bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of Life Impact in Patients with Cutaneous Toxicities Caused by Epidermal Growth Factor Receptor Inhibitors and Immunotherapy
Authors: Mannino Maria , Sollena Pietro , Di Stefani Alessandro , Rossi Ernesto , D’Argento Ettore , Schinzari Giovanni , Tortora Giampaolo , Peris Ketty
Published: April 2024

Background: Novel oncologic therapies, including epidermal growth factor receptor inhibitors (EGFR-Is) and immune checkpoint inhibitors (ICIs), are associated with a new spectrum of adverse reactions, with prominent cutaneous toxicities. The impact of cutaneous adverse events (cAEs) on patients’ quality of life (QoL) represents an unmet clinical need. Objectives: The aims of this study were (1) to assess whether cutaneous toxicities directed therapies are effective in reducing the QoL burden via the submission of 2 patient reported outcome measures (PROMs); (2) to investigate whether class of oncologic therapy, type of cAE and toxicity severity differently impact on patients’ QoL. Methods: A prospective observational study was conducted at the Dermatology department of the Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy, from October 2018 to October 2019. Patients aged ≥18 years, under therapy with EGFR-Is or ICIs and experiencing a treatment-related cAE were eligible for the study. Dermatology Life Quality Index (DLQI) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 version 3.0 (EORTC QLQ-C30) were administered to patients at first clinical visit (T0), at 1-month (T1), and at 3-month (T2) dermatological follow-up. Results: Sixty cAEs of 51 patients have been recorded. A significant difference in the mean score for both DLQI and EORTC QLQ-C30 was found along the 3-months dermatological follow-up (p < 0.0001). A similar QoL improvement was reported for PROMs stratified by class of therapy and toxicity severity (p < 0.0001). No difference was reported for patients with pyogenic granuloma-like lesions and psoriasiform eruption as per DLQI. Class of therapy and toxicity severity did not differently impact on patients’ QoL at selected timepoints; we reported a higher EORTC QLQ-C30 score at T2 for patients developing psoriasiform eruption compared to other types of cAEs. Conclusions: Early patients’ referral to dermatologists and tailored management could result in better QoL.
Effect of Maternal Age and Body Mass Index on Induction of Labor Using Oral Misoprostol in Late-Term Pregnancies: A Retrospective Cross-Sectional Study
Authors: Etrusco Andrea , Sfregola Gianfranco , Zendoli Federica , Musicco Alessandra , Belpiede Antonio , Della Pietà Cosimo , Giannini Andrea , Mikuš Mislav , Venezia Renato , Garzon Simone , Uccella Stefano , Laganà Antonio Simone
Published: April 2024

Introduction: Several studies have shown that late- and post-term pregnancies are associated with an increased risk of perinatal morbidity and mortality. In this case, induction of labor is the recommended approach. For full-term pregnancies, various methods exist to prepare the cervix and/or commence labor. Prostaglandins serve the dual purpose of cervical ripening and labor induction, blurring the distinction between the two processes. The aim of this research was to evaluate the effect of maternal age and body mass index (BMI) on oral misoprostol induction of labor for late-term pregnancies. Methods: This was a retrospective cross-sectional study (ClinicalTrial ID: NCT06184139), including only late-term pregnancies in healthy nulliparous women carrying a single cephalic fetus with normal birthweight who underwent induction of labor with oral misoprostol. We used the oral misoprostol regimen proposed by the World Health Organization (WHO) for induction of labor in term singleton pregnancies in women who have not had a previous cesarean delivery and a Bishop score <7. The regimen was oral misoprostol in aqueous solution at the low dose of 25 μg every 2 h until a Bishop score ≥7, labor, or for a maximum of 8 doses. Results: One hundred and four pregnant women underwent induction of labor with oral misoprostol for late-term pregnancy on the 290th day of gestation. Study population was divided in two groups based on age (<35 and ≥35 years) and obesity (BMI <30 and ≥30). No statistically significant differences were recorded between younger and older women. Obese women reported a longer time between the last dose of misoprostol and cervical dilation of 6 cm (p = 0.01), a longer time between the last dose of misoprostol and delivery (p = 0.04), and a higher rate of grade II vaginal lacerations (p = 0.02). Conclusions: Maternal BMI is a factor negatively influencing the efficacy of oral misoprostol for induction of labor in late-term pregnancy.
Posterior Reversible Encephalopathy Syndrome in Eclamptic Patients: The Relationship between Blood Pressure, Cranial Involvement, and Seizure Recurrence
Authors: Temel Musa , Durmuş Merve , Durmaz Şeyma Eroğlu , Güvenir Deniz , Gürkaş Erdem
Published: April 2024

Objectives: Posterior reversible encephalopathy syndrome (PRES) is a clinic radiological disorder characterized by headache, epileptic seizure, encephalopathy, visual impairment, and focal neurological deficits. Gestational hypertension, which is a significant risk factor for PRES, may cause significant morbidity and mortality among pregnant women. Design: Twenty-four patients with PRES caused by eclampsia who were admitted to our hospital in the last 5 years were included in this study. Participants/Materials, Setting, Methods: Blood pressure at admission, the number of regions with vasogenic edema in the brain, and recurrent seizures were noted. Patients were divided into three groups: mild, moderate, and severe. Results: Using Kruskal-Wallis and Pearson χ2 tests, there was no statistical significance between the groups in terms of cranial involvement (p = 0.471). However, binary logistic regression analysis showed that seizure recurrence increased in correlation with blood pressure (p = 0.04). Limitations: PRES is a rare syndrome associated with several etiologies. In our study, only patients with PRES due to eclampsia were included. Therefore, the number of included patients was limited (24 participants). Conclusion: PRES may occur in eclamptic patients with mild, moderate, or severe blood pressure values. Evaluation by magnetic resonance imaging is needed to confirm the diagnosis. Early and rapid treatment is essential for reducing morbidity and mortality among pregnant women.
Effectiveness of the Therapeutic Lifestyle Change Diet Intervention to Improve Biochemical Markers of Cardiovascular Diseases in HIV-Infected Patients with Dyslipidemia
Authors: Singhato Alongkote , Booranasuksakul Uraiporn , Khongkhon Somjet , Rueangsri Narisa
Published: April 2024

Introduction: This randomized controlled trial study aimed to investigate the effectiveness of therapeutic lifestyle change (TLC) diet intervention by the registered dietitians. Methods: Eighty-two people living with HIV (PLHIV) with dyslipidemia were randomly allocated to the intervention group as well as another 82 PLHIV with dyslipidemia to the control group. Participants in the intervention group were instructed to meet the registered dietitians every 2 weeks at weeks 0, 2, 4, 6, and 12 (a totally of 12 weeks) to receive individual medical nutrition therapy according to the TLC diet principles, while the participants in the control group only received routine health care service. Results: Triglycerides, total cholesterol, and LDL cholesterol of the intervention group were significantly lower than those of the control group at the endpoint (p < 0.05). In addition, these biomarkers and C-reactive protein of the intervention group were significantly lower when compared with their baseline (p < 0.05). The overall dietary habits of participants in the intervention group were significantly improved at the end of the study (p < 0.05). Conclusion: The medical nutrition therapy intervention based on the TLC diet is effective in improving blood lipid profiles among PLHIV with dyslipidemia.
High Doses of Caffeine-Induced Cerebral Infarction Leading to Partial Locked-In Syndrome in a Young Adult: A Novel Association?
Authors: Sinha Vijay , Lam Loc , Nguyen Michael
Published: April 2024

This is a case of a 30-year-old male with no prior medical conditions presented to the emergency department for presumed seizures after ingesting 900 mg of caffeine via pre-workout drinks and pills. Patient was described as having nearly 15 minutes of generalized seizure activity observed by emergency medical service, requiring midazolam. A head computerized tomography (CT) demonstrated a possible thrombus, and further, CT angiography and CT perfusion confirmed a basilar artery occlusion. He was treated with tissue plasminogen activator (tPA) and underwent thrombectomy achieving TICI grade 3 in the left posterior cerebral artery and TICI grade 2b in the superior cerebellar artery. Unfortunately, the patient experienced a hemorrhagic conversion leading to an incomplete locked-in syndrome. This case report suggests a novel association between energy drinks and caffeine supplements as potential etiologies for rapid onset on cerebrovascular incidents.
Notas sobre Felidos neotropicales. III. Contribución al conocimiento de Felis geoffroyi D'Orbigny e Gervais, 1844 y sus formas geográficas (Mammalia, Felidae)
Authors: Ximenez Alfredo
Published: April 2024

.
Herpetofauna das dunas interiores do Rio São Francisco, Bahia, Brasil. II. Psilophthalmus: um novo gênero de Microteiidae sem Palpebra (Sauria, Teiidae).
Authors: Rodrigues Miguel Trefaut
Published: April 2024

.
Revisão das espécies da Família Batrachoididae do litoral brasileiro com a descrição de uma espécie nova (Osteichthyes, Teleostei, Batrachoidiformes)
Authors: Menezes Naércio A. , Figueiredo José Lima de
Published: April 2024

.
Abstract 4195: High-Dose Atorvastatin Therapy Can Completely Reverse Monocyte Dysfunction in Hypercholesterolemic Patients with Coronary Artery Disease
Authors: Czepluch Frauke S , Waltenberger Johannes
Published: April 2024

Statins, a key component in the primary and secondary CAD prevention, reduce cardiovascular events even in normo- and hypocholesterolemic individuals. Intact monocyte function is crucial for collateral artery development. In the presence of hypercholesterolemia (HC), collateral formation is severely impaired. We could previously show that MCP-1-induced monocyte chemotaxis is significantly decreased in hypercholesterolemic CAD patients. Therefore, we investigated whether a therapy with atorvastatin 40 mg once a day could improve monocyte function in CAD patients with HC, and whether this influences MCP-1 plasma levels. Fifty CAD patients with HC as a single cardiovascular risk factor were randomized to receive either atorvastatin 40 mg or a placebo once daily for 4 weeks. Monocytes were isolated from peripheral blood. Their migratory responsiveness towards MCP-1 (10 ng/ml) was assessed in a micro-chemotaxis chamber before and at the end of the study. MCP-1 plasma levels were analyzed using ELISA. Before starting study medication, monocyte chemotaxis towards MCP-1 did not differ between the atorvastatin group and the placebo group (122% vs. 114%; p=NS). After 4 weeks, the migratory response of monocytes from atorvastatin-treated patients significantly improved, whereas the monocytes from placebo-treated patients showed a further decline in function (149% vs. 109%; p<0.001). A significant negative correlation existed between LDL-C levels and MCP-1-induced monocyte chemotaxis (p<0.001). With regard to MCP-1 plasma levels, there was no significant difference in CAD patients treated with or without atorvastatin (476 vs. 671 pg/ml; p=NS) for 4 weeks.Based on our data, a high-dose atorvastatin therapy can completely reverse the negative influence of HC on monocyte function, whereas monocyte chemotaxis further decreases in the absence of any lipid-lowering therapy. The migratory responsiveness of monocytes is closely associated with LDL-levels indicating that statin effects on monocytes are rather cholesterol-dependent than pleiotropic. High-dose statin therapy might be regarded as an important contribution to primary and secondary prevention in CAD by improving the patients’ ability to form functional coronary collaterals.
Abstract 4202: Migraine is Associated with Increased Risk of Cardiovascular Disease in Men
Authors: Kurth Tobias , Gaziano J. Michael , Cook Nancy R , Bubew Vadim , Logroscino Giancarlo , Diener Hans-Christoph , Buring Julie E
Published: April 2024

Background:
The vascular component of the migraine-specific physiology and an observed adverse cardiovascular risk profile among migraineurs suggest an association between migraine and cardiovascular disease (CVD). In women, migraine has recently been associated with increased risk of CVD, including coronary events. Compatible data in men are lacking.

Objectives:
To evaluate the association between migraine and subsequent CVD as well as specific CVD events in apparently healthy men.

Methods:
Prospective cohort study among 20,084 men participating in the Physicians’ Health Study. In yearly questionnaires, men were asked for information on migraine, risk factors, and the occurrence of study endpoints. We classified men as having migraine if they indicated migraine during the first 60 months, after which follow-up began. Information on aura was not available. All men were free of outcome events at start of follow-up. During 15.7 years, we followed participants for the occurrence of a first major CVD event (nonfatal ischemic stroke, nonfatal myocardial infarction, or death from ischemic CVD). We also evaluated the individual endpoints as well as coronary revascularization and angina.

Results:
A total of 1449 (7.2%) men reported migraine and during follow-up 2236 major CVD events occurred. Compared to non-migraineurs, men who reported migraine had multivariable-adjusted hazard ratios (95% confidence intervals) of 1.24 (1.06–1.46; P=0.008) for major CVD, 1.12 (0.84–1.50; P=0.43) for ischemic stroke, 1.42 (1.15–1.77; P<0.001) for myocardial infarction, 1.05 (0.89–1.24; P=0.54) for coronary revascularization, 1.15 (0.99–1.33; P=0.068) for angina, and 1.07 (0.80–1.43; P=0.65) for ischemic cardiovascular death.

Conclusions:
In this large prospective cohort of apparently healthy men, migraine was associated with increased risk of major CVD, which was driven by the increased risk of myocardial infarction.
Abstract 590: Abrogation of Nuclear Factor-Kappa B Activation in the Heart Alleviates Post-Infarction LV Remodeling
Authors: Hamid Tariq , Xiang Xilin , Marshall James P , Cardwell Ernest , Wang Guangwu , Dawn Buddhadeb , Prabhu Sumanth D
Published: April 2024

The failing heart is characterized by chronic activation of nuclear factor (NF)-κB, a central transcriptional mediator of inflammatory and stress responses. As NF-κB can signal to either survival or apoptotic pathways, however, whether such activation confers cardioprotective or detrimental effects is unknown. We tested the
hypothesis
that sustained activation of NF-κB exacerbates LV remodeling in heart failure (HF). We examined LV remodeling following permanent coronary ligation (or sham-operation) in adult male transgenic (TG) mice with NF-κB abrogation in the heart via the cardiac-specific overexpression of a phosphorylation-resistant IκBα (n=16), or in non-transgenic (NTG) littermates (n=16). Baseline echocardiography showed no inherent cardiac phenotype in the TG mice. Compared to NTG sham, 4 weeks after surgery, NTG HF hearts showed:

increased (p < 0.01) LV size (EDV 94 ± 35 vs. 35 ± 5 μL) and systolic dysfunction (LVEF 50 ± 9 vs. 75 ± 7 %) by echocardiography;

hypertrophy (LV/tibia length [TL] 5.3 ± 0.7 vs. 3.7 ± 0.3, p < 0.001; ~2-fold greater atrial natriuretic factor [ANF] mRNA, p < 0.05);

significantly (p < 0.05) increased (~2-fold) NF-κB DNA binding activity and mRNA levels of the NF-κB-responsive cytokines tumor necrosis factor (TNF), interleukin (IL)-1β, and IL-6; and

increased apoptotic rates by TUNEL staining (1.1 ± 0.5 vs. 0.03 ± 0.03%, p < 0.05).

In contrast, compared to NTG HF, TG HF hearts had markedly reduced (p < 0.01) NF-κB DNA activation, and significantly less (p < 0.05) LV dilatation (LVEDV 52 ± 20 μL) and systolic dysfunction (LVEF 61 ± 8 %), but a similar degree of hypertrophy as assessed by LV/TL and ANF expression. Moreover, as compared to TG sham, TG HF hearts exhibited no TNF, IL-1β, or IL-6 upregulation. Importantly, as compared to TG sham, TG HF showed only a mild increase in apoptotic rate (0.4 ± 0.3 %) that was not statistically significant (p = 0.45), suggesting that differences in the rate of cell loss between NTG and TG HF may account for comparable degrees of chamber hypertrophy despite differences in LV dilatation.

Conclusion:
Persistent NF-κB activation imparts detrimental effects in post-infarction HF and worsens LV remodeling, related, at least in part, to augmentation of inflammatory cytokine expression and apoptosis.
2006 Helen B. Taussig Memorial Lecture—Plato, Epistemology, and Cardiology, or, Should Doctors Think Like Lawyers?
Authors: Driscoll David
Published: April 2024

Mistakes occur because doctors make diagnoses and therapeutic decisions on the basis of what they think is correct knowledge but is, in fact, incorrect knowledge. Attainment of knowledge relies on sense experience, and sense experience can be misleading. Medical tests are interfaces between patients and doctors, and sense experiences are distorted by these interfaces. Knowledge can be attained by “reasoning.” Deductive reasoning, utilizing a properly constructed syllogism, is the only way one attains knowledge with 100% certainty. Knowledge attained by all other methods is only correct with a probability <100%. In addition to reasoning, one can gain knowledge on the basis of appeals to authority (eg, expert witness), experience, intuition, revelation, and faith. The level of certainty of knowledge that one can achieve is related to the method used to achieve that knowledge; deductive reasoning is more reliable, for example, than intuition, revelation, or faith. Doctors and lawyers must determine what is true or correct about matters that are uncertain or contingent. Doctors, like lawyers, deal with evidence (medical history and test results). To avoid errors, doctors must treat evidence with the same level of skepticism that lawyers do. Doctors must be aware of what constitutes quality of evidence. If they are not, medical errors will result. In summary, doctors must understand the basic principles of epistemology. Doctors never deal with 100% certain knowledge and hence must rely upon “wisdom,” which is the ability to make the right decision in the absence of certain knowledge.
2006 James B. Herrick Award and Lecture—Drug-Eluting Stents: The Beginning of the End or the End of the Beginning?
Authors: Serruys Patrick
Published: April 2024

In 2003–2004, drug-eluting stents (DES) were approved by regulatory bodies in the European Union and United States. Pivotal studies in the preceding year had demonstrated a major treatment effect (60% to 80%) on angiographic restenosis irrespective of the type of lesion or clinical syndrome. Interventional cardiologists worldwide swiftly embraced this new modality of treatment, with market penetration of 30% to 90%. This disruptive technology—without evidence base— has already had a major impact on our approach to coronary revascularization. Patients traditionally referred for surgery are now revascularized percutaneously. But in 2008–2009, results of major trials comparing percutaneous coronary intervention with coronary artery bypass grafting (SYNTAX, FREEDOM, COMBAT, CARDIA) in patients with 3VD and/or LMS may confirm the value of DES in “surgical” patients, and the beginning of the end of a surgical era might be on the horizon. On the other hand, worrisome information about late stent thrombosis is currently emerging. The drugs used are potent cytostatic or cytotoxic agents with long-term detrimental effects on endothelialization. Large investigator-driven registries with long follow-up suggest an unabated rate of late stent thrombosis even after 3 years. New pharmacological strategies (nonpolymeric reservoir, dual-drug elution, use of antithrombotic and antiinflammatory agents) and new absorbable metallic or nonmetallic platforms are currently being tested. The primary goal is no longer “oncologic” inhibition of neointimal hyperplasia but the restitution of a healthy and functionally active endothelial lining (eg, by capturing progenitor endothelial cells), capable—in conjunction with prohealing drugs (eg, NO donors)—of modulating the healing process without the use of permanent metallic stents. From this viewpoint, we are just at the end of the pioneering phase of the first generation of DES…and the end of the beginning.
MicroRNA-210 Controls Metabolic Adaptation During Hypoxia in Pulmonary Vascular Endothelium
Authors: Chan Stephen Y.
Published: April 2024

Abstract #3060

Stephen Y. Chan, Massachusetts General Hosp, Brigham & Women’s Hosp, Boston, MA; Ying-Yi Zhang, Brigham & Women’s Hosp, and Harvard Medical Sch, Boston, MA; Craig Hemann, Jay L. Zweier, Ohio State Univ, Columbus, OH; Joseph Loscalzo, Brigham & Women’s Hosp, and Harvard Medical Sch, Boston, MA

Stephen Y. Chan, 2009 Finalist and Presenting Author
In Vivo Kinetics of Embryonic Stem Cell Viability Following Transplantation Into the Injured Murine Myocardium
Authors: Chung Jaehoon
Published: April 2024

Abstract #250

Jaehoon Chung, Kehkooi Kee, Joelle K Barral, Rajesh Dash, Irving Weissman, Thomas Quertermous, Robert C Robbins, Dwight G Nishimura, Renee A Reijo-Pera, Phillip C Yang, Stanford University, Stanford, CA

Jaehoon Chung, 2009 Finalist and Presenting Author
Feasibility of Three Dimensional Anatomic, Dynamic and Perfusion Imaging of Myocardial Scar Using Contrast Enhanced Multi-Detector Computer Tomography to Guide Ventricular Tachycardia Ablations
Authors: Tian Jing
Published: April 2024

Abstract #252

Jing Tian, Jean Jeudy, Mark Smith, Peng Lei, Univ of Maryland Sch of Med, Baltimore, MD; Aharon Turgeman, Aharon Abbo, Biosense Webster Inc., Tirat Carmel, Israel; Robert Peters, Magdi Saba, Stephen Shorofsky, Timm Dickfeld, Univ of Maryland Sch of Med, Baltimore, MD

Jing Tian, 2009 Finalist and Presenting Author
Development and Testing a Dynamic Bi-leaflet Mitral Prosthesis
Authors: Kheradvar Arash
Published: April 2024

Abstract #4223

Arash Kheradvar, Univ of South Carolina, Columbia, SC

Arash Kheradvar, 2009 Finalist and Presenting Author
Abstract 4754: Determining the Optimal Cross-sectional Analysis Interval for OCT Assessment of Coronary Stenting
Authors: Bezerra Hiram G , Guagliumi Giulio , Kyono Hiroyuki , Tahara Satoko , Rosenthal Noah , Musumeci Giuseppe , Sirbu Vasile , Valsecchi Orazio , Aprile Alessandro , Simon Daniel , Costa Marco A
Published: April 2024

Introduction:
Intracoronary Optical Coherence Tomography (OCT) provides high resolution images and allows detailed stent strut level analysis (SLA). SLA was proposed recently as a surrogate endpoint for DES safety. We aim to define the “optimal” sampling interval for SLA: combining minimal data variability with optimal post-processing time of analysis.

Methods:
A total of 14.716 cross-sections from 192 patients and 4 different stents type (Endeavor, Taxus, Cypher and Liberte (BMS)) were studied. A total of 456 stent segments were analyzed. Data sampling every five frames (0.3 mm) for cross-sectional area (0.06mm) for SLA were considered the reference method. Data sampling at increments 5 frames for area measurement and 1 frame for percentage of strut coverage were compared with the reference interval to define variability. Variability was calculated as absolute difference from the reference method at different analysis interval.

Results:
A low variability (<10%) was observed for minimal lumen and stent area measurements for all tested interval analyses. At the maximum tested interval (40 frames, 2.4 mm) the variability (%, SD) for minimal lumen and stent area was 9.6±16.2, 5.8±6, respectively. Detection of any uncovered struts showed good agreement (Kappa>0.8) up to every-7-frame SLA sampling (0.42 mm intervals). However, the variability for percentage of uncovered struts was high even at the lowest (every 2 frames) analysis interval (11.7±25) and reached unacceptable 51.9±132 at 15 frames (~1 mm) analysis interval.

Conclusion:
Lumen and stent area measurements by OCT showed low variability in all tested analysis intervals. However, percentage of uncovered struts has high variability even at high data sampling. The ideal cross-section data sampling for OCT stent analysis is highly dependent on the variable of interest.

Variability related with the analysis interval
Abstract 4757: Attenuated Plaque Identified by Intravascular Ultrasound Predicts No-Reflow After Stenting in Acute Myocardial Infarction: The HORIZONS-AMI Trial
Authors: Wu Xiaofan , Maehara Akiko , Mintz Gary S , Lansky Alexandra J , Witzenbichler Bernhard , Guagliumi Giulio , Brodie Bruce , Kellett Mirle A , Parise Helen , Mehran Roxana , Stone Gregg W
Published: April 2024

Background:

Observational studies have suggested that attenuated plaques identified by grayscale intravascular ultrasound (IVUS) may predict transient deterioration in flow during percutaneous coronary intervention (PCI). If so, this phenomenon would be expected to be noted in pts undergoing primary PCI for STEMI.

Methods and Results:

We analyzed clinical, angiographic and IVUS characteristics of infarct related arteries of 365 stented pts from the randomized HORIZONS-AMI trial. No-reflow was defined as final TIMI grade 0, 1 or 2 flow in the absence of a mechanical obstruction on the post-PCI angiogram. Attenuated plaque was defined as hypoechoic or mixed atheroma with ultrasound attenuation without calcification. A mean attenuation score was created by measuring the angle of attenuation each 1mm, scoring as 1, 2, 3, or 4 when the angle was <90°, 90 –180°, 180–270°, or 270–360°, respectively, then summing the scores and normalizing for analysis length. 77.8% pts had attenuated plaques, and no-reflow occurred in 10.1%. Pts with no-reflow more often had PCI of a LAD than non LAD (59.5% vs 36.9%,
P
=0.03) and had a higher mean attenuation score (median [95%CI]=2.2 [0, 2.8] vs 1.3 [0.6, 1.8], P<0.001). There were no differences in baseline thrombus area, IVUS plaque burden, echolucent plaque, and stent expansion between pts with vs without no-reflow. The mean attenuation score that best predicted no-reflow was ≥2 (90–180°), with a sensitivity of 81.5% and a specificity of 80.5%.

Conclusions:

Attenuated plaque is present in three-quarters of pts with AMI, PCI of which is strongly correlated with no reflow. The larger the attenuated plaque, the greater the likelihood of no-reflow.

Figure

Attenuation angle: 125°

Attenuation score: 2 points
Abstract 4859: Genetic Polymorphism T45G on Adiponectin Gene Affects Cardiovascular Risk by Regulating Adiponectin Levels in Arterial Hypertension
Authors: Antonopoulos Alexis S , Tousoulis Dimitris , Antoniades Charalambos , Miliou Antigoni , Koumallos Nikolaos , Hatzis George , Demosthenous Michalis , Bakogiannis Constantinos , Stefanadi Elli , Tsioufis Costas , Papageorgiou Nikolaos , Siasos Gerasimos , Ntarladimas Ioannis , Stefanadis Christodoulos
Published: April 2024

Background: Evidence suggests that adiponectin, an adipokine facilitating insulin action, has antiatherogenic effects, while it is inversely associated with obesity and the development of arterial hypertension. We examined the impact of T45G polymorphism on adiponectin gene, on the risk for coronary artery disease (CAD) and the expression of adipokines in heathy individuals and patients with CAD. We also examined its possible impact on the development of arterial hypertension.

Methods: We studied 214 pts with CAD and 147 healthy controls. Genetic polymorphism T45G was determined by PCR, while circulating adiponectin, resistin and leptin were determined by ELISA, under stable clinical conditions.

Results: The genotype distribution was different between CAD patients (GG: 5(2.3%) GT: 65(30.4%), TT:144(67.3%)) and controls (GG:2(1.4%), GT: 31(21.1%), TT:114(77.6%), p<0.05). The risk for CAD was OR[95%CI]:0.595[0.368 – 0.964], p=0.03 for 45TT vs 45GT+GG. Importantly, The 45TT homozygotes had lower risk of arterial hypertension (OR[95%CI]:0.439[0.270 – 0.713], p=0.001). The 45TT genotype was associated with higher adiponectin levels (13.1±1.14pg/ml) compared to 45GT+GG (8.30±2.17pg/ml, p<0.05) among healthy individuals, but not in CAD patients (13.67±0.97 vs 15.20±1.6pg/ml respectively, p=NS). Circulating resistin and leptin were not different between genotypes in the control group (6.88±0.40 and 13.6±0.85 in TT vs 6.16±0.65 pg/ml and 14.04±2.23 pg/ml in GT+GG, p=NS for both). In the CAD group, leptin levels were also similar between 45TT (15.2±1.8pg/ml) and 45GT+GG (14.1±3.2pg/ml, p=NS). Similarly, the 45TT genotype had similar resistin (5.9±0.3pg/ml) compared to 45GT+GG (7.69±0.81pg/ml, p=NS), in the CAD group.

Conclusions: The 45TT genotype of adiponectin gene is associated with lower risk of arterial hypertension and decreased cardiovascular risk. This genotype has a striking effect on adiponectin expression in healthy individuals, but not in CAD patients. Therefore, homozygosity for the 45T allele decreases the risk for CAD by increasing circulating levels of adiponectin in healthy individuals, while its functional effect is masked after the establishment of coronary atherosclerosis.
Abstract 4888: A Novel Role of Kruppel-like Factor 2 (KLF2) in Regulating Endothelial Barrier Function
Authors: Lin Zhiyong , Natesan Viswanath , Shi Hong , Kawanami Daiji , Hao Caili , Mahabaleshwar Ganapati H , Atkins G. Brandon , Finigan James H , Jain Mukesh K
Published: April 2024

Background
: Selective permeability is a life sustaining function of endothelial cells. Defects in permeability are implicated in several diseases such as sepsis, ischemia reperfusion injury and diabetes. Previous studies by our group and others have identified KLF2 as a molecular switch regulating endothelial gene expression and function. However the role of KLF2 in vascular permeability remains unknown.

Methods and Results
: Adenoviral overexpression of KLF2 in HUVECs strongly attenuated the increase of endothelial permeability by thrombin (1U/ml), histamine (200
μ
M) and hydrogen peroxide (500
μ
M) as measured by two independent assays – transendothelial electrical resistance (TER) and FITC-Dextran passage using a transwell system. Conversely, KLF2 deficiency in HUVECs (by siRNA knockdown) and primary mouse endothelial cells (derived from KLF2 +/+ and KLF2+/− mice) exhibited a marked increase in thrombin-induced permeability. To assess the effect of KLF2 in vascular permeability
in vivo,
we measured the leakage of Evans Blue dye into interstitial tissues of the mouse ear (expressed as
μ
g of dye/mg of ear tissue) after treatment with mustard oil. Consistent with our
in vitro
observation, by comparison to KLF2+/+ mice, KLF2 +/− mice exhibited a significantly higher degree of vascular leak (53.4±2.68
μ
g/mg in KLF2+/+ versus 72.36±4.71
μ
g/mg in KLF2+/−, p<0.05). Mechanistically, our gain and loss-of-function studies indicate that KLF2 differentially affects key endothelial targets that regulate barrier function. Specifically, KLF2

markedly attenuated agonist- induced increase in Myosin Light Chain (MLC) phosphorylation (a key signaling molecule that promotes endothelial barrier permeability),

increased Rac1 activation (a small GTPase that has been shown to confer barrier protection properties), and

increased the expression of occludin and zona occludens-1 (tight junction proteins that promote barrier function).

Conclusions
: These observations identify KLF2 as an essential regulator of endothelial barrier function. Targeting of KLF2 function may be beneficial in disorders characterized by excessive vascular permeability such as sepsis.

This research has received full or partial funding support from the American Heart Association, Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).
Abstract 4911: miR-200c is Up-regulated by Oxidative Stress and Induces Endothelial Cell Apoptosis and Senescence
Authors: Magenta Alessandra , Ferraris Gianluca Sarra , Martelli Fabio , Capogrossi Maurizio C
Published: April 2024

Background.
microRNAs (miR) are small non-coding RNAs that inhibit translation of messenger RNAs (mRNA) into proteins and play a key role in the modulation of cell function. The objective of this work was to examine the effect of oxidative stress on human umbilical vein endothelial cells (HUVEC) miR expression.

Methods and results.
HUVEC were exposed to 200
μ
M H
2
O
2
for 8 to 24 hours; out of 254 miRNAs examined only 2 increased > 8-fold, miR-200c (28.30 ± 8.8 fold
vs
control; p < 0.01) and the co-transcribed miR-141(26.72 ± 10.23 fold
vs
control; p < 0.02); peak expression was achieved after 16 hours exposure to oxidative stress. All other members of the miR-8 gene family to which miR-200c and miR-141 belong, i.e. miR429, miR200a and miR200b were induced by H
2
O
2
, albeit to a lower level: i.e. 4 – 8 fold increase. This response to oxidative stress was not limited to HUVEC since a similar increase in miR-200c was also found in C2C12 cells growing or differentiated in myotubes exposed to H
2
O
2
. Further, oxidative stress induced with 0.25 mM BCNU also up-regulated miR-200c (3.18 ± 0.96 fold; p < 0.02) and this response was prevented by pre-incubation with the free radical scavenger NAC (10 mM). Over-expression of miR-200c in HUVEC induced cell growth arrest, enhanced apoptosis (3.36 ± 1.05 fold
vs
control; p < 0.01) and induced cellular senescence as indicated by positive beta-galactosidase (
β
-gal)staining (scramble miR:12.66% ± 2.27
β
-gal positive cells; miR-200c: 87.36%± 4.85
β
-gal positive cells); all these effects on cell proliferation, apoptosis and senescence are known to be caused by oxidative stress. ZEB1 is a well-known target of miR-200c and lack of ZEB1 has been linked to an enhanced cellular senescence. It was found that under our experimental conditions in HUVEC exposed to H
2
O
2
both ZEB1 mRNA and protein decreased and the over-expression of miR-200c in HUVEC down-regulates ZEB1 mRNA and protein.

Conclusions.
Oxidative stress markedly increases miR-200c and its family members and down-regulates ZEB1, which is a known miR-200c target. Further, the over-expression of miR-200c induces cell growth arrest, enhances apoptosis and induces cell senescence. Thus, miR-200c may play a key role in mediating the effect of oxidative stress on cell function and survival.
Abstract 4932: CXCR4 Expression on Bone Marrow-derived Cells Was Regulated Positively by Calcium and Negatively by Aging
Authors: Xu Qiyuan , Wu Qiuling , Shao Hongwei , Li Jiahui , Ma Qi , Eton Darwin , Webster Keith A , Yu Hong
Published: April 2024

Cell surface receptors play major roles in the mobilization and homing of progenitor cells from the bone marrow to peripheral tissues. CXCR4 is an important receptor that regulates homing of leukocytes and vascular progenitor cells (VPC) in response to the chemokine stromal cell-derived factor-1 (SDF-1). Ionic calcium is also known to regulate chemotaxis of selective bone marrow-derived cells (BMC) through the calcium-sensing receptor CaR. We assessed the hypothesis that calcium regulates CXCR4 expression on BMC; defective CXCR4 expression develops with aging, which results in less VPC homing to vascular lesion site and inefficient repair. We found that CXCR4 surface expression is age-dependent. CXCR4 on the surface of BMC from old mice (24 months old) is significantly lower than young mice. We also found that CaCl
2
treatment of BMC from young mice induced a significant increase in both the transcription and cell surface expression of CXCR4. BMC subpopulations expressing VEGFR2
+
and CD34
+
, which were considered as endothelial progenitor cells, were especially sensitive to calcium. The effects were blocked by calcium influx inhibitors, anti-CaR antibody, and the protein synthesis inhibitor cycloheximide. Calcium treatment also enhanced SDF-1-mediated CXCR4 internalization. These changes were reflected in significantly improved chemotaxis by SDF-1, which was abolished by the CXCR4 antagonist AMD3100 and by antibody against CXCR4. Calcium pre-treatment improved homing of CD34
+
BMC to ischemic muscle in vivo, and enhanced revascularization in ischemic mouse hindlimbs. Such calcium-mediated increase of surface CXCR4 was not observed on BMC from old mice. Pre-treatment of BMC from old mice with calcium did not significantly improve the cellular signaling response to SDF-1, nor enhance homing of injected BMC to ischemic muscle and blood reperfusion in vivo. In conclusion, we identified calcium as a positive regulator of CXCR4 expression that enhances progenitor cell mobility and efficiency of cell-based therapy. Aging negatively affects BMC CXCR4 expression and its interaction with SDF-1.

This research has received full or partial funding support from the American Heart Association, Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico & Tennessee).
Abstract 5009: Prothrombotic Effect After Aspirin Discontinuation is Cox 2-dependent
Authors: Doutremepuich Christian , Aguejouf Omar M , Desplat Vanessa L , Eizayaga Francisco X
Published: April 2024

Aspirin (ASA) discontinuation for surgery or non-compliance increases the risk of a thrombotic accident or stent thrombosis, especially after the second week. Previous papers have shown that 8 to 10 days after a single high dose of ASA in the rat, a pro-thrombotic state develops. We hypothesized that insignificant amounts of ASA may remain after discontinuation and cause a prothrombotic COX 2-mediated effect.

Mehtods: Wistar rats (1000) were separated into 100 groups. Induced hemorrhagic time in seconds (IHT) and Laser-induced thrombosis, expressed as number of emboli (NE), were used. ASA was injected in 100 mg/kg, 1 mg/kg or 1/100 dilutions (Dil) 5, 9 or 15, subcutaneously, in a final volume of 1 ml/kg. Sterilized water was used as placebo. Selective inhibitors of COX 1 (SC-560) or COX 2 (NS-398) were used at 2.5, 5, 7.5 and 10 mg/kg, intragastrically. Carboxy-methyl-cellulose, the vehicle of COX inhibitors, was used as control. Each group was compared with its control with the t-test, p<0.05 was considered significant.

Results: (only highest or lowest doses shown) the highest dose of ASA prolonged IHT and decreased thrombosis. A clear opposite trend was observed with the highest dilution, which generated a shortened IHT and an increased NE. SC-560 produced an effect similar to the higher doses of ASA, prolonged IHT and decreased NE, proportional to dose increase. This effect of COX 1 inhibition was antagonized by the highest ASA dilutions. NS-398 created a pro-thrombotic effect that was antagonized by ASA at higher doses. There was no further effect of the highest dilution of ASA after NS-398.

Conclusion: There is a clear prothrombotic effect of ASA Dil 15 that is opposed to COX 1 inhibition and which is inhibited by COX 2 inhibition. COX 2 inhibition and Dil 15 of ASA have similar effects. The prothrombotic effect of the highest dilution of ASA is achieved through COX 2 inhibition and may be blamed for the thrombotic accidents and stent thrombosis described after ASA discontinuation.
Abstract 5043: Telmisartan Enhances Mitochondrial Biogenesis and Protects From Endothelial Cell Damage Through Peroxisome Proliferator-Activated Receptor-
γ
Independent Pathways
Authors: Nozaki Toshimitsu , Sugiyama Seigo , Sugamura Koichi , Ogawa Hisao
Published: April 2024

Background
Mitochondrial dysfunction in endothelial cells (EC) might be involved in atherogenesis. Telmisartan (TELMI), which has peroxisome proliferator-activated receptor (PPAR)-
γ
activating properties, has been shown to reduce cardiovascular events in high risk patients. We investigated whether TELMI could modulate mitochondrial function in human coronary artery endothelial cells (HCAEC).

Methods and Results
Pretreatment of HCAEC with 10
μ
M TELMI preserved the mitochondrial function from H
2
O
2
exposure (1.0mM, 60min) evaluated by mitochondrial nicotinamide adenine dinucleotide (NADH) levels (NADH: 1.3±0.2 fold greater than vehicle, n=6, p<0.01), and also reduced apoptotic annexin V positive EC induced by H
2
O
2
(100
μ
M, 30min) (% apoptosis EC: vehicle 38.3±3.1%, TELMI 26.0±2.3, n=6, p<0.01). TELMI increased EC mitochondrial number as assessed by fluorescence intensity of MitoTracker Green (vehicle 17.5±0.7, TELMI 21.3±2.1, n=6, p<0.01) and enhanced EC mitochondrial function as assessed by colorimetric NADH assay, in a time and concentration dependent manner (0–48 hours, 0.1–10
μ
M, up to 1.9±0.1 fold, n=7, p<0.01), but other sartans did not have the similar effects. In senescent HCAEC at the 16
th
passage, TELMI inhibited the appearance of giant EC (vehicle 44.3±5.2/field; TELMI 0.8±1.0, n=6, p<0.01). TELMI treatment significantly enhanced EC tube formation (tube length: 4.1±0.4 fold greater than vehicle, n=5, p<0.01), and we observed significant increases in mRNA expression levels of eNOS, VEGFA, mitochondrial transcription factor A, and Sirt1 in HCAEC after 48 hours TELMI treatment (1.3±0.2, 2.0±0.5, 1.2±0.04, 1.3±0.2 fold, respectively, all p<0.05). To determine the possible involvement of PPAR
γ
pathway, we knocked down PPAR
γ
with siRNA and inhibited PPAR
γ
-mediated signaling by selective PPAR
γ
blockers; GW9662 and T0070907. These two strategies did not affect the increased mitochondrial NADH levels induced by TELMI. Consistently, GW1929, a selective PPAR
γ
agonist, did not alter mitochondrial function in HCAEC.

Conclusion
TELMI upregulates mitochondrial function in human EC through PPAR
γ
independent signaling mechanisms. TELMI could exhibit anti-atherogenic effects through improving mitochondrial dysfunction in EC.
Abstract 5046: Nitric Oxide and Superoxide Dismutase Modulate Endothelial Progenitor Cell Function in Type 2 Diabetes Mellitus
Authors: Hamed Saher , Brenner Benjamin , Roguin Ariel
Published: April 2024

Objectives:
To investigate the roles of NO and SOD in glucose-stressed endothelial progenitor cells (EPCs).

Background:
The function of EPCs, which are key cells in vascular repair, is impaired in diabetes mellitus (DM). Nitric oxide (NO) and reactive oxygen species can regulate EPC functions. EPCs tolerate oxidative stress by upregulating superoxide dismutase (SOD), the enzyme that neutralizes superoxide anion (O
2
−
).

Methods:
The functions of circulating EPCs from patients with type 2 DM were compared to those from healthy individuals. Healthy EPCs were glucose-stressed, and then treated with insulin and/or SOD. We assessed O
2
−
generation, NO production, SOD activity, and their ability to form colonies.

Results:
EPCs from DM patients generated more O
2
−
, had higher SOD activity, but lower NO bioavailability, than those from the healthy individuals. Serum fasting glucose and HbA1c levels in the DM patients were correlated negatively with the NO production from their EPCs. SOD treatment of glucose-stressed EPCs attenuated O
2
−
generation, restored NO production, and partially restored their ability to form colonies. Insulin treatment of glucose-stressed EPCs increased NO production, but did not change O
2
−
generation and their ability to form colonies. However, their ability to produce NO and to form colonies was fully restored after combined SOD and insulin treatment.

Conclusions:
Our data provide evidence that SOD may play an essential role in EPCs, and emphasize the important role of antioxidant therapy in type 2 DM patients.
Abstract 5111: Endothelial Neuregulin Expression is Essential for Angiogenesis in Response to Hindlimb Ischemia
Authors: Hedhli Nadia , Dobrucki Lawrence W , Kalinowski April , Wu Xiaohong , Sinusas Albert J , Russell Kerry S
Published: April 2024

Neuregulins (NRG) are a family of growth factors synthesized by endothelial cells and shown to promote cell survival and growth via activation of erbB receptors. We have previously shown that NRG/erbB signaling may play a role in angiogenesis. Here, we tested whether endothelial-specific NRG deletion in vivo would affect angiogenesis in response to hindlimb ischemia induced by femoral artery ligation. A mouse expressing tamoxifen-inducible Cre-recombinase under the control of the vascular endothelial cadherin promoter with homozygously floxed NRG sites (CFF) was generated. CFF or Cre only expressing mice (C) were treated daily with vehicle or tamoxifen beginning three days before femoral artery ligation (1 mg, ip to knock out endothelial NRG expression) and continuing for 7 days after surgery (n=5– 8 per group). To assess angiogenesis, mice were injected with a 99mTc-labeled Arg-Gly-Asp (RGD) peptide (99mTc-
NC100692
, GE Healthcare) that specifically binds to activated
α
v integrins, followed by microSPECT imaging at 60 minutes post injection. Nuclear images were analyzed and the ratio of ischemic-to-nonischemic (I/N)
NC100692
uptake within the distal hindlimb was calculated. The I/N uptake ratio was comparable between C tamoxifen and CFF vehicle treated animals (1.90±0.07 vs. 1.71±0.1, NS), but was significantly reduced in the CFF tamoxifen treated animals (1.29±0.1, P<0.05 vs. both controls), indicating a decrease in angiogenesis. These findings were further validated using anti-PECAM stained sections of muscles taken from ischemic and non-ischemic hindlimbs to quantify capillaries. The ratio of capillary numbers per muscle fiber in the ischemic to nonischemic area was comparable between the C tamoxifen and CFF vehicle (1.52±0.28 vs. 1.46±0.18, NS). However, this ratio was significantly reduced in the CFF tamoxifen treated animals (1.07±0.09, P<0.05 vs. both controls), confirming an impaired angiogenic response. These findings demonstrate a central role for NRG in mediating ischemia-induced angiogenesis and highlight the NRG/erbB pathway as a potential clinical target in the treatment of pathological and non-pathological angiogenesis.