bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 594: Characterization of Anti-thrombotic and Anti-inflammatory Properties of New Synthetic, Protamine Reversible Low Molecular Weight Heparin
Authors: Chandarajoti Kasemsiri , Sparkenbaugh Erica M , Key Nigel S , Xu Yongmei , Cooley Brian , Liu Jian , Pawlinski Rafal 
Published: March 2022

Low-molecular-weight heparins (LMWHs) are carbohydrate-based anticoagulants clinically used to treat thrombotic disorders; however, lack of full reversibility with protamine and clearance by kidney limit treatment options. Recently we have developed a chemoenzymatic method to synthesize a new synthetic dodecasaccharide (12mer) with high anti-factor Xa (FXa) activity which was protamine reversible in vitro and in vivo.
In the current study, we further characterized the pharmacokinetic, anti-thrombotic and anti-inflammatory properties of this compound using various mouse models. First, time course (0.5, 1, 2, 4, 8 hours, n=4) and dose response (0.5, 1, 1.5, 2.0 mg/kg, n=4) studies in C57Bl/6J mice showed that FXa activity was inhibited by 12mer in vivo and the half-life of the compound injected s.c. at the dose of 1.5 mg/kg was 3 hours. 12mer was cleared from the circulation by 8 hours.
Furthermore, fibrin accumulation observed in the femoral vein 60 minutes after electrolytic injury (2.99 ± 1.16; p<0.05; normalized relative fluorescent intensity to control mouse, mean ± SD), was similarly reduced by 12mer (0.6 mg/kg, 1.63± 0.48), UFH (150 U/kg, 1.26 ± 0.35) and enoxaparin (1 mg/kg, 1.39 ± 0.85, p<0.05 for all). Importantly, protamine reversed the anti-thrombotic effect of 12mer and returned fibrin accumulation to normal levels (2.69 ± 0.87; p < 0.05 vs.12mer alone).
Finally, we investigated if 12mer can inhibit thrombotic and inflammatory effect of FXa, previously demonstrated by us in the Berkeley mouse model of sickle cell disease. Sickle mice received subcutaneous injection of saline (n=6) or 12-mer (n=6; 2.0 mg/kg) every 8 hours for 7 days. Compared to saline, 12mer reduced plasma levels of thrombin anti-thrombin complexes (8.2±1.4 vs 4.4±1.3 ng/mL; p=0.07, mean ± S.E.M), IL-6 (5.5±1.5 vs 1.1±0.4 pg/mL, p<0.05) and sVCAM1 (1.1±0.2 vs 0.6±0.07 μg/mL, p< 0.05) in sickle mice. Together, our data demonstrates that chemoenzymatic synthesis offers a promising approach toward obtaining new, protamine-reversible LMWHs with excellent anti-coagulant and anti-inflammatory properties.
Abstract 610: Microrna-146a Accumulates in the Atherosclerotic Plaque but Decreases in Circulation of Patients With ST Segment Elevation MI
Authors: Gray Warren D , Corrigan Frank E , Mitchell Adam , Alexy Tamas , Rooney Kim , Garcia-Bengochea Youssef , Devireddy Chandan , Jaber Wissam , Liberman Henry , Finn Aloke , Searles Charles , Kumar Gautam 
Published: March 2022

MicroRNAs (miRNAs) function as regulators of gene expression intracellularly or as paracrine signals extracellularly. Their role in modulation of cardiovascular disease is emerging. Changes in miRNA profiles have been characterized in the circulation of patients with myocardial infarction (MI), but little is known of the correlation between circulating and plaque miRNAs during atherosclerosis progression and ST-elevated MI (STEMI). During percutaneous interventions (PCI), angioplasty catheter balloons can retain plaque debris post-inflation and may provide insight into plaque miRNA expression in disease.
Our objective was to assess the correlation between miRNA levels in circulation and plaques of patients with coronary artery disease (CAD), including those with ST segment elevation MI (STEMI).
We collected balloons and plasma from patients undergoing PCI for STEMI (n=6) or elective cardiac catheterization (n=2). Plasma was collected from age and sex-matched patients at low risk for CAD (n=5) or with stable CAD (n=6). RNA was extracted from balloon-adherent debris and patient plasma and sequenced. miRNA levels were validated by qRT-PCR.
Deep sequencing of patient plasma suggested a decrease in levels of circulating miR-146a-5p in STEMI patients (fig A). This miRNA is found in several cell types (endothelial cells, immune cells, and macrophages), and targets inflammatory signaling pathways. Via PCR, we found that levels of circulating miR-146a dropped markedly both in patients with stable CAD and STEMI (fig B). However, the trend was reversed in plaques; miR-146a levels increased 15-fold from stable to ruptured plaques (fig C). We postulate that miR-146a accumulation in plaques is a compensatory response to inflammation, but that the drop in circulating miR-146a levels may contribute to atherosclerotic plaque instability. These findings have implications for development of miRNA-based strategies for diagnosis and management of vulnerable plaques.
Abstract 716: Echocardiographic Evidence of Systemic Atherosclerosis and Long-Term Outcomes in Patients with Non-Hemorrhagic Stroke
Authors: Pieper Justin , Ashamalla Michael , Yager Neil , Sedhom Daniel , Ghate Ketan , Nguyen Veronica , Shkolnik Boris , Torosoff Mikhail 
Published: March 2022

Background:
Echocardiography is routinely performed for evaluation of cardiac embolic causes in patients with non-hemorrhagic stroke. However, added value of echocardiographic evidence for systemic atherosclerosis in patients with known peripheral disease and non-hemorrhagic stroke has not been well established.

Material and Methods:
Retrospective chart review was performed in 517 consecutive patients treated for non-hemorrhagic stroke at a single academic medical center. Complete transthoracic echocardiograms were reviewed for presence of mitral annular calcifications, valve sclerosis, or aortic atherosclerosis. Long-term outcomes were ascertained through the National Death Index. This study was approved by the institutional IRB.

Results:
The study cohort included 48% females. Coronary artery disease (CAD) was present in 27%, hypertension in 62%, diabetes in 20%, dyslipidemia in 38%, peripheral vascular disease (PVD) in 4%, and end-stage renal disease in 5%. Echocardiographic evidence of systemic atherosclerosis was noted in 43%.

We observed 28% mortality at the mean follow-up length of 46+/-20 months. Mortality was significantly increased in older patients, and in patients with histories of end-stage renal disease (p=0.048), PVD (p<0.001), diabetes (p=0.05), hypertension (p=0.027), and CAD (p=0.012). Echocardiographic evidence of systemic atherosclerosis was associated with a 2-fold increase in mortality (20 vs. 40%, p<0.0001).
In multivariate logistic regression analysis, when adjusted for recorded end-points, the echocardiographic evidence of systemic atherosclerosis was not predictive of adverse outcomes. Only age (HR 1.9, 95%CI 1.6-2.4, p<0.0001), diabetes (HR 1.9, 95% CI 1.1-3.3, p=0.029), and PVD (HR 5.1, 95%CI 1.8-14.4, p=0.0024) were associated with increased mortality.

Conclusions:
In patients with non-hemorrhagic stroke, systemic evidence of atherosclerosis suggested by transthoracic echocardiography is not associated with worse long-term prognosis. This should not preclude providers from performing an echocardiographic evaluation if clinically indicated. The question of diagnostic utility for post stroke transthoracic echocardiography is an important topic and warrants further study.
Abstract 81: A retrospective analysis of 274 cases of Kawasaki disease
Authors: Goto Kenjiro 
Published: March 2022

Purpose:
Haematological, biochemical and clinical parameters were retrospectively analysed in a group of patients with Kawasaki disease, to determine predictive variables on the effect of intravenous immunoglobulin (IVIG) therapy.

Methods:
We studied 274 cases of Kawasaki disease between October 2006 and September 2013 at a single centre (Kawasaki Municipal Tama Hospital, Japan). These cases were analysed on the basis of:

(1) Requirement of additional therapy post IVIG (41 cases vs 200 cases not requiring additional therapy)
(2) Presence of coronary artery lesions (CAL: Z score≧2.5) within a month (15 cases with CAL, 220 cases without CAL)
Haematological, biochemical and clinical parameters including white blood cell, percentage of neutrophils, platelet, total-bilirubin, AST, ALT, Albumin, Sodium, C-reaction protein, Fibrinogen and D-dimmer as well as time to first post-IVIG treatment were compared in the categories shown above. Statistical analysis was performed with Mann-Whitney U test. Differences were considered to be significant when the two-tailed p-value was < 0.05.

Results:
The percentage of neutrophils, total-bilirubin, AST, ALT, Albumin, Sodium, C-reaction protein, D-dimmer and time to first treatment show significant difference between the groups stratified on the requirement of post-IVIG therapy. In the stratification based on acute CAL- AST, ALT, Albumin and Sodium show significant difference between the groups.

Conclusion:
We suggest that ratio of neutrophil, total-bilirubin, AST, ALT, Albumin, Sodium, C-reaction protein, D-dimmer and time to first treatment are predictive factors of resistance to single IVIG therapy. Similarly, levels of AST, ALT, Albumin and Sodium are predictive factors of acute coronary artery lesions in Kawasaki disease.
Abstract 96: Changes In HDL Cholesterol During The Acute Phase of Kawasaki Disease
Authors: Nihei Koichi , Ito Chieko , Park Juhyon , Mishima Noriko , Nakamura Hiroaki , Nasuno kiyoto , Fujiwara Junko , Sekine Takashi 
Published: March 2022

To determine the correlations between changes in high-density lipoprotein cholesterol (HDL-C) and other blood variables during the acute phase of Kawasaki disease (KD), we investigated changes in the plasma level of HDL-C, serum apolipoproteins and number of peripheral blood monocytes. 26 Japanese patients with KD were subjects of this study. Plasma HDL-C decreased during the 1st week of illness, and increased during the 2nd week. The mean levels of minimum HDL-C in KD patients treated with total intravenous immunoglobulin (IVIG) dose ≧ 4g/kg, was significantly lower than those treated with total IVIG dose < 4g/kg (p=0.0005). There was a strong direct correlation between minimum HDL-C in KD patients and HDL-C on 5th day of KD onset (r=0.71, p < 0.0001). Assessing the performance of plasma HDL-C on 5th day of KD onset in predicting the necessity for high-dose IVIG treatment to KD, ROCs were plotted and the AUC was 0.82. A cutoff value of 16mg/dl had a specificity of 0.82 and sensitivity of 0.80 for predicting those.
The apo A-I and A-II levels were correlated with plasma HDL-C, respectively. And the peripheral blood monocytes counts which correlated with serum levels of macrophage-colony stimulating factor, were not correlated with plasma HDL-C.
Plasma HDL-C levels during the 1st week of illness might serve as a predictor for non-responder to low-dose IVIG treatment in patients with acute KD.
Abstract O.09: French observatory of Kawasaki disease in adults: 24 observations.
Authors: Fraison Jean-Baptiste , Seve Pascal , Gommard-Menesson Emmeline , Dauphin Claire , Mahr Alfred , Landron Cedric , Nathalie Costedoat-Chalumeau , Epaulard Olivier , Boutin Le Thi Huong , Piram Maryam , Mékinian Arsène , Roblot Pascal , Oziol Eric , Hot Arnaud , Chalhoub Gihane , Galempoix Jean-Marc , Marchand Guillaume , Humbert Sébastien , Humbert Philippe , Morlat Philippe , Puéchal Xavier , Guillevin Loic , Koné-Paut Isabelle , Fain Olivier 
Published: March 2022

Introduction:
Kawasaki disease (KD) is a vasculitis that occurs mostly among children and exceptionally in adults. We report data from a French observatory of adult KD.

Patients and methods:
Adult patients diagnosed with KD in 16 French centers were included. Patients were classified as complete KD or incomplete KD according to IKDC or probable KD.

Results:
We included 24 patients with a median age of 29 years (22-39) and a sex ratio (M / F) 2.42, 12 complete KD, 9 incomplete KD and 3 probable KD without any other cause. Time to diagnosis was 13 days (10-20.5). Main events were: fever (100%), extremities changes (21/24, 87.5%), rash (22/24, 92%), conjunctivitis (16/24, 16, 66%), cheilitis (15/24, 63%), strawberry tongue (11/24, 46%), adenopathy (10/24, 42%), cardiac abnormalities (11/24, 46%), cardiogenic shock (n = 1), myo-pericarditis (n = 3) and left heart failure (n = 1).

Median CRP was 228mg/L (166-311), SGOT: 68 IU/L (51-139), SGPT: 125 IU/L (69-190), platelets 372 G/L (209-630) and leukocytes 16 G/L (8.3-20).
Cardiac involvement was researched in 23 patients (96%) by achieving: echocardiography (20/24), coronary scanners (6/24), coronary angiography (5/24), cardiac MRI (2/24) and stress tests (2/24).
An arteritic vascular disease was found in 11 patients (46%): coronary aneurysms (8/24, 33%), coronary arteritis (10/24; 42%) and peripheral arteritis (2/24, 8.3%) with acute lower limb ischemia (1/24, 4.2%) and splenic infarction (1/24, 4.2%).

Patients received:
intravenous immunoglobulin (17/24; 71%): aspirin (21/24, 88%).

After 6 months, it persisted 5 aneurysm (20.8%). Complications noticed during the last follow-up were: heart failure (1/24, 4.3%), aneurysm (3/24, 12.5%).

Conclusion:
The adult KD is a rare disease that can have bad prognosis in short or long term and leave irreversible damage. The high rate of cardiac complication could be due to the long diagnosis delay, the absence of the gold standard treatment in 30% of cases or a selectional bias due to the difficulty to diagnose this disease in adulthood.
Abstract 16904: Are All Omega-3s Created Equal? Comparison of the Bioavailability and Efficacy of Four Omega-3 Preparations
Authors: Butt Rodney W , Cockerline Carla A , Rowe William J , Laidlaw Maggie 
Published: March 2022

There are many omega-3 products available in the prescription and non-prescription marketplace. Neither health care professionals nor consumers may be aware of the potential influence of the manufacturing processes and source(s) of the starting material. Manufacturers of the various omega-3 preparations imply that their product is superior to others, based on its structural characteristics, whether phospholipid, triglyceride or ethyl ester.
The objective of this study was to compare the ability of four (4) different omega-3 preparations to raise whole blood fatty acid levels. This was a Prospective, Open-label, Blinded Endpoint (PROBE), four period, cross-over study. Thirty-five (35) healthy subjects were randomized to consume one of four test articles for four weeks, followed by a four-week washout, and this process was repeated until all products had been consumed by all subjects. The test article doses were based on their label specifications. The four products and daily doses were:
Triglyceride fish oil:
EPA of 650 mg, DHA of 450 mg
Ethyl Ester fish oil:
EPA of 756 mg, DHA of 228 mg
Phospholipid krill oil:
EPA of 150 mg, DHA of 90 mg
Triglyceride salmon oil:
EPA of 180 mg, DHA of 220 mg
Blood samples before and after supplementation were quantified for whole blood fatty acids by gas chromatography flame ionization. Bioavailability was assessed for each product individually, based on its change from baseline. Percentage change from baseline was then compared across all four products.
TG fish oil was statistically superior to all of its comparators in the bioavailability of EPA+DHA, and of DHA alone. Its EPA percentage increase was more than four times that of PL krill oil and TG salmon oil. Only the two TG products significantly increased whole blood
DHA levels. For investigators and clinicians, the type and dose of omega-3s may be clinically important when assessing potential clinical impact.
Abstract 17326: Clues to Attenuating Plaque Inflammation: Heat Shock Protein-27 Augments Macrophage Histone Deacetylase-6 Activity and Cytoskeletal Migratory Capacity
Authors: Koumbadinga Gérémy A , Alvarez-Omeldo Daiana , O’Brien Edward R 
Published: March 2022

Introduction:
We recently demonstrated that elevated serum levels of Heat Shock Protein 27 (HSP27) are associated with reduced 5-year CV events and that extracellular HSP27 attenuates experimental atherogenesis and lesion progression. Indeed, HSP27 therapy reduces plaque macrophage and cholesterol content and enhances histological features associated with resilience to plaque rupture. Cell motility and adhesion involves dynamic microtubule acetylation/deacetylation, a process regulated by the enzyme histone deacetylase 6 (HDAC6), a major cytoplasmic α-tubulin deacetylase. We hypothesize that HSP27 enhances HDAC6 activity to promote favorable plaque remodeling by enhancing macrophage migration.

Methods / Results:
1. The HDAC6 activity of THP-1 macrophages treated with recombinant HSP27 was assessed using a fluorescent plate reader ELISA. In a dose-dependent fashion, rHSP27 treatment resulted in a 100% increase in HDAC-6 activity compared to the control and was independent of HSP27 phosphorylation. Moreover, HDAC-6 activity was enhanced 100% in peritoneal macrophages harvested from rHsp27-treated ApoE-/- vs. control mice. With the addition of cycloheximide HDAC-6 activity was not prolonged, suggesting that HSP27 did not have an effect on the enzymatic half-life.

2. When HSP27 expression was knocked down in THP-1 cells transfected with a lentivirus carrying specific shRNA-HSP27 vector there was a reduction in HDAC6 activity and an increase in tubulin acetylation - and both of these effects were rescued with the addition of rHSP27.
3. Using a Boyden chamber cell migration assay, we found that rHSP27 treatment increased migration of THP-1 cells without and with ox-LDL loading by ~2- and ~1.5-fold; respectively - an effect that was blocked by either Tubacin (a specific inhibitor of HDAC6) or HSP27 knockdown.

Conclusion:
Extracellular HSP27 is capable of up-regulating HDAC6 activity in macrophages, an effect associated with enhanced macrophage migratory capacity. These data suggest that HSP27 may be important for potentially improving macrophage egress from plaques thereby resulting in reduced cholesterol content and more stable lesions - factors that may explain the proven predictive biomarker value of elevated serum HSP27 levels.
Abstract 17459: Recurrent In-stent Thrombosis: An Atypical Presentation of Malignancy
Authors: Klein Evan C , Crabbe Deborah L 
Published: March 2022

Management of acute coronary syndromes most typically involves percutaneous coronary intervention with or without stent placement, and this has significantly improved morbidity and mortality in this syndrome. However, intra-coronary stents can lose their patency due to either in-stent restenosis or in-stent thrombosis (IST). More rarely recurrent in-stent thrombosis (RIST) can occur.
Here we report the case of a 58 year old African American male with a history of human immunodeficiency virus (on highly active antiretroviral therapy), chronic kidney disease, cerebrovascular accident, chronic obstructive pulmonary disease and tobacco abuse. He presented with 7 non-ST-elevation myocardial infarctions, 6 angiographically documented episodes of coronary artery occlusion and 2 episodes of early in-stent and 2 late in-stent thromboses over the span of less than 7-months. This occurred despite reasonable evidence for compliance with optimal medical therapy. His antiplatelet regimen was changed several times until he presented 1-month after his final IST with gastrointestinal bleeding from a fungating partially obstructing well to moderately differentiated invasive adenocarcinoma in the ascending colon. Unfortunately, he expired 2-months later.
Including our patient there have now been 4 reports of early RIST in patients with undiagnosed malignancy. Specific malignancies reported include: prostate, adrenal, renal, bladder, and now gastrointestinal primaries. Trousseau’s syndrome, the prothrombotic state of malignancy, has long been implicated in both venous and arterial thrombosis. We believe this prothrombotic milieu also increases the risk for in-stent thrombosis.
In the setting of malignancy, as with myocardial infarction, delay before diagnosis can be catastrophic. While more data is needed on the topic, for now we suggest that physicians consider aggressive screening for malignancy in patients with IST or RIST.
Abstract 17798: Statin Persistence After Reported Adverse Reactions and Patient Outcomes
Authors: Zhang Huabing , Plutzky Jorge , Shubina Maria , Turchin Alexander 
Published: March 2022

Evidence suggests that many patients tolerate statin therapy after an adverse reaction. However, clinical outcomes of statin persistence after adverse reactions are unknown.
We conducted a retrospective cohort analysis of the relationship between persistent statin therapy during 12 months after an adverse reaction, and cardiovascular (CV) events (myocardial infarctions and strokes) and death from any cause. We studied patients in primary care practices at two academic medical centers who reported an adverse reaction to a statin between 2000 and 2011 and were subsequently followed for at least 12 months. Adverse reactions to statins were identified using a combination of natural language processing of provider notes and EMR data.
Among 28,279 study patients, 19,997 (70.7%) had persistent statin therapy after an adverse reaction. There were 10,203 (36.1%) patients at high CV risk (previous history of coronary artery disease (CAD), stroke or diabetes). Over a mean of 1,333 days of follow-up, 2,390 (8.45%) of patients suffered a CV event and 1,354 (4.8%) patients died.
In univariate analysis, among patients at high CV risk 25.7% of patients who stopped statins reached composite primary outcome (CV event or death) vs. 19.6% of patients who had persistent statin therapy (Figure; p < 0.0001). In multivariable analysis adjusted for demographics, smoking status, Charlson Comorbidity Index, family history of stroke or CAD, blood pressure, body mass index, LDL cholesterol level, and renal function, persistent statin therapy was associated with a hazard ratio for primary outcome of 0.887 (95% CI 0.807 - 0.976; p=0.014). Persistent statin therapy was not associated with increased time to primary outcome in either univariate or multivariable analysis among patients with low baseline CV risk.
Persistent statin therapy after a reported adverse reaction to a statin was associated with longer time to CV event or death in patients at high but not low CV risk.