bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aspirin use in central retinal arterial occlusion to prevent ischaemic stroke: a retrospective cohort study in Taiwan
Authors: Kang Eugene Yu-Chuan , Lin Yun-Hsuan , Wang Nan-Kai , Yeung Ling , Luo Caesar , Wu Wei-Chi , Sun Chi-Chin , Kang Je-Ho , Hung Ming-Jui , Chen Tien-Hsing 
Published: February 2019

ObjectiveTo understand the efficacy of aspirin use for preventing ischaemic stroke after central retinal artery occlusion (CRAO).DesignThe retrospective cohort study was conducted using the National Health Insurance Research Database from 1998 to 2013.SettingA population-based study.ParticipantsA total of 9437 participants with newly diagnosed CRAO were identified. Participants who had a previous stroke and/or retinal vascular occlusion, were aged <20 years and used aspirin 3 months before the event were excluded. There were 3778 eligible participants matched by propensity score, and they were divided into aspirin (n=434) and aspirin-naive (n=1736) groups after the matching.MethodsCox proportional hazard models and cumulative survival curves were used to assess ischaemic stroke in the study groups, along with log-rank tests to compare group differences.Main outcome measuresIncidence of ischaemic stroke in the aspirin and aspirin-naive groups 1 year after CRAO.ResultsOf the 3778 patients with newly diagnosed CRAO, 151 (4%) had a subsequent ischaemic stroke within 1 year. The risk was especially high during the first week of the CRAO. No difference between the aspirin and aspirin-naive groups was found in risk of ischaemic stroke, haemorrhagic stroke, gastrointestinal bleeding, major bleeding, acute coronary syndrome, retinal vein occlusion, new-onset glaucoma, undergoing panretinal photocoagulation or all-cause mortality. Risk factors for ischaemic stroke within 1 year of CRAO included male gender (p=0.031; HR=1.46) and age (p=0.032; HR=1.14).ConclusionsAspirin use after a CRAO showed no benefit on attenuating the risk of ischaemic stroke. The risk of ischaemic stroke was increased after CRAO especially during the first week. Male gender and age were risk factors for ischaemic stroke after CRAO.
Prevalence of early stages of heart failure in an elderly risk population: the Copenhagen Heart Failure Risk Study
Authors: Gaborit Freja Stoltze , Kistorp Caroline , Kümler Thomas , Hassager Christian , Tønder Niels , Køber Lars , Hansen Pernille Mørk , Kamstrup Pia Rørbæk , Faber Jens , Iversen Kasper Karmark , Schou Morten 
Published: February 2019

AimsTo describe the prevalence of heart failure (HF) stages in elderly outpatients with risk factors for HF but without known HF, and characterise the clinical, biochemical and echocardiographic findings in each stage.BackgroundEarly stages of HF are underdiagnosed; nevertheless, they are associated with an increased risk of hospitalisation and increased mortality. The prevalence of HF stages in elderly high-risk patients is unknown.MethodsA total of 400 patients were consecutively included: ≥60 years old, ≥1 risk factor for HF (diabetes, chronic kidney disease, cardiovascular disease, atrial fibrillation, hypertension), and without known or suspected HF. HF stages were defined as the following: stage A (risk factor for HF, normal echocardiography), stage B (abnormal echocardiography, without symptoms of HF) and stage C (abnormal echocardiography, symptoms of HF, clinical signs/increased plasma aminoterminal pro-B-type natriuretic peptide [NT-proBNP] concentrations).ResultsAfter thorough examination 44.25% of patients were categorised as HF stage A, 37.5% were HF stage B and 18.25% HF stage C. Those with higher stages of HF were older (p<0.001) and more often had atrial fibrillation (p=0.006). The median plasma NT-proBNP concentrations (pg/mL) were 132.5 for HF stage A, 275.5 for HF stage B and 400.0 for HF stage C (p<0.001). Detectable plasma troponin-I was more frequent with abnormal echocardiography: HF stage A 9.7%, HF stage B 27.3% and HF stage C 30.1% (p<0.001). HF stage C reported higher score on the Minnesota Living with Heart Failure Questionnaire (p<0.001).ConclusionsIn an elderly high-risk population without known or suspected HF, more than half were HF stage B or C. Higher stages of HF had increased plasma concentrations of NT-proBNP and troponin-I, besides a reduced quality of life. Focus on symptoms and signs of HF in this population are warranted.
Cardiovascular health technology assessment: recommendations to improve the quality of evidence
Authors: Berry Colin , Corcoran David , Mangion Kenneth 
Published: February 2019

The aim of this article is to review the role of Health Technology Assessment (HTA) organisations in appraising and recommending innovative cardiovascular technologies. We consider how bias impairs the quality of evidence from clinical trials involving cardiovascular healthcare technologies. Finally, we provide recommendations to HTA organisations to take account of bias when making guideline recommendations.Clinical research studies of medical devices, diagnostics and interventions in cardiovascular healthcare are susceptible to impairment through bias. While HTA organisations, such as the National Institute of Health and Care Excellence, may require reviewers to take account of bias, there are uncertainties as to how this is achieved, especially in cardiovascular technology trials. This becomes more relevant given that large trials are few in number; therefore, the quality of evidence from an individual trial may have a large bearing on guideline recommendations and clinical practice.HTA organisations should drive improvements in the design and rigour of randomised trials. The evolving landscape of cardiovascular healthcare technologies and related trials presents a challenge for HTA organisations and healthcare providers. The rapid turnover of evidence is externally relevant because the period from the trial publication to implementation of HTA guideline recommendations by healthcare providers may be prolonged, by which time new evidence may have emerged from subsequent trials. Implementation of a cardiovascular healthcare technology including be it a medical device, diagnostic or intervention may have profound implications for healthcare providers. These technologies may have high absolute costs and access may be influenced by socioeconomic and geographic factors.
Mechanical performance and healing patterns of the novel sirolimus-eluting bioresorbable Fantom scaffold: 6-month and 9-month follow-up by optical coherence tomography in the FANTOM II study
Authors: Simonsen Jo Krogsgaard , Holck Emil Nielsen , Carrié Didier , Frey Norbert , Lutz Matthias , Weber-Albers Joachim , Dudek Dariusz , Chevalier Bernard , Daemen Joost , Dijkstra Jouke , Fox Maule Camilla , Neghabat Omeed , Lassen Jens Flensted , Anderson Jeffrey , Christiansen Evald Høj , Abizaid Alexandre , Holm Niels Ramsing 
Published: February 2019

ObjectivesWe aimed to evaluate the mechanical properties and healing patterns 6 and 9 months after implantation of the sirolimus-eluting Fantom bioresorbable scaffold (BRS).BackgroundThe Fantom BRS (Reva Medical, San Diego, USA) has differentiating properties including radiopacity, strut thickness of 125 µm, high expansion capacity and has demonstrated favourable mid-term clinical and angiographic outcomes.Methods and resultsFANTOM II was a prospective, single arm study with implantation of the Fantom BRS in 240 patients with stable angina pectoris. Guidance by optical coherence tomography (OCT) was encouraged and was repeated at 6-month (cohort A) or 9-month follow-up (cohort B). Matched baseline and follow-up OCT recordings were available in 152 patients. In-scaffold mean lumen area in cohort A was 6.8±1.7 mm2and 5.7±1.4 mm2at baseline and follow-up (p<0.0001) and was 7.2±1.6 mm2and 5.6±1.4 mm2in cohort B (p<0.0001). Mean scaffold area remained stable from 7.1±1.5 mm2at baseline to 7.2±1.4 mm2at 6 months (p=0.12), and from 7.4±1.5 mm2to 7.3±1.4 mm2at 9 months. Strut malapposition was median 0.8 (IQR 0.0;3.5)% and 1.8 (IQR 0.3;6.0)% at baseline and was 0.0 (IQR 0.0;0.0)% in both groups at 6-month and 9-month follow-up. Strut tissue coverage was 98.1 (IQR 95.9;99.4)% at 6 months and 98.9 (IQR 98.3;100.0)% at 9 months.ConclusionsThe novel Fantom BRS had favourable healing patterns at 6-month and 9-month follow-up as malapposition was effectively resolved and strut coverage was almost complete. The scaffold remained stable through follow-up with no signs of systematic late recoil.
Intestinal iNKT cells migrate to liver and contribute to hepatocyte apoptosis during alcoholic liver disease
Authors: Lee Kuei-Chuan , Chen Peng , Maricic Igor , Inamine Tatsuo , Hu Jingjuan , Gong Shenhai , Sun Julia C. , Dasgupta Suryasarathi , Lin Han-Chieh , Lin Yi-Tsung , Loomba Rohit , Stärkel Peter , Kumar Vipin , Schnabl Bernd 
Published: February 2019

We investigated the migration of intestinal immune cells to the liver and their contribution to alcoholic liver disease. In mice fed ethanol, we found that an increased number of invariant natural killer T (iNKT) cells, which respond to the antigen presented by CD1d, migrated from mesenteric lymph nodes to the liver. iNKT cells react to lipid antigens, so we studied their activities in mice with intestinal epithelial cell-specific deletion of Pparg ( PpargΔIEC) as a model for altering intestinal lipidomic profiles. Levels of CD1d increased in intestines of ethanol-fed PpargΔIEC mice, and in cell-tracking experiments, more iNKT cells migrated to the liver, compared with mice without disruption of Pparg. Livers of PpargΔIEC mice had increased markers of apoptosis and liver injury after ethanol feeding. iNKT cells isolated from livers of ethanol-fed PpargΔIEC mice induced apoptosis of cultured hepatocytes. An inhibitor of iNKT cells reduced ethanol-induced liver injury in PpargΔIEC mice. Duodenal tissues from patients with alcohol-use disorder have been found to have increased levels of CD1d compared with tissues from patients without alcohol overuse. Ethanol use, therefore, activates iNKT cells in the intestine to migrate to liver, where they—along with the resident hepatic iNKT cells—contribute to hepatocyte death and injury. NEW & NOTEWORTHY In this article, we studied migration of intestinal immune cells into the liver in response to ethanol-induced liver disease. We found that chronic ethanol feeding induces expression of CD1d by enterocytes, which activate invariant natural killer T (iNKT) cells in mesenteric lymph nodes; activation is further increased with loss of peroxisome proliferator-activated receptor gamma gene and altered lipid profiles. The activated iNKT cells migrate into the liver, where they promote hepatocyte apoptosis. Patients with alcohol use disorder have increased expression of CD1d in the small intestine. Strategies to block these processes might be developed to treat alcoholic liver disease.
Effect of Trendelenburg position and lower-body positive pressure on neck fluid distribution
Authors: Yadollahi Azadeh , Singh Bhajan , Millar Philip J. , Vena Daniel , Floras John S. , Bradley T. Douglas 
Published: February 2019

Fluid that shifts out of the legs and into the neck when supine can contribute to upper-airway narrowing. The present study investigates the relative contributions of vascular and extravascular fluid to the total accumulation of neck fluid volume (NFV). In 22 healthy awake participants (8 women), aged 42 ± 9 yr, we measured NFV with bioelectrical impedance, internal jugular vein volume (IJVV) with ultrasound, and extravascular NFV (NFVEV) as the difference between NFV and IJVV. Participants were randomly allocated to control and intervention, both of which were conducted on the same day. Measurements were made at baseline and every 5 min thereafter during control and intervention. During intervention, participants received 40 mmHg lower-body positive pressure (LBPP) when supine, followed by LBPP plus 10° Trendelenburg position, then LBPP when supine again, followed by recovery. During control, participants lay supine for equal time. LBPP and LBPP plus Trendelenburg position both increased NFV from baseline compared with control ( P < 0.001), with significant contributions from IJVV ( P < 0.001). Returning to supine with LBPP, IJVV returned to baseline, but NFV remained elevated because of accumulation of NFVEV. These findings suggest that contributions of IJVV to NFV are immediate but transient, whereas sustained elevation in NFV when supine is likely a result of NFVEV. These findings add new insights into the mechanism by which fluid accumulates in the neck by rostral fluid shift. NEW & NOTEWORTHY This study demonstrates that lying supine for 30 min as well as increased fluid shift out of the legs to simulate nocturnal rostral fluid shift causes fluid to accumulate mainly in the extravascular space of the neck rather than in the internal jugular veins. Therefore, in subjects without fluid-retaining states, extravascular neck fluid accumulation overnight might play a more significant role in the pathophysiology of upper-airway narrowing than intravascular fluid accumulation.
Transthoracic Pulmonary Artery Denervation for Pulmonary Arterial Hypertension
Authors: Huang Yuan , Liu Yi-Wei , Pan Hai-Zhou , Zhang Xiao-Ling , Li Jun , Xiang Li , Meng Jian , Wang Pei-He , Yang Jun , Jing Zhi-Cheng , Zhang Hao 
Published: February 2019

Objective—
Pulmonary arterial hypertension is characterized by progressive pulmonary vascular remodeling and persistently elevated mean pulmonary artery pressures and pulmonary vascular resistance. We aimed to investigate whether transthoracic pulmonary artery denervation (TPADN) attenuated pulmonary artery (PA) remodeling, improved right ventricular (RV) function, and affected underlying mechanisms. We also explored the distributions of sympathetic nerves (SNs) around human PAs for clinical translation.

Approach and Results—
We identified numerous SNs in adipose and connective tissues around the main PA trunks and bifurcations in male Sprague Dawley rats, which were verified in samples from human heart transplant patients. Pulmonary arterial hypertensive rats were randomized into TPADN and sham groups. In the TPADN group, SNs around the PA trunk and bifurcation were completely and accurately removed under direct visualization. The sham group underwent thoracotomy. Hemodynamics, RV function, and pathological changes in PA and RV tissues were measured via right heart catheterization, cardiac magnetic resonance imaging, and pathological staining, respectively. Compared with the sham group, the TPADN group had lower mean pulmonary arterial pressures, less PA and RV remodeling, and improved RV function. Furthermore, TPADN inhibited neurohormonal overactivation of the sympathetic nervous system and renin-angiotensin-aldosterone system and regulated abnormal expressions and signaling of neurohormone receptors in local tissues.

Conclusions—
There are numerous SNs around the rat and human main PA trunks and bifurcations. TPADN completely and accurately removed the main SNs around PAs and attenuated pulmonary arterial hypertensive progression by inhibiting excessive activation of the sympathetic nervous system and renin-angiotensin-aldosterone system neurohormone-receptor axes.
Tuning the Thromboinflammatory Response to Venous Flow Interruption by the Ectonucleotidase CD39
Authors: Anyanwu Anuli C. , Kanthi Yogendra , Fukase Keigo , Liao Hui , Mimura Tekashi , Desch Karl C. , Gruca Martin , Kaskar Saabir , Sheikh-Aden Hussein , Chi Liguo , Zhao Raymond , Yadav Vinita , Wakefield Thomas W. , Hyman Matthew C. , Pinsky David J. 
Published: February 2019

Objective—

Leukocyte flux contributes to thrombus formation in deep veins under pathological conditions, but mechanisms that inhibit venous thrombosis are incompletely understood. Ectonucleotide di(tri)phosphohydrolase 1 (
ENTPD1
or
Cd39
), an ectoenzyme that catabolizes extracellular adenine nucleotides, is embedded on the surface of endothelial cells and leukocytes. We hypothesized that under venous stasis conditions, CD39 regulates inflammation at the vein:blood interface in a murine model of deep vein thrombosis.

Approach and Results—

CD39-null mice developed significantly larger venous thrombi under venous stasis, with more leukocyte recruitment compared with wild-type mice. Gene expression profiling of wild-type and
Cd39
-null mice revealed 76 differentially expressed inflammatory genes that were significantly upregulated in
Cd39
-deleted mice after venous thrombosis, and validation experiments confirmed high expression of several key inflammatory mediators. P-selectin, known to have proximal involvement in venous inflammatory and thrombotic events, was upregulated in
Cd39
-null mice. Inferior vena caval ligation resulted in thrombosis and a corresponding increase in both P-selectin and VWF (von Willebrand Factor) levels which were strikingly higher in mice lacking the
Cd39
gene. These mice also manifest an increase in circulating platelet-leukocyte heteroaggregates suggesting heterotypic crosstalk between coagulation and inflammatory systems, which is amplified in the absence of CD39.

Conclusions—
These data suggest that CD39 mitigates the venous thromboinflammatory response to flow interruption.
Influence of Sex on Relationship Between Total Anatomical and Physiologic Disease Burdens and Their Prognostic Implications in Patients With Coronary Artery Disease
Authors: Kim Chee Hae , Koo Bon‐Kwon , Lee Joo Myung , Shin Eun‐Seok , Park Jonghanne , Choi Ki Hong , Hwang Doyeon , Rhee Tae‐Min , Zhang Jinlong , Choi You‐Jung , Lee Seo‐Young , Choi Jin‐Ho , Doh Joon‐Hyung , Nam Chang‐Wook , Wang Jianan , Chen Shaoliang , Kuramitsu Shoichi , Tanaka Nobuhiro , Matsuo Hitoshi , Akasaka Takashi 
Published: February 2019

Background
Total atherosclerosis disease burden is associated with clinical outcomes in patients with coronary artery disease. However, the influence of sex on the relationship between total anatomical and physiologic disease burdens and their prognostic implications have not been well defined.

Methods and Results

A total of 1136 patients who underwent fractional flow reserve (FFR) measurement in all 3 major coronary arteries were included in this study. Anatomical and physiologic total disease burden was assessed by SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score, residual SYNTAX score, a total sum of FFR in 3 vessels (3‐vessel FFR), and functional SYNTAX score. The primary end point was major adverse cardiac events, a composite of cardiac death, myocardial infarction, and ischemia‐driven revascularization at 2 years. There were no differences in angiographic diameter stenosis, SYNTAX score, or residual SYNTAX score between women and men. However, both per‐vessel FFR (0.89±0.10 versus 0.87±0.11,
P
<0.001) and 3‐vessel FFR (2.72±0.13 versus 2.69±0.15,
P<
0.001) were higher in women. Multivariable Cox regression analyses showed that total anatomical and physiologic disease burdens were significantly associated with 2‐year major adverse cardiac events, and there was no significant interaction between sex and total disease burden for clinical outcomes.

Conclusions
Despite similar angiographic disease severity, both per‐vessel and per‐patient physiologic disease severity was less in women than in men. There was no influence of sex on prognostic implications of total anatomical and physiologic disease burdens in patients with coronary artery disease.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01621438.
Abstract 112: Doxorubicin Alters Cardiac Fibroblast Phenotype
Authors: Mancilla Trevi R , Aune Gregory J 
Published: February 2019

The oldest cohort of childhood cancer survivors are entering into their sixth decade. The milestone comes with the knowledge that this population is at a 15 times greater risk of cardiovascular events than the general population. One factor in this is doxorubicin, a chemotherapeutic drug commonly used to treat pediatric cancers. Our study investigates the effect of doxorubicin on proliferating cells in the heart, specifically, cardiac fibroblasts.
Doxorubicin inhibits cardiac fibroblast growth and migration. Cardiac fibroblasts also undergo a shift in gene expression when exposed to doxorubicin. Inflammatory cytokines and their receptors are upregulated, along with extracellular matrix regulatory proteins. ECM structural proteins and adhesion molecules are downregulated compared to control cells. Of note, monocyte chemoattractant protein-1, and its receptor C-C motif chemokine receptor-4, are upregulated over 40-fold compared to control cells.
Doxorubicin has multiple mechanisms of actions that target proliferating and non-proliferating cells differently. Cardiac fibroblasts are proliferative cells with a major role in multiple processes of cardiac homeostasis. This study lays the foundation of the phenotypic changes cardiac fibroblasts undergo when exposed to doxorubicin. These changes may create a microenvironment that primes the heart for adverse cardiac remodeling.
Abstract 336: Human Bone Contains Primitive Cells With Angiogenic and Immunomodulatory Properties
Authors: Kubo Hajime , Feldsot Eric , Schena Giana , Hobby Alexander , Yang Yijun , Johnson Jaslyn , Gross Polina , Sharp Thomas , Mohsin Sadia , Berretta Remus , Choi Eric T , Donnelly Joanne , Christopher Hydel , Houser Steven R 
Published: February 2019

Previously, we have shown that treatments of cortical bone derived stem cells (CBSCs) reduce ventricular remodeling and improve cardiac functions in both mouse and pig myocardial infarction (MI) models. The goals of the present study were to isolate and characterize human CBSCs (hCBSCs).
Using bone fragments obtained at the time surgeries, we isolated three morphologically distinctive hCBSC phenotypes; 1) sphere forming (SF); 2) epithelial like monolayer (ELM); and 3) larger and spindle shaped (LSS) phenotype. The hCBSC phenotypes grew without senescence in culture. Mean doubling time (hour) for SF, ELM, and LSS at the passage number 20 (P20) were 19.54, 21.21, and 20.3 respectively and at the P40 were 18.01, 17.13, and 20.56 respectively. All of the phenotypes were found to have surface expression of CD44; however, other markers detected (CD105, CD90, CD73, CD106, CD271, and CD133) on mouse CBSCs (mCBSCs) were not detected along with the markers not detected on the surface of mCBSCs (CD45, CD11b, CD31, CD34, CD117, and CD325). Erythrocytes (CD235a) and immune cell markers (CD2, CD3, CD14, CD16, CD19, and CD56) were also not detected. The hCBSCs were found without histocompatibility antigen Ia (MHC-Ia: HLA-A, HLA-B, and HLA-C) and MHC-II (HLA-DR); instead, they expressed soluble forms of MHC-Ib (HLA-G5, HLA-G6, and HLA-G7), potent inhibitor of natural killer cells and other immune cells. These features are commonly found in immune privileged cells. Further, the hCBSCs produced the immunomodulatory and anti-inflammatory factors (IL-4, IL-1RA, TGF-b and IL-10). Additionally, the hCBSCs secreted angiogenic factors that organize endothelial cells into tube like structures.
From these results, the hCBSCs we isolated have totally different surface marker characteristics compared to any other known cells including mCBSCs. In addition to their angiogenic effects, the hCBSCs have immunomodulatory properties that could make them suitable for cell therapy targeting inflammatory diseases such post myocardial infarction remodeling.