tumor and stromal cells, with macrophages being the most abundant PD-L1-positive cells in some tumors (three of 11 cases). Transcriptional profiling revealed increased expression of genes related to Th1 and cytotoxic cell function in PD-L1-high tumors, suggesting that PD-L1 acts as a pathway of adaptive immune resistance in SCCOHT. These findings suggest that although SCCOHT are low–mutational burden tumors, their immunogenic microenvironment resembles the landscape of tumors that respond well to treatment with PD-1/PD-L1 blockade.