tbuckley/cabot-search huggingface dataset:
Abstract 268: Combined Use of VA-ECMOecmo and Impella (ECPELLA) Improves Outcome of Patients with Out of Hospital Cardiac Arrest or Cardiac Arrest at the Emergency Room
Authors: Yudai Tamura, Takashi Unoki, Tomoko Nakayama, Motoko Kametani, Daisuke Takagi, Yutaka Konami, Hiroto Suzuyama, Masayuki Inoue, Tetsuo Yufu, Kazuhisa Kodama, Megumi Yamamuro, Eiji Taguchi, Tadashi Sawamura, Koichi Nakao, Tomohiro Sakamoto
Journal: Circulation (2020)

Background: Extracorporeal CPR (E-CPR) is a lifesaving method for refractory cardiac arrest (CA), and IABP has been often used as the additional circulatory support. However, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) increase damaged left ventricular (LV) afterload. The percutaneous microaxial pump, IMPELLA, can reduce damaged LV preload and afterload with circulatory support. Concomitant use of VA-ECMO and IMPELLA (ECPELLA) may have significant effect on clinical outcome. Objective: This study is to evaluate the effects of ECPELLA on clinical outcome of patients with out of hospital cardiac arrest (OHCA) or CA at the emergency room (ERCA) who underwent E-CPR. Method: We retrospectively reviewed 140 consecutive patients who underwent E-CPR from January 2012 through May 2020 in our institute. Seventy-four in-hospital CA patients were excluded, and 66 patients with OHCA or ERCA were recruited. Patients were divided into three groups ECEPLLA (n=13), ECMO with IABP (n=40), and ECMO alone (n=13). The primary endpoint was 30-day mortality. Secondary endpoint was good neurological outcome at hospital discharge defined as cerebral performance categories (CPC) of 1 or 2. Result: There were no significant differences in age, sex, OHCA, acute coronary syndrome in all three groups. The rate of shockable rhythm was higher in the ECPELLA and ECMO with IABP groups than ECMO alone. ECPELLA had the shortest time from CA to ECMO support compared with other groups. The 30-day survival and favorable neurological prognosis rates were significantly higher in the ECPELLA group, compared with other groups (ECPELLA: 61% vs. IABP: 18% vs. ECMO alone: 15%; P=0.008, ECPELLA: 38% vs. IABP: 8% vs. ECMO alone: 8%; P=0.03). Multivariate cox regression analysis including age, sex, time from CA to ECMO support and ECPELLA revealed that age (hazard ratio [HR], 1.36 (10 years increase), 95% confidence interval [CI], 1.11-1.67, P=0.04), male (HR, 2.42, 95%CI, 1.04-5.66, P=0.04), time from CA to ECMO support (HR, 1.01, 95%CI, 1.01-1.03, P=0.04), and ECPELLA (HR, 0.35, 95%CI, 0.13-0.91, P=0.03) were significantly associated with 30-day mortality. Conclusion: ECPELLA could improve 30-day mortality and neurological outcome in OHCA or ERCA patients who underwent E-CPR.
Abstract 15925: Efficacy and Safety of Pulmonary Vein Isolation in Active Duty Military Members With Atrial Fibrillation
Authors: Andrew S Wilson, Kelvin N Bush
Journal: Circulation (2020)

Introduction: The efficacy and safety of pulmonary vein isolation (PVI) for atrial fibrillation (AF) in the active duty (AD) military population has not been previously reported. Hypothesis: We postulate that PVI is an efficacious and safe treatment for young AD service members with AF. Methods: AD military personnel with AF who underwent PVI from 2004 to 2019 were retrospectively analyzed in four age groups (group 1, n=26, 18 to 27 years; group 2, n=38, 28 to 37 years; group 3, n=28, 38 to 49 years; group 4, n=12, ≥50 years). Primary endpoints were (1) PVI procedural efficacy defined as no or rare AF recurrence (&lt;6 episodes) 12 months after last PVI with or without antiarrhythmic drugs (AAD) and (2) procedure-related adverse events and complications. Results: 104 personnel (mean age 35.6+9 years, 84.6% paroxysmal AF, mean LVEF 60.2+6%, 19.2% maintained on AAD after PVI) underwent 142 PVI procedures with a mean follow up of 55.8+47 months. Procedural efficacy was attained in 96.2% of group 1, 78.9% of group 2, 75.0% of group 3, and 66.7% of group 4 (P=0.004, Figure 1). Freedom from AF was reached in 80.3% of group 1, 55.3% of group 2, 46.4% of group 3, 41.7% of group 4 (P=0.02). AADs were maintained in 11.5% of group 1, 21.0% of group 2, 14.3% of group 3, 41.7% of group 4 (P=0.144) and there was no difference in AF recurrence rates between those with AADs and those without (P=0.091). LVEF &lt;50% trended towards being a significant predictor of AF recurrence (OR, 7; 95% CI, 0.75-65; P=0.051). Complications occurred in only 4 (3.8%) cases (pulmonary vein stenosis, cardiac tamponade, arteriovenous fistula) with no complications in the youngest group. Conclusions: This study suggests that PVI is an effective and safe therapy for younger military personnel with AF desiring to decrease their individual AF burden.
IL-6 trans-signaling promotes the expansion and anti-tumor activity of CAR T cells
Authors: Zhiwu Jiang, Rui Liao, Jiang Lv, Shanglin Li, Diwei Zheng, Le Qin, Di Wu, Suimin Chen, Youguo Long, Qiting Wu, Suna Wang, Simiao Lin, Xiaohan Huang, Zhaoyang Tang, Pengcheng Shi, Hongsheng Zhou, Qifa Liu, Ruocong Zhao, Yangqiu Li, Yang Jie, Wei Wei, Peilong Lai, Xin Du, Shuzhong Cui, Robert Weinkove, Pentao Liu, Duanqing Pei, Yao Yao, Peng Li
Journal: Leukemia (2020)
Abstract 13212: Cardiovascular Benefits of Apabetalone: A Meta-analysis
Authors: Hang Long Li, Qi Feng, Yue Fei, bernard cheung
Journal: Circulation (2020)

Introduction: Apabetalone is a novel drug that reduces inflammation and thrombosis by inhibiting bromodomain and extra-terminal proteins (BET). Three phase II trials suggested benefits whereas the recent phase III BETonMACE trial did not. To reconcile these differences, we performed a meta-analysis of all trials on apabetalone. Methods: MEDLINE, EMBASE, Cochrane Library, and ClinialTrials.gov were searched for randomized controlled trials of apabetalone up to May 05, 2020. The outcomes of interest were major adverse cardiovascular events (MACE) and hospitalization for heart failure. The secondary outcomes were death, myocardial infarction (MI), coronary revascularization, high-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I). Pooled risk ratios (RRs) or mean differences (MD) in a fixed-effects model were generated using the “ meta ” package in R (version 3.6.3). Results: Four trials (median follow-up 3-26.5 months) with altogether 3223 patients were included. All patients had coronary artery disease and received standard statin therapy. Apabetalone significantly reduced MACE (RR 0.78, 95% CI: 0.63-0.96) and hospitalization for heart failure (RR 0.48, 95% CI: 0.33-0.70) compared to placebo (Fig.). No significant differences were observed for death (RR 0.87, 95% CI: 0.63-1.21), MI (RR 0.82, 95% CI: 0.62-1.10), or coronary revascularization (RR 0.67, 95% CI: 0.31-1.49). Apabetalone increased ApoA-I (MD 2.82%, 95% CI: 1.36-4.28) and HDL (MD 0.04%, 95% CI: 0.02-0.07). Conclusions: Although the BETonMACE trial failed to demonstrate significant benefits, our meta-analysis shows that apabetalone reduces MACE and hospitalization for heart failure in patients with coronary artery disease. Larger outcome trials are urgently needed to investigate the benefits of epigenetic modulation through BET protein inhibition.
Radiology services should become more patient centred, says report
Authors: Jacqui Wise
Journal: BMJ (2020)

Improving patient experience should be at the centre of work to increase capacity in radiology services, according to a report from the Getting It Right First Time (GIRFT) programme.1

The NHS carries out almost 120 000 radiological procedures in England daily and the number is increasing by 1.3m annually. Almost all trusts need more staff to meet this demand and there is huge pressure on equipment and an urgent need for more physical space in many radiology services, the report said.

The comprehensive report, based on visits to more than 150 hospital units in England, found that radiology teams are “providing a high quality service in …
Abstract 12726: Crucial Role of <i>Jak2</i> V617f-positive Myeloproliferative Neoplasm in the Development of Aortic Aneurysm
Authors: Tetsuro Yokokawa, Tomofumi Misaka, Yusuke KIMISHIMA, Kento Wada, Keiji Minakawa, Koichi Sugimoto, Takafumi Ishida, Kazuhiko Ikeda, Yasuchika Takeishi
Journal: Circulation (2020)

Objective: To investigate the impact of hematopoietic JAK2V617F, which causes myeloproliferative neoplasms (MPNs), on the development of aortic aneurysm (AA). Approach and Results: We applied a bone marrow transplantation (BMT) strategy using the donor cells from Jak2 V617F transgenic (JAK2 V617F ) mice into the lethally irradiated apolipoprotein E-deficient mice. To induce the AA formation and progression, the recipient mice (BMT mice) were subjected to continuous angiotensin II infusion. Abdominal aortic diameter in JAK2 V617F -BMT mice was significantly enlarged compared to the control wild-type (WT)-BMT mice in response to angiotensin II. The incidence of abdominal AA was significantly higher in JAK2 V617F -BMT mice than in WT-BMT mice. Hematopoietic JAK2V617F accelerated aortic elastic lamina degradation as well as activation of matrix metalloproteinase (MMP)-2 and MMP-9 in the abdominal aorta. The numbers of CD68 + macrophages and Ly6B.2 + neutrophils and cytokine expressions such as Ccl6 and Tgfb1 were significantly increased in the abdominal aorta of JAK2 V617F -BMT mice accompanied by STAT3 activation. Bone marrow-derived macrophages carrying JAK2V617F showed elevations of both Mmp2 and Mmp9 mRNA expression. Finally, we found that 23% of MPN patients with JAK2 V617F mutation showed the presence of AA and increases in TGFB3 and IL-8 mRNA expression of the peripheral leukocytes. Conclusions: Hematopoietic JAK2V617F was involved in the development of AA through increases in the infiltration of inflammatory cells and MMP activation. Our findings provide a novel feature of vascular complication of AA in MPNs due to constitutive activation of the hematopoietic JAK-STAT pathway.
Abstract 17234: Elevated Atherosclerotic Biomarkers in Mice With Mild Blast Traumatic Brain Injury and Chronic Variable Stress
Authors: Maureen N Hood, Vincent B Ho, Nisha Plavelil, Tao-Yiao Wu, Michaelson Luke, Mario Oyola
Journal: Circulation (2020)

Introduction: Traumatic brain injury (TBI) and stress are significant health concerns that have atherosclerotic cardiovascular disease (ASCVD) effects. Stress and injury can elevate neurochemicals and hormones in the brain that lead to dysfunction of the hypothalamic-pituitary-adrenal axis and the autonomic nervous system increasing inflammation, which plays a role in the development of ASCVD. Animal models can provide a method of separating mild TBI (mTBI) from models of chronic stress. Hypothesis: We hypothesize that mild blast TBI (mbTBI) and chronic variable stress (CVS) will result in elevated ASCVD biomarkers in mice. Methods: Frozen hearts from C57BL/6J mice (8 weeks, N=16, 8 male/8 randomly cycling female) were obtained through an IACUC approved study. The C57BL/6J mice were part of a mild blast TBI (mbTBI) study utilizing a blast chamber to receive a short duration shock wave (&lt;10 msec, mean peak pressure of blast waves 19.9 psi). A group was subjected to CVS for two weeks prior to the blast, plus one week after blast. All groups were followed for four weeks. Western Blots with relative expression (normalized) were performed using an infrared imaging system. ERK1, ERK2, Galactein 3, Endothelin-1, BDNF, NT-Pro-BNP, and NRG1. ANOVA with Tukey HSD correction and descriptive statistics were performed using SPSS with significance by α of 0.05. Results: ERK1: mbTBI and CVS (p&lt;0.05). CVS +mbTBI to CVS (0.015)( p&lt;0.05 ), compared to mbTBI (0.017). ERK2: mbTBI sham = 0.009, CVS only = 0.008, mbTBI only = 0.008 and CVS + mbTBI = 0.012. Galectin-3 (Gal-3): CVS only = 0.144, CVS+mbTBI = 0.168, mbTBI (0.114) to sham (0.111) ( p&lt;0.05 ). NT-Pro-BNP: CVS+mbTBI = 0.168, sham 0.076. mbTBI alone (0.077) and CVS alone (0.078). NRG1: mbTBI (0.195) and mbTBI with CVS (0.178). CVS only group (0.157). ET-1: mbTBI sham = 0.068, CVS only = 0.080 mbTBI only = 0.084 and CVS+mbTBI = 0.134. BDNF: CVS only = 0.053, CVS+mbTBI = 0.069. Sham group (0.047), mbTBI (0.038). Conclusion: Our results on proteins related to a broad spectrum of vascular growth, innervation, function, inflammation and markers of atherosclerotic plaque development suggest that mbTBI and/or chronic stress may increase risk for developing early ASCVD.
Antimicrobial resistant infections keep rising despite fall in GP prescriptions
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Antimicrobial resistant infections in England increased from 61 946 in 2018 to 65 162 in 2019—equivalent to 178 infections a day—despite antibiotic consumption continuing to fall.

The total consumption of antibiotics last year fell to 17.9 defined daily doses per 1000 people per day in 2019, compared with 19.4 in 2015, according to the English Surveillance Programme for Antimicrobial Utilisation and Resistance.1

This was mainly because of a sustained reduction (12.2% between 2015 and 2019) in antibiotics …
Biomarkers for Prostate Cancer
Authors: Danil V. Makarov, Stacy Loeb, Robert H. Getzenberg, Alan W. Partin
Journal: Annual Review of Medicine (2008)

The development of biomarkers for prostate cancer screening, detection, and prognostication has revolutionized the management of this disease. Prostate-specific antigen (PSA) is a useful, though not specific, biomarker for detecting prostate cancer. We review the literature on prostate cancer biomarkers, including serum markers (PAP, tPSA, fPSA, proPSA, PSAD, PSAV, PSADT, EPCA, and EPCA-2), tissue markers (AMACR, methylated GSTP1, and the TMPRSS2-ETS gene rearrangement), and a urine marker (DD3PCA3/UPM-3). Future research should focus on validation of already existing biomarkers and the discovery of new markers to identify men with aggressive prostate cancer.
Abstract 13606: Cardiac Fibroblast Derived Matrix-educated Macrophages Express VEGF and IL-6, and Recruit Mesenchymal Stromal Cells
Authors: Sushmita Roy, Keith Spinali, Eric G Schmuck, John Kink, Peiman Hematti, Amish N Raval
Journal: Circulation (2020)

Introduction: Polarizing monocytes into macrophages that possess anti-inflammatory and angiogenic properties could be cardio-reparative following myocardial infarction. Co-culturing cardiac fibroblasts (CF) with monocytes is observed to lead to alternatively activated macrophages. We previously showed that CF produce a unique cardiac matrix (CX) that is fibronectin enriched. Whether decellularized CX can drive differentiation of monocytes to macrophages with angiogenic and anti-inflammatory properties is unknown. Hypotheses: (i) CX educated macrophages (CXMq) that secrete VEGF and IL-6, which have known angiogenic and anti-inflammatory properties respectively, (ii) CXMq can recruit mesenchymal stromal cells (MSC), which have known anti-inflammatory properties and (iii) fibronectin is responsible for this effect. Methods: Human monocytes (CD14 + ) were cultured on CX, plastic and gelatin. After 3 days, flow expression of the macrophage markers CD14, CD16, CD163, CD206, PDL1, CD86, and HLA-DR was measured. VEGF and IL-6 levels were measured from the spent media. A transwell migration assay was performed by placing monocytes on CX in the lower chamber and MSC in the upper chamber. CX was enzymatically dispersed and flow cytometry was performed for CD14 (macrophage marker) and CD73 (MSC marker). Migration was defined as the % of MSCs reaching the lower chamber (see Figure). Controls included monocytes plated on plastic, and monocyte/CX combination cultured with and without fibronectin integrin receptor inhibitor. Results: CXMq secreted high levels of VEGF and IL-6 and also had low expression of inflammatory markers CD16, CD86, HLADR. Further, CXMq recruited MSC more robustly than monocytes and CX alone (see Figure). Selective fibronectin integrin receptor blockade prevented MSC recruitment (*p&lt;0.05). Conclusions: CXMq has anti-inflammatory and pro-angiogenic properties that is potentially mediated by fibronectin.
Abstract 14277: Serum Nt-prob-type Natriuretic Peptide is Associated With Coronary Microvascular Dysfunction in Patients With Angina and Non-obstructive Coronary Artery Disease
Authors: Ali Ahmad, Jaskanwal D Sara, Michel T Corban, Takumi Toya, Ilke Ozcan, Lilach O Lerman, Amir LERMAN
Journal: Circulation (2020)

Title: Serum NT-proB-type Natriuretic Peptide is associated with Coronary Microvascular Dysfunction in Patients with Angina and Non-obstructive Coronary Artery Disease Authors: Ali Ahmad, MD, Jaskanwal D. Sara, MBChB, Michel T. Corban, MD, Takumi Toya, MD, Ilke Özcan, MD, Lilach O. Lerman, MD PhD, Amir Lerman, MD Introduction: Coronary microvascular dysfunction (CMD) is prevalent in patients with heart failure with preserved ejection fraction. Subclinical ischemia and myocardial fibrosis in CMD might raise filling pressure, a hallmark of HFpEF, which induces secretion of NT-proB-type natriuretic peptide (NTpro-BNP). We sought to explore the relationship between CMD and NT-proBNP. Methods: We studied 698 patients with signs and/or symptoms of ischemia and with non-obstructive CAD (&lt;40% angiographic stenosis) who underwent invasive CMD evaluation and had NT-proBNP checked within 6 weeks. CMD was defined as coronary flow reserve (CFR) (hyperemic flow/baseline flow as measured by the doppler wire) of ≤2.5 in response to intracoronary adenosine injection. Results: Overall mean age was 52.8±12.2 years, and women represented 69% of the patients. Log NT-proBNP showed a modest inverse correlation with CFR (Pearson’s R = -0.22, P&lt;0.0001; Figure 1 ), which remained significant after adjusting for age and gender (Standardized ß coefficient = -0.14; P = 0.001). Patients with CMD had higher levels of NT-proBNP than those without (82 [44-190] vs. 62 (33-130], P &lt;0.0001; Figure 2) . Conclusion: Declining coronary microvascular function is correlated with higher NT-proBNP levels. Patients with CMD had higher levels of NT-proBNP, a marker of elevated LV pressure, contributing to the possible role of CMD in early HFpEF pathophysiology. Keywords: Coronary microvascular dysfunction, NT-proBNP
Abstract 14663: High Rate of Arrhythmia Diagnoses Following Return of Pathogenic/likely Pathogenic Variants in an Unselected Population
Authors: Giovanni E Davogustto, Andrew Glazer, Christian M Shaffer, Eric Farber-Eger, Ozan Dikilitas, Shang Ning, Jennifer Pacheco, Jonathan Mosley, Sara Van Driest, Quinn Wells, Lauren L Rinke, Olivia Kalash, Yuko Wada, Sarah Bland, Zachary T Yoneda, Brett Kroncke, Kullo Iftikhar, Gail P Jarvik, Adam Gordon, eric B LARSON, Teri A Manolio, Tooraj Mirshahi, Jonathan Luo, Daniel Schaid, Bahram Namjou, Tarek ALSAIED, Rajbir Singh, Ashutosh Singhal, James D Ralston, Elizabeth M McNally, Albert George, Wendy Chung, David S Carrell, Kathleen A Leppig, Hakon Hakonarson, Patrick Sleiman, Sunghwan Sohn, Joseph Glessner, Joshua Denny, Wei-Qi Wei, M. Benjamin Shoemaker, Dan M Roden
Journal: Circulation (2020)

Background: Return of incidental genetic findings is recommended for pathogenic/likely pathogenic (P/LP) variants in Mendelian arrhythmia genes. The extent to which these variants are associated with arrhythmia phenotypes in unselected populations is unknown. Objective: Assess the impact of return of results (RoR) of P/LP variants in 4 arrhythmia genes in research participants not selected for cardiovascular disease. Methods: The cohort included 24,410 participants from the Electronic Medical Records and Genomics Network. Rare variants (minor allele frequency &lt;1%) in KCNE1 , KCNH2 , KCNQ1 , and SCN5A were identified and classified according to ACMG guidelines. Arrhythmia phenotypes extracted from electronic health records (EHRs) included atrial fibrillation/flutter (AF/AFL), conduction system disease, long QT syndrome (LQTS), ventricular tachycardia/fibrillation (VT/VF), and premature ventricular contractions (PVCs). P/LP carriers’ phenotypes were compared to non-carriers using logistic regression adjusted for demographic covariates and site. Participants with P/LP variants were informed of their results and the impact of this RoR was assessed after 1 year of follow-up clinical care. Results: The participants included 53.7% females and 72.5% white individuals, with a median age of 57 years. 71 participants had a heterozygous P/LP variant in one of the 4 genes. LQTS diagnoses were associated with P/LP carrier status for all 4 genes ( KCNE1 OR 22.8, p=1.0e-4; KCNH2 OR 35.1, p=1.8e-7; KCNQ1 OR 27.3, p=3.6e-18; SCN5A OR 5.6, p=0.02). Carriers of SCN5A P/LP variants were also more likely to have PVCs (OR 4.3, p=0.003). Sensitivity analyses showed the associations predated the RoR. EHRs included a diagnosis of LQTS or Brugada Syndrome in 11/71 (16%) pre-RoR, and 16 more were diagnosed after RoR (27/71, 38%). A total of 47/71 (66%) participants had a documented arrhythmia phenotype 1 year after RoR, although 20 of these participants were not diagnosed with an inherited arrhythmia syndrome. Conclusion: Inherited arrhythmia diagnoses could be established in nearly half of participants with P/LP variants. These data indicate that return of incidental P/LP variants in these genes may facilitate the early diagnosis of arrhythmias.
Surgeon Grow, an American in the Russian Fighting.
Journal: JAMA (1918)

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