tbuckley/cabot-search huggingface dataset:
Abstract 12459: Downregulated Fli1 in Scleroderma Myeloid Cells May Contribute to Cardiac Fibrosis via a Galectin-3/mTOR Dependent Pathway
Authors: fatima el adili, Mortada Najem, Maria Trojanowska, Andreea M Bujor
Journal: Circulation (2021)

Introduction: Scleroderma (SSc) is an autoimmune fibrotic disease with high mortality and no effective therapies. Cardiac fibrosis in SSc is common and has a poor prognosis, but pathogenesis is unclear. Galectin-3 secretion by macrophages has been implicated in cardiac fibrosis, but its specific contribution to SSc cardiac disease has not been elucidated. We recently demonstrated that Fli1, a member of the Ets family of transcription factors, is decreased in SSc myeloid cells, and that Fli1 depleted macrophages have a profibrotic phenotype. We aim to evaluate the contribution of myeloid Fli1 to SSc cardiac fibrosis. Methods: Levels of galectin-3 were assessed by ELISA in serum, and qPCR and immunofluorescence in monocytes. Primary human cardiac fibroblasts were co-cultured with macrophages using inserts. Rapamycin (10nM) was used to treat the co-cultures. Western blot was used to assess protein levels of collagen and p70S6K. Collagen deposition in hearts from mice with conditional deletion of Fli1 in macrophages ( LysMCre/Fli1 fl/f l ) was assessed by picrosirius red. Results: SSc patients had higher expression of galectin-3 in monocytes and serum compared to healthy controls. Co-culture of human cardiac fibroblasts and Fli1 depleted macrophages resulted in induction of galectin-3 expression by macrophages, and activation of the mTOR/p70S6K pathway with enhanced collagen type I protein deposition by fibroblasts. These effects were blocked by the mTOR inhibitor Rapamycin, and by treatment of macrophages with siRNA against galectin-3. Deletion of Fli1 in macrophages via Cre-mediated recombination using LysMCre mice predisposed mice to develop cardiac fibrosis. Conclusions: These findings suggest that Fli1 deficiency in macrophages may contribute to SSc cardiac fibrosis, and that Rapamycin may be a potential therapeutic option for heart involvement in SSc.
Changes in the profile of newly HIV-diagnosed men who have sex with men, Madrid, 2014 to 2019
Authors: Oskar Ayerdi Aguirrebengoa, Mar Vera Garcia, Teresa Puerta López, Petunia Clavo Escribano, Juan Ballesteros Martín, Clara Lejarrag Cañas, Enrique Fuentes Ferrer, Montserrat Raposo Utrilla, Vicente Estrada Perez, Jorge Del Romero Guerrero, Carmen Rodríguez Martín
Journal: Eurosurveillance (2021)

Introduction Knowing the factors associated with HIV transmission is necessary in order to design preventive programmes tailored to the epidemiological situation in each region and population. Aim Our objective was to study the sociodemographic, clinical and behavioural characteristics of men who have sex with men (MSM) who were newly diagnosed with HIV infection. Methods We carried out an observational, descriptive, study on all MSM newly diagnosed with HIV infection in one clinic for sexually transmitted infections (STI) and HIV clinic in Madrid between 2014 and 2019. Information on sociodemographic, clinical, and behavioural characteristics of participants per year of diagnosis was collected. Results We detected a total of 1,398 people with HIV infection, 253 of whom were recent seroconverters (rSCV) with a median duration of documented seroconversion of 6 months. From the total, 97.9% infections were sexually transmitted and 2.1% involved injected drugs, i.e. slam practices. The average age was 32.9 years (range: 15.6–74.9), 51.8% were Spanish and 40% Latin American. These diagnoses decreased in Spanish people and increased in Latin Americans during the study period. Of the rSCV, 73.9% had condomless sex under the influence of drugs and 28.9% participated in chemsex sessions. Apps were used by 92.6% rSCV for sexual encounters and 70.4% of them attributed HIV transmission to their use. Conclusions Combination of HIV prevention strategies, as pre-exposure prophylaxis, should be reinforced among young MSM, especially those born in Latin America, those who use drugs for sex, and those who use apps in search of sexual contacts.
Long-Term Outcome of Peripheral Blood Autologous Stem Cell Transplantation (AutoSCT) for De Novo Acute Myeloid Leukemia in Patients Achieving First Complete Remission after One Vs Two Induction Courses: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
Authors: Arnon Nagler, Jacques-Emmanuel Galimard, Myriam Labopin, Didier Blaise, William Arcese, Depei Wu, Gwendolyn Van Gorkom, Marie Thérèse Rubio, Tobias Gedde-Dahl, Anne Huynh, Francesco Lanza, Norbert Claude Gorin, Mohamad Mohty, Silvia Maria Trisolini, Arnaud Pigneux
Journal: Blood (2021)
Abstract 10564: Inverse Association Between Serum Albumin Levels and Myocardial Extracellular Volume in Patients with Severe Aortic Stenosis
Authors: Arthur Shiyovich, Ygal Plakht, Yoav Hammer, Yaron Aviv, Maya Wiessman, Gideon Shafir, Hanna Vaknin-Assa, Ran Kornowski, Ashraf Hamdan
Journal: Circulation (2021)

Introduction: Severe aortic stenosis (AS) is often characterized by myocardial interstitial fibrosis (MIF). MIF, classically measured by magnetic resonance imaging, was shown to be accurately measured by computed tomography (CT)-derived extra cellular volume fraction (ECVF). Serum albumin level (SA, g/dL) has been shown to correlate with ECVF among patients with heart failure preserved ejection fraction. Aim: To evaluate the association between SA and ECVF among patients with severe symptomatic AS. Methods: Patients with symptomatic severe AS who were evaluated as candidates for intervention between 2016 and 2018, were enrolled prospectively. All patients underwent pre- and post-contrast CT for estimating myocardial ECVF. Valid ambulatory SA within 6 weeks of the cardiac CT were obtained and classified as (tertials): &lt;3.8, (3.8-4.19), ≥4.2 g/dL. Patients with acute systemic illness at the time of the albumin test were exclude. Results: The study included 68 patients, mean age 80.94±6.5, 53% females. Patients with lower SA were more likely to have chronic renal failure, prior percutaneous coronary interventions (PCI) and a reduced functional class. The mean ECVF (%) in the study cohort was 40.96±11.6%, significantly higher among the patients in the lower SA level groups (50±11.6% vs. 38.2±7.3% vs. 32.8±8.6% in the &lt;3.8 g/dL, 3.8-4.19 g/dL, ≥4.2 g/dL groups respectively, p for trend&lt;0.001). A statistically significant inverse correlation (figure 1) was found between SA levels and ECVF (r=-0.7, p&lt;0.001). Multivariable analysis showed significant independent association between low SA and ECVF. Conclusions: SA level is inversely associated with CT-derived ECVF in patients with severe AS. Additional studies are warranted to elucidate the pathophysiological mechanisms explaining the observed association and potential clinical implications
Abstract 11484: Subclinical Renal Impairment and Inflammation in Cognitive Frailty in Older Adults (Tanushimaru Cohort Study)
Authors: Nagisa Morikawa, Hisashi Adachi, Mika Enomoto, Ako Fukami, Akiko Sakaue, Yamamoto Maki, Hiromi Sato, Yoshihiro Fukumoto
Journal: Circulation (2021)

Introduction: Sarcopenia or slow gait speed (SGS) strongly interact with cognitive impairment (CI), that is cognitive frailty, possibly because of reinforcing common underlying pathophysiologies. We previously reported that renal impairment (RI) was associated with CI and inflammation is said to be important in the association. Associations of RI and inflammation with cognitive frailty has been understudied. Hypothesis: RI and inflammation are associated with cognitive frailty. Methods: We conducted a cross-sectional study in 1368 population-based sample (mean age: 68.7±11.3 years, men:40.5%) of Tanushimaru, Japan in 2018. We measured urinary albumin-creatinine ratio (ACR) and high-sensitivity C-reactive protein (hsCRP) and assessed cognitive function by Mini-Mental State Examination (MMSE) and 5m walking time. RI was defined as ACR ≧30mg/dL and inflammation was defined as higher than median log-hsCRP. MMSE scores ≦27 out of 30-points was classified as CI and SGS was defined as &lt;1m/s. Multivariable logistic regression analyses were performed to examine an association of RI and inflammation with CI and SGS. Results: Prevalence of CI and SGS were 29.3% and 44.3%, respectively. SGS was more prevalent in participants with CI than those with normal cognition (64.4% vs 35.7%, p&lt;0.0001). 15% of participants had RI and they had higher serum hsCRP than those with normal renal function (0.067mg/dL vs 0.047mg/dL, p&lt;0.0001). Higher log-ACR was significantly associated with CI and SGS, while higher log-hsCRP was associated with only SGS. Age, sex-adjusted odds ratio (OR) of RI was 1.85 (95% confidence interval (CI): 1.19-2.87) in the group with CI and SGS compared to the group with normal cognition and gait speed, while OR of inflammation was 1.52 (95%CI: 1.10-2.10) in the group with CI and SGS. (Fig 1). Conclusions: RI and inflammation were associated with cognitive frailty, especially inflammation was strongly associated with frailty.
Abstract 356: Angiotensin II as a Paracrine Factor in Heart Environment
Authors: Isabela C Pereira, Maria Laura P Rodrigues, Lívia G Teodoro, Fabiano F Vieira, Roseli A Gomes
Journal: Circulation Research (2015)

Besides its potent vasoconstrictor action, the Angiotensin II (Ang II) has other important biological roles as autocrine and paracrine actions, being fundamental in cardiovascular homeostasis. Changes in the levels of this substance in the pericardial fluid (PF) are associated with the development of cardiovascular diseases. The aim of this study was to evaluate the presence of members of the classical and alternative pathways of the Renin Angiotensin System (RAS), as well as one of its main effectors peptides, Ang II, in PF of patients with coronary artery disease and assess the role of Ang II as a factor able to promote the process of epithelial-mesenchymal transition epicardial mesothelial cells in genetically modified mice. Male and female patients with coronary artery disease and controls patients were involved in this study. The ELISA’s results showed significant amounts of Ang II, Angiotensin Converting Enzyme (ACE) and chymase in PF coronary artery disease male patients. Chymase positive mast cells were identified by immunohistochemical and quantitative analysis demonstrated a greater density of mast cells in this group. Expression of AT1 and AT2 was detected by immunohistochemistry in patients of male and female groups with coronary artery disease and controls. The scaling of the parietal mesothelium is a process seen in all groups, although when quantified showed no significant differences between them. Ang II was not able to increase the epithelial-mesenchymal transition of the epicardial cells in infarcted mice genetically modified. The presence of constituents of the classical and alternative pathways of RAS in the PF suggest an important role for this fluid as a modulator of cardiac functions. Specifically in relation to Ang II, their biological roles in the cardiovascular system still need to be further investigated. The identification in the cardiovascular microenvironment of paracrine factors and your action mechanisms, which stimulate and promote cardiac repair, may allow a better understanding of heart disease and the development of new therapies.
Abstract 12825: Immediate versus Staged Complete Revascularization in Acute ST-segment Elevation Myocardial Infarction Patients With Multi-Vessel Disease Undergoing Primary Percutaneous Coronary Intervention: Prospective, Randomized, Multicenter Trial of Complete versus Culprit Lesion Revascularization in Acute ST-segment Elevation Myocardial Infarction Patients With Multivessel Disease Undergoing Primary Percutaneous Coronary Intervention With Everolimus Eluting Stent (cocua Trial)
Authors: Soohyung Park, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Jinah Cha, Kyuho Lee, Seungmin Back, Jieun Lee, Dong O Kang, Ji Bak Kim, Jah Choi, Seung-young Roh, Jin O Na, Cheol Ung Choi, Eung Ju Kim, Chang Gyu Park, Hong-Seog Seo, Seung Woon W Rha
Journal: Circulation (2021)

Background: In the present study, we aimed to compare the 12-month clinical outcomes of immediate versus staged complete revascularization in acute ST-segment elevation myocardial infarction (STEMI) patients with multivessel disease undergoing primary percutaneous coronary intervention (PCI) with everolimus-eluting stents (EES). Method: A total of 248 patients were enrolled in a prospective, randomized, open-label, multicenter registry. Immediate complete revascularization was defined as simultaneous PCI of the culprit and non-culprit lesions during the index procedure (Immediate group). Staged complete revascularization was defined as PCI of non-culprit lesion as a separate staged procedure after the culprit lesion PCI (mean 4.4 days, interquartile range; 1 to 11.4, Staged group). The study end points were major adverse cardiovascular events (MACE; the composite of total death, recurrent myocardial infarction, and revascularization), and individual hard endpoints including cardiac death, stent thrombosis and stroke at 12 months clinical follow up. Results: Although the incidence of MACE was not significantly different between the two groups (11.6% vs. 7.5%, p = 0.313), the incidence of total death was higher in the immediate group than the staged group (9.7% vs. 2.8%, P=0.040). Despite the incidence of target lesion and vessel revascularization were similar, there was a trend toward higher incidence of TLR- MACE in the immediate group than the staged group (9.7% vs. 3.7%, p =0.086). There was no significant difference in the risk of in-hospital complications including transfusion, bleeding, acute renal failure or acute heart failure between the groups. Conclusion: For STEMI patients with multi-vessel disease undergoing primary PCI with drug-eluting stents, routine immediate complete revascularization should not be justified possibly due to higher event risks.
Clinical Profile, Complications and Outcomes of Patients with Acute Promyelocytic Leukemia: Indian Perspective
Authors: Tejasvini Vaid, Mukul Aggarwal, Pradeep Kumar, Rishi Dhawan, Jasmita Dass, Ganesh Viswanathan, Tulika Seth, Seema Tyagi, Manoranjan Mahapatra
Journal: Blood (2021)
“It's been up and down”—perspectives on living through COVID-19 for individuals who experience homelessness: a qualitative study
Authors: Emma A Adams, Jeff Parker, Tony Jablonski, Joanne Kennedy, Desmond Hunter, Fiona Tasker, Claire Smiles, Cassey Muir, Emily Widnall, Kate Dotsikas, Chris Reed, Martin Burrows, Amy O'Donnell, Eileen Kaner, Sheena E Ramsay
Journal: The Lancet (2021)
Abstract 12166: Biomechanical Impact of Valve Sparing Procedure Onto the Native Aorta, a Multi-Patient in silico Study
Authors: Valentina Scarponi, Alessandro Caimi, Simone Saitta, maria chiara palumbo, Leonard N Girardi, Mario F Gaudino, Mary J Roman, Jiwon Kim, Jonathan W Weinsaft, alberto redaelli
Journal: Circulation (2021)

Introduction: Ascending thoracic aortic aneurysms (TAA) provide a nidus for dissection, which can be prevented by surgical prosthetic graft replacement. Grafts eliminate risk in resected regions, but are stiffer than native aortic tissue and can thus alter downstream hemodynamics. This study used computational modeling of fluid structure interaction (FSI) to study biomechanical impact of proximal aortic graft replacement on the descending aorta. Methods: TAA pts undergoing cardiac MRI (CMR) prior to and after valve sparing proximal aortic graft replacement (VSR) surgery were studied via FSI. Patient-specific anatomy was reconstructed by segmentation of 3D MR angiography. 4D flow was used to prescribe velocity at the inlet of the model and to define three-elements Windkessel parameters used to impose outlet boundary conditions. Results: FSI models were constructed in 5 male patients (61±10.6 years old) who underwent CMR pre (1.7±1.5 weeks) and post (28.5±2.3 weeks) proximal aortic graft replacement. Qualitative and quantitative comparison of numerical results with 4D-flow data confirmed FSI model’s ability to reproduce patients’ fluid-dynamics (mean RRMSE 0.244±0.059). Regarding post-operative hemodynamics, a post-operative oscillatory shear index (OSI) increment (Pt1: p-value &lt; 0.05) and systolic peak wall shear stress (WSS) variation (Pt1: p-value &lt;0.001, Pt3: &lt;0.01, Pt5: &lt;0.0001) were observed, particularly in proximal descending aorta ( Fig 1 ). Furthermore, from 9 to 63% post-operative distensibility increment was detected. Finally, a mean 4% principal strain intensification was noticed at graft’s suture site if compared to the native portion of the ascending aorta ( Fig 1 ). Conclusion: Computational FSI modeling analysis demonstrates VSR technique to alter downstream biomechanics, including wall shear stress variation and increased strain immediately distal to grafted territories.
Determining the Rate of Anti-PF4 Antibody Positive Results in Patients Presenting with Venous Thrombosis but a Normal Platelet Count Following ChAdOx1 Ncov-19 Astrazeneca Vaccination: An Australian Combined State Testing Centre Experience
Authors: Emma J Leitinger, Joanne Clifford, Michael Parker, Amanda Iacobelli, Pauline Sung, Vivien Chen, Timothy A. Brighton, Christine Shu Mei Lee, Lisa Clarke, Erica Malan, Geoffrey Kershaw, Noor Shadood, Freda H. Passam, Emmanuel J Favaloro, Huyen A Tran, Sanjeev D Chunilal
Journal: Blood (2021)
Abstract 10814: Prolongation of the Refractory Period is a Key Mechanism of Optogenetic Termination of Atrial Fibrillation in Mouse Hearts
Authors: Motoki Nakao, Masaya Watanabe, Hiroyuki Natsui, Takuya Koizumi, Takahide Kadosaka, Taro Koya, Hikaru Hagiwara, Rui Kamada, Taro Temma, Toshihisa Anzai
Journal: Circulation (2021)

Backgrounds: Optogenetics is a new technique that employs light-sensitive channels and manipulates the cell membrane potential. Although painless defibrillation of reentry arrhythmias such as atrial fibrillation (AF) using optogenetics has been reported, the mechanism has not been fully elucidated because of the difficulty to evaluate the action potential (AP) modification by in/ex-vivo light illumination. Purpose: Our aim is to clarify the mechanism of optogenetic defibrillation of AF in a mouse heart by voltage-sensitive optical mapping. For this purpose, we employed a novel approach using brief light illumination combined with a systematic electrical stimulation protocol. Methods and Results: Hearts from transgenic mice expressing channelrhodopsin-2 in atrial cardiomyocytes were explanted and perfused with tyrode’s solution containing low K + concentration (2.7mM) and K ACh -channel activator carbachol (2μM). Atrial tachyarrhythmia induced by burst pacing was terminated by blue light (470nm) illumination with a pulse duration of 10 ms and a light intensity of 16 mW/mm 2 with a probability of 64.7 ± 8.1% (n=9). The termination rate depended on the pulse duration and light intensity. Then, we examined whether brief light illumination (10 ms, 6mW/mm 2 ) at different time phases from the rise of the AP (phase 0) to the repolarization (phase 4) modify AP shape and prolong the effective refractory period (ERP) using voltage-sensitive optical mapping. Brief light illumination prolonged AP duration and ERP in all time phases. The degree of ERP prolongation was dependent on the pulse duration, but not on the light intensity above 1 mW/mm 2 . Finally, we measured the attenuation of blue light intensity through the atrial tissue and observed that the intensity decreased by 38.1 ± 3.5% at 10mW/mm 2 on 3 mm 2 circular area(n=6), suggesting that high-intensity light also modulates the APs of atrial cardiomyocytes in deeper layers. Conclusion: Our results directly demonstrated that brief light illumination prolonged the atrial refractory period depending on pulse duration in a perfused heart and suggests the prolongation of the refractory period is a key mechanism of optogenetic termination of AF.
IMMU-21. DIFFERENTIAL EXPRESSION OF ADHESION MOLECULES DEFINES MYELOID CELL INFILTRATION IN GLIOBLASTOMA AND COMPRISES A THERAPEUTIC TARGET
Authors: Defne Bayik, Cynthia Bartels, Katreya Lovrenert, Dionysios Watson, Kristen Kay, Adam Lauko, Peter Scacheri, Justin Lathia
Journal: Neuro-Oncology (2021)

Abstract A potently immunosuppressive tumor microenvironment facilitates progression of glioblastoma (GBM). Immunotherapies have had variable success in improving the outcome of GBM patients, suggesting that there is a need to gain insight into the mechanisms of immunosuppression. Myeloid-derived suppressor cells (MDSCs) associate with poor prognosis and treatment resistance of GBM patients, but the distinct role of individual populations is not well-defined. We previous showed that monocytic MDSCs (mMDSCs) accumulated in tumors of mice and patients, while granulocytic MDSCs (gMDSCs) mainly remained in the circulation. Furthermore, nonspecific targeting of mMDSCs with chemotherapies provided therapeutic benefit in preclinical models of GBM, suggesting that mMDSCs drive disease progression. To investigate the differential function of mMDSCs versus gMDSCs in GBM, we adoptively transferred bone marrow-derived MDSC subsets into tumor-bearing mice. Mice that received mMDSCs succumbed to disease sooner compared to control mice, which was not observed with gMDSC transfer. To determine the basis of this pro-tumorigenic activity of mMDSCs, we performed ATAC-sequencing and comparison of differentially accessible regions indicated that cell adhesion pathways were significantly upregulated in mMDSCs. Aligned with this epigenetic profile, mMDSCs from bone marrow and blood had significantly higher surface integrin β1 and integrin β7 expression compared to gMDSCs. To evaluate the role of integrins in MDSC behavior, we pre-treated mMDSCs with anti-integrin β1 prior to adoptive transfer. Blockade of integrin β1 interfered with the pro-tumorigenic role of mMDSCs compared to isotype controls. Similarly, blockade of integrin β1 and integrin β7 systemically extended the survival duration of tumor-bearing mice. Finally, high expression of integrin β1 and integrin β7 served as a poor prognostic indicator in GBM patients. Our findings indicate that modulation of immunosuppressive myeloid cells by leveraging differences in adhesion mechanisms represents a potential immunotherapeutic option for GBM.