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Aims: To describe and explore predictors of bystander defibrillation in Ireland during the period 2012 to 2020. To examine the relationship between bystander defibrillation and health system developments., Methods: National level Out of Hospital Cardiac Arrest (OHCA) registry data were interrogated, focusing on patients who had defibrillation performed. Bystander defibrillation (as compared to EMS initiated defibrillation) was the key outcome of concern. Logistic regression models were built and refined by fitting predictors, performing stepwise variable selection and by adding pairwise interactions that improved fit., Results: The data included 5,751 cases of OHCA where defibrillation was performed. Increasing year over time (OR 1.17, 95% CI 1.13, 1.21) was associated with increased adjusted odds of bystander defibrillation. Non-cardiac aetiology was associated with reduced adjusted odds of bystander defibrillation (OR 0.30, 95% CI 0.21, 0.42), as were increasing age in years (OR 0.99, 95% CI 0.987, 0.996) and night-time occurrence of OHCA (OR 0.67, 95% CI 0.53, 0.83). Six further variables in the final model (sex, call response interval, incident location (home or other), who witnessed collapse (bystander or not witnessed), urban or rural location, and the COVID period) were involved in significant interactions. Bystander defibrillation was in general less likely in urban settings and at home locations. Whilst women were less likely to receive bystander defibrillation overall, in witnessed OHCAs, occurring outside the home, in urban areas and outside of the COVID-19 period women were more likely, to receive bystander defibrillation., Conclusions: Defibrillation by bystanders has increased incrementally over time in Ireland. Interventions to address sex and age-based disparities, alongside interventions to increase bystander defibrillation at night, in urban settings and at home locations are required., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘TB has research, clinical and educational roles in resuscitation care. He is a member of the Pre-Hospital Emergency Care Council (Ireland). All authors declare no conflict of interest’., (© 2024 The Author(s).)

Aims: To explore predictors of bystander CPR (i.e. any CPR performed prior to EMS arrival) in Ireland over the period 2012-2020. To examine the relationship between bystander CPR and key health system developments during this period., Methods: National level out-of-hospital cardiac arrest (OHCA) registry data relating to unwitnessed, and bystander witnessed OHCA were interrogated. Logistic regression models were built, then refined by fitting predictors, performing stepwise variable selection and by adding pairwise interactions that improved fit. Missing data sensitivity analyses were conducted using multiple imputation., Results: The data included 18,177 OHCA resuscitation attempts of whom 77% had bystander CPR. The final model included ten variables. Four variables (aetiology, incident location, time of day, and who witnessed collapse) were involved in interactions. The COVID-19 period was associated with reduced adjusted odds of bystander CPR (OR 0.77, 95% CI 0.65, 0.92), as were increasing age in years (OR 0.992, 95% CI 0.989, 0.994) and urban location (OR 0.52, 95% CI 0.47, 0.57). Increasing year over time (OR 1.23, 95% CI 1.16, 1.29), and an increased call response interval in minutes (OR 1.017, 95% CI 1.012, 1.022) were associated with increased adjusted odds of bystander CPR., Conclusions: Bystander CPR increased over the study period, and it is likely that health system developments contributed to the yearly increases observed. However, COVID-19 appeared to disrupt this positive trend. Urban OHCA location was associated with markedly decreased odds of bystander CPR compared to rural location. Given its importance bystander CPR in urban areas should be an immediate target for intervention., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘TB has research, clinical and educational roles in resuscitation care. He is a member of the Pre-Hospital Emergency Care Council (Ireland). All authors declare no conflict of interest.’., (© 2024 The Authors.)

Aim: To explore potential predictors of national out-of-hospital cardiac arrest (OHCA) survival, including health system developments and the COVID pandemic in Ireland., Methods: National level OHCA registry data from 2012 through to 2020, relating to unwitnessed, and bystander witnessed OHCA were interrogated. Logistic regression models were built by including predictors through stepwise variable selection and enhancing the models by adding pairwise interactions that improved fit. Missing data sensitivity analyses were conducted using multiple imputation., Results: The data included 18,177 cases. The final model included seventeen variables. Of these nine variables were involved in pairwise interactions. The COVID-19 period was associated with reduced survival (OR 0.61, 95%CI 0.43, 0.87), as were increasing age in years (OR 0.96, 95% CI 0.96, 0.97) and call response interval in minutes (OR 0.97, 95% CI 0.96, 0.99). Amiodarone administration (OR 3.91, 95% CI 2.80, 5.48), urban location (OR 1.40, 95% CI 1.12, 1.77), and chronological year over time (OR 1.14, 95% CI 1.08, 1.20) were associated with increased survival., Conclusions: National survival from OHCA has significantly increased incrementally over time in Ireland. The COVID-19 pandemic was associated with decreased survival even after accounting for potential disruption to key elements of bystander and EMS care. Further research is needed to understand and address the discrepancy between urban and rural OHCA survival. Information concerning pre-event patient health status and inpatient care process may yield important additional insights in future., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘TB has research, clinical and educational roles in resuscitation care. He is a member of the Pre-Hospital Emergency Care Council (Ireland). All authors declare no conflict of interest.’., (© 2024 The Author(s).)

Background: Out-of-hospital cardiac arrest (OHCA) is a leading cause of preventable mortality that now affects almost 3,000 people each year in Ireland. Survival is low at 6-7%, compared to a European average of 8%. The Irish Out-of-Hospital Cardiac Registry (OHCAR) prospectively gathers data on all OHCA in Ireland where emergency medical services attempted resuscitation.The Irish health system has undergone several developments that are relevant to OHCA care in the period 2012-2020. OHCAR data provides a means of exploring temporal trends in OHCA incidence, care, and outcomes over time. It also provides a means of exploring whether system developments were associated with a change in key outcomes.This research aims to summarise key trends in available OHCAR data from the period 2012 - 2020, to explore and model predictors of bystander CPR, bystander defibrillation, and survival, and to explore the hypothesis that significant system level temporal developments were associated with improvements in these outcomes., Methods: The following protocol sets out the relevant background and research approach for an observational study that will address the above aims. Key trends in available OHCAR data (2012 - 2020) will be described and evaluated using descriptive summaries and graphical displays. Multivariable logistic regression will be used to model predictors of 'bystander CPR', 'bystander defibrillation' and 'survival to hospital discharge' and to explore the effects (if any) of system level developments in 2015/2016 and the COVID-19 pandemic (2020) on these outcomes., Discussion: The findings of this research will be used to understand temporal trends in the care processes and outcomes for OHCA in Ireland over the period 2012-2020. The results can further be used to optimise future health system developments for OHCA in both Ireland and internationally., Competing Interests: Competing interests: TB has research, clinical and educational roles in resuscitation care. He is a member of the Pre-Hospital Emergency Care Council (Ireland)., (Copyright: © 2023 Barry T et al.)

Background: The International Liaison Committee on Resuscitation (ILCOR) Research and Registries Working Group previously reported data on systems of care and outcomes of out-of-hospital cardiac arrest (OHCA) in 2015 from 16 national and regional registries. To describe the temporal trends with updated data on OHCA, we report the characteristics of OHCA from 2015 through 2017., Methods: We invited national and regional population-based OHCA registries for voluntary participation and included emergency medical services (EMS)-treated OHCA. We collected descriptive summary data of core elements of the latest Utstein style recommendation during 2016 and 2017 at each registry. For registries that participated in the previous 2015 report, we also extracted the 2015 data., Results: Eleven national registries in North America, Europe, Asia, and Oceania, and 4 regional registries in Europe were included in this report. Across registries, the estimated annual incidence of EMS-treated OHCA was 30.0-97.1 individuals per 100,000 population in 2015, 36.4-97.3 in 2016, and 40.8-100.2 in 2017. The provision of bystander cardiopulmonary resuscitation (CPR) varied from 37.2% to 79.0% in 2015, from 2.9% to 78.4% in 2016, and from 4.1% to 80.3% in 2017. Survival to hospital discharge or 30-day survival for EMS-treated OHCA ranged from 5.2% to 15.7% in 2015, from 6.2% to 15.8% in 2016, and from 4.6% to 16.4% in 2017., Conclusion: We observed an upward temporal trend in provision of bystander CPR in most registries. Although some registries showed favourable temporal trends in survival, less than half of registries in our study demonstrated such a trend., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: To use quality indicators to study the management of ST-segment elevation myocardial infarction (STEMI) in different regions., Methods and Results: Prospective cohort study of STEMI within 24 h of symptom onset (11 462 patients, 196 centres, 26 European Society of Cardiology members, and 3 affiliated countries). The median delay between arrival at a percutaneous cardiovascular intervention (PCI) centre and primary PCI was 40 min (interquartile range 20-74) with 65.8% receiving PCI within guideline recommendation of 60 min. A third of patients (33.2%) required transfer from their initial hospital to one that could perform emergency PCI for whom only 27.2% were treated within the quality indicator recommendation of 120 min. Radial access was used in 56.6% of all primary PCI, but with large geographic variation, from 76.4 to 9.1%. Statins were prescribed at discharge to 98.7% of patients, with little geographic variation. Of patients with a history of heart failure or a documented left ventricular ejection fraction ≤40%, 84.0% were discharged on an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and 88.7% were discharged on beta-blockers., Conclusion: Care for STEMI shows wide geographic variation in the receipt of timely primary PCI, and is in contrast with the more uniform delivery of guideline-recommended pharmacotherapies at time of hospital discharge., Competing Interests: Conflict of interest: P.L., C.L., M.S., S.M.S., J.L., K.F.A., A.G., E.M., G.B., H.A.F., P.Š., M.S., J.M., D.B, D.A., Z.K., S.S., A.M.M., M.Q., and P.P.K. have nothing to disclose. U.Z. reports: Consulting fees from Amgen, personal fees from Amgen; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Astra Zeneca, Chiesi, Pfizer; participation on a Data Safety Monitoring Board or Advisory Board Astra Zeneca, Chiesi, Bayer, Boehriger Ingelhein, outside the submitted work. R.C. reports participation on a Data Safety Monitoring Board or Advisory Board with personal payments from Daiichi Sankyo, Novartis, Boehringer Ingelheim, Lilly, outside the submitted work. Z.I. reports consulting fees with direct payments to author from Pfizer, Astra Zeneca, Bayer; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, Sanofi, Boehringer Ingelheim outside the submitted work. Z.M. reports consulting fees from Amgen; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Astra Zeneca, Chiesi, Pfizer; participation on a Data Safety Monitoring Board or Advisory Board from Astra Zeneca, Chiesi, Bayer, Boehriger Ingelhein outside the submitted work. T.M. reports receipt of funding from Estonian Research Council [PRG435]; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from AstraZeneca, Eesti outside the submitted work. C.P.G. reports grants or contracts from British Heart Foundation, National Institute for Health Research, Horizon 2020, Abbott Diabetes, Bristol Myers Squibb/Pfizer; consulting fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Chiesi, Daiichi Sankyo, Menarini; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events fromBoehringer Ingelheim, Chiesi, Daiichi Sankyo, Menarini; support for attending meetings and/or travel from AstraZeneca, Bayer; patents planned, issued, or pending—FIND-AF; participation on a Data Safety Monitoring Board or Advisory Board—TARGET CTCA DSMB, DANBLOCK DSMB; leadership or fiduciary role in other board, society, committee, or advocacy group, for ESC EuroHeart, NICE IAC, ESC Quality Indicator Committee Chair, outside the submitted work. A.P.M. reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events—AstraZeneca, Novartis; participation in study committees—Bayer, Fresenius, outside the present work., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Wetting of carbon surfaces is one of the most widespread, yet poorly understood, physical phenomena. Control over wetting properties underpins the operation of aqueous energy-storage devices and carbon-based filtration systems. Electrowetting, the variation in the contact angle with an applied potential, is the most straightforward way of introducing control over wetting. Here, we study electrowetting directly on graphitic surfaces with the use of aqueous electrolytes to show that reversible control of wetting can be achieved and quantitatively understood using models of the interfacial capacitance. We manifest that the use of highly concentrated aqueous electrolytes induces a fully symmetric and reversible wetting behavior without degradation of the substrate within the unprecedented potential window of 2.8 V. We demonstrate where the classical "Young-Lippmann" models apply, and break down, and discuss reasons for the latter, establishing relations among the applied bias, the electrolyte concentration, and the resultant contact angle. The approach is extended to electrowetting at the liquid|liquid interface, where a concentrated aqueous electrolyte drives reversibly the electrowetting response of an insulating organic phase with a significantly decreased potential threshold. In summary, this study highlights the beneficial effect of highly concentrated aqueous electrolytes on the electrowettability of carbon surfaces, being directly related to the performance of carbon-based aqueous energy-storage systems and electronic and microfluidic devices., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Introduction: Gestational trophoblastic disease (GTD) encompasses a range of trophoblastic disorders from hydatidiform mole (HM), to malignant gestational trophoblastic neoplasia (GTN). The exact molecular mechanisms of GTN remain unknown. Dysregulation and dysfunction of programmed cell death 4 (PDCD4)have been observed in many cancers. The roles of PDCD4 in GTD have not been previously reported., Methods: A total of 161 cases of formalin-fixed, paraffin-embedded trophoblast blocks, and 36 cases of fresh trophoblast tissues were collected, including normal first trimester placentas, HM, and invasive HM. Choriocarcinoma cells JAR and JEG-3 were employed. The expressions of PDCD4 and small ubiquitin-like modifier 2/3 (SUMO2/3) were examined by immunohistochemistry, quantitative reverse transcription PCR and Western blotting in trophoblastic tissues and cells. The relationship between SUMOylation and PDCD4 was investigated. The effects of PDCD4 on proliferation, invasion, and migration of choriocarcinoma cells were evaluated by Cell Counting Kit-8 and transwell assays post siRNA transfection. Extracellular Matrix & Adhesion Profiler PCR Array was used to screen the downstream molecules of PDCD4., Results: PDCD4 was significantly repressed in HM tissues. Loss of PDCD4 expression was demonstrated in 90% invasive HMs. Choriocarcinoma cells also displayed with suppressed PDCD4 expression. The varied expression of PDCD4 was paralleled by SUMO2/3. Inhibition of SUMOylation reduced the expression of PDCD4. Silencing of PDCD4promoted proliferation/migration/invasion, upregulatedMMP3/MMP8/ITGB2, and downregulated TIMP1/TIMP2 in choriocarcinoma cells., Discussion: Our results suggest that reduced SUMOylation is one reason for suppressed PDCD4 in GTD. Loss of PDCD4 likely determines the malignant phenotype of GTN by dysregulating some members of the MMPs/TIMPs/integrins complex., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aims: The aim of this study was to determine the contemporary use of reperfusion therapy in the European Society of Cardiology (ESC) member and affiliated countries and adherence to ESC clinical practice guidelines in patients with ST-elevation myocardial infarction (STEMI)., Methods and Results: Prospective cohort (EURObservational Research Programme STEMI Registry) of hospitalized STEMI patients with symptom onset <24 h in 196 centres across 29 countries. A total of 11 462 patients were enrolled, for whom primary percutaneous coronary intervention (PCI) (total cohort frequency: 72.2%, country frequency range 0-100%), fibrinolysis (18.8%; 0-100%), and no reperfusion therapy (9.0%; 0-75%) were performed. Corresponding in-hospital mortality rates from any cause were 3.1%, 4.4%, and 14.1% and overall mortality was 4.4% (country range 2.5-5.9%). Achievement of quality indicators for reperfusion was reported for 92.7% (region range 84.8-97.5%) for the performance of reperfusion therapy of all patients with STEMI <12 h and 54.4% (region range 37.1-70.1%) for timely reperfusion., Conclusions: The use of reperfusion therapy for STEMI in the ESC member and affiliated countries was high. Primary PCI was the most frequently used treatment and associated total in-hospital mortality was below 5%. However, there was geographic variation in the use of primary PCI, which was associated with differences in in-hospital mortality., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Introduction: In this study we examined the hypothesis that a hypoxic intrauterine environment causes mitochondrial dysfunction of trophoblasts in fetal growth restriction (FGR)., Methods: The mtDNA content, mRNA levels of mitochondrial encoded genes (ND6, COX I), mitochondrial membrane proteins (COX I, COX IV and VDAC), HIF-1α and BINP3 (mitophagy receptor) protein levels were examined in FGR placentas and normal placentas. The mitochondrial function (ATP production and mitochondrial membrane potential-ΔΨm) and above related proteins were further examined in hypoxic HTR-8/SVneo cells induced by cobalt chloride (CoCl2). Mitophagy and its regulating mechanism under hypoxia in FGR was also investigated., Results: Compared with normal controls, both FGR placentas and CoCl2-treated trophoblast cells demonstrated statistically lower mtDNA content, reduced mRNAs of mitochondrial encoding genes, and decreased mitochondrial membrane proteins, accompanied by increased HIF-1α. Mitochondrial functions were impaired as demonstrated by decreased ATP production, and, reduced ΔΨm in CoCl2-treated cells. Meanwhile, mitophagy was markedly enhanced as indicated by increased LC3 fluorescent puncta in mitochondria of hypoxic trophoblastic cells. The upregulated BINP3 expression was demonstrated in FGR placentas as well as in hypoxic trophoblastic cells., Discussion: We demonstrated that hypoxic conditions lead to impaired mitochondrial function in trophoblasts in FGR. Reduced mtDNA may be associated with enhanced mitophagy via activating HIF-1α/BINP3 signalling pathway, that may, in turn, affect nutrition and energy transfer to the growth-restricted fetus., Competing Interests: Declaration of competing interest There are no conflicts of interest nor financial interests associated with this work., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: In Ireland, the MERIT 3 scheme enables doctors to volunteer as cardiac arrest community first responders and receive text message alerts from emergency medical services (EMS) to facilitate early care., Aim: To establish the sustainability, systems and clinical outcomes of a novel, general practice based, cardiac arrest first response initiative over a four-year period., Methods: Data on alerts, responses, incidents and outcomes were gathered prospectively using EMS control data, incident data reported by responders and corroborative data from the national Out-of-Hospital Cardiac Arrest Registry., Results: Over the period 2016-2019, 196 doctors joined MERIT 3 and 163 (83.2%) were alerted on one or more occasions; 61.3% of those alerted responded to at least one alert. Volunteer doctors attended 300 patients of which 184 (61.3%) had suffered OHCA and had a resuscitation attempt. Responders arrived to OHCA before EMS on 75 occasions (40.8%), initiated chest compressions on seven occasions (3.8%), and brought the first defibrillator on 42 occasions (22.8%). Information on the first monitored rhythm was available for 149/184 (81.0%) patients and was shockable in 30/149 (20.1%); in 9/30 cases, shocks were administered by responders. The overall survival rate was 11.0% (national survival rate 7.3%). Doctors also provided advanced life support and were closely involved in decision making on ceasing resuscitation., Conclusion: The MERIT 3 initiative in Ireland has been sustained over a four-year period and has demonstrated the ability of volunteer doctors to provide early care for OHCA patients as well as more complex interventions including end-of-life care. Further development of this strategy is warranted., (© 2021 The Author(s).)

Introduction: The aim of this research was to study the alteration of three key tight junction proteins, to explore whether they were involved in the occurrence of prelabor rupture of the membrane (PROM) and to determine the correlation with intrauterine infection., Methods: A total of 208 women were enrolled between January 2015 to December 2018, including those with preterm and term PROM (PROM group) and normal pregnancies with intact fetal membrane (control group). We investigated the expressions of three key TJ molecules (Zonula occludens-1, Occludin and Claudin-5) in fetal membranes. The localization and expression of Zonula occludens-1 (ZO-1) in the amnion and chorion were studied by immunohistochemistry assay. The associations between ZO-1 expression levels and extent of inflammatory reactions as well as other obstetric characteristics were further studied using Spearman's rank correlation test and Mann-Whitney U test., Results: ZO-1 was significantly downregulated in PROM group compared with control group (P < 0.001), whereas no significant changes were found for Occludin and Claudin-5. ZO-1 expression was reduced in the chorion and amnion layers in PROM group compared with that in control group, which showed a significant difference (P < 0.01), but no significant differences were observed between the preterm PROM and term PROM groups (P > 0.05). The expression levels of ZO-1 in the chorion were negatively correlated with the stage/grade of acute chorioamnionitis (P < 0.05)., Discussion: Our study suggests that inflammation-related downregulation of ZO-1 might be a pivotal event in the occurrence of PROM, which helps to clarify the mechanism of membrane rupture caused by infection., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: More than 3.5 million invasive coronary angiographies (ICA) are performed in Europe annually. Approximately 2 million of these invasive procedures might be reduced by noninvasive tests because no coronary intervention is performed. Computed tomography (CT) is the most accurate noninvasive test for detection and exclusion of coronary artery disease (CAD). To investigate the comparative effectiveness of CT and ICA, we designed the European pragmatic multicentre DISCHARGE trial funded by the 7th Framework Programme of the European Union (EC-GA 603266)., Methods: In this trial, patients with a low-to-intermediate pretest probability (10-60 %) of suspected CAD and a clinical indication for ICA because of stable chest pain will be randomised in a 1-to-1 ratio to CT or ICA. CT and ICA findings guide subsequent management decisions by the local heart teams according to current evidence and European guidelines., Results: Major adverse cardiovascular events (MACE) defined as cardiovascular death, myocardial infarction and stroke as a composite endpoint will be the primary outcome measure. Secondary and other outcomes include cost-effectiveness, radiation exposure, health-related quality of life (HRQoL), socioeconomic status, lifestyle, adverse events related to CT/ICA, and gender differences., Conclusions: The DISCHARGE trial will assess the comparative effectiveness of CT and ICA., Key Points: • Coronary artery disease (CAD) is a major cause of morbidity and mortality. • Invasive coronary angiography (ICA) is the reference standard for detection of CAD. • Noninvasive computed tomography angiography excludes CAD with high sensitivity. • CT may effectively reduce the approximately 2 million negative ICAs in Europe. • DISCHARGE addresses this hypothesis in patients with low-to-intermediate pretest probability for CAD.

Objective: Recent studies have established that cardiac MDCT generates high-quality images of the cardiac valves. Images are acquired during a single breath-hold (inspiration) after the injection of iodinated contrast material (5 mL/s) followed by a saline bolus chaser. Incremental data sets are then reconstructed throughout the R-R interval, and after transfer to a workstation, specialized software combines data sets sequentially to generate cine loops of the heart throughout the cardiac cycle. The purpose of this article is to describe the cardiac MDCT techniques allowing optimal cardiac valve depiction and to illustrate the MDCT appearances of the most important valve diseases., Conclusion: Cardiac MDCT provides an excellent imaging method for illustrating cardiac valve disease. Radiologists should be aware of the various appearances of the common and most important cardiac valve diseases on cardiac MDCT.

AlphaIIbbeta3, the major membrane protein on the surface of platelets, is a member of the integrin family of heterodimeric adhesion receptors. The alphaIIb and beta3 subunits are each composed of a short cytoplasmic tail, a single transmembrane domain, and a large, extracellular region that consists of a series of linked domains. Recent structural analyses have provided insights into the organization of this and other integrins and how a signal is initiated at its cytoplasmic tail to transform the extracellular domain of alphaIIbbeta3 into a functional receptor for fibrinogen or von Willebrand factor to support platelet aggregation and thrombus formation. These functions of alphaIIbbeta3 have been targeted for antithrombotic therapy, and intravenous alphaIIbbeta3 antagonists have been remarkably effective in the setting of percutaneous coronary interventions, showing both short-term and long-term mortality benefits. However, the development of oral antagonists has been abandoned on the basis of excess of mortality in clinical trials, and the extension of therapy with existing alphaIIbbeta3 antagonists to broadly treat acute coronary syndromes has not fully met expectations. An in-depth understanding of how antagonists engage and influence the function of alphaIIbbeta3 and platelets in the context of the new structural insights may explain its salutary and potential deleterious effects.