Targeting IGF2-IGF1R Signaling to Reprogram the Tumor Microenvironment for Enhanced Viro-Immunotherapy.

BACKGROUND: The FDA approval of oncolytic herpes simplex-1 virus (oHSV) therapy underscores its therapeutic promise and safety as a cancer immunotherapy. Despite this promise, the current efficacy of oHSV is significantly limited to a small subset of patients largely due to the resistance in tumor and tumor microenvironment (TME). METHODS: RNA sequencing (RNA-Seq) was used to identify molecular targets of oHSV resistance. Intracranial human and murine glioma or breast cancer brain metastasis (BCBM) tumor-bearing mouse models were employed to elucidate the mechanism underlying oHSV therapy-induced resistance. RESULTS: Transcriptome analysis identified IGF2 as one of the top secreted proteins following oHSV treatment. Moreover, IGF2 expression was significantly upregulated in 10 out of 14 recurrent GBM patients after treatment with oHSV, rQNestin34.5v.2 (71.4%) (p=0.0020) (ClinicalTrials.gov, NCT03152318). Depletion of IGF2 substantially enhanced oHSV-mediated tumor cell killing in vitro and improved survival of mice bearing BCBM tumors in vivo. To mitigate the oHSV-induced IGF2 in the TME, we constructed a novel oHSV, oHSV-D11mt, secreting a modified IGF2R domain 11 (IGF2RD11mt) that acts as IGF2 decoy receptor. Selective blocking of IGF2 by IGF2RD11mt significantly increased cytotoxicity, reduced oHSV-induced neutrophils/PMN-MDSCs infiltration, and reduced secretion of immune suppressive/proangiogenic cytokines, while increased CD8+cytotoxic T lymphocytes (CTLs) infiltration, leading to enhanced survival in GBM or BCBM tumor-bearing mice. CONCLUSION: This is the first study reporting that oHSV-induced secreted IGF2 exerts a critical role in resistance to oHSV therapy, which can be overcome by oHSV-D11mt as a promising therapeutic advance for enhanced viro-immunotherapy.

esRAGE-expressing oHSV enhances anti-tumor efficacy by inhibition of endothelial cell activation.

High-mobility group box 1 (HMGB1) is a damage-associated molecular pattern (DAMP) molecule that plays an important role in inflammation and tumorigenesis. Receptor for advanced glycation end products (RAGE) is one of the major receptors to which extracellular HMGB1 binds to mediate its activity. RAGE is highly expressed on the endothelial cells (ECs) and regulates endothelial permeability during inflammation. Here, we introduced the endogenous secretory form of RAGE (esRAGE) as a decoy receptor for RAGE ligands into an oncolytic herpes simplex virus 1 (oHSV) (OVesRAGE), which, upon release, can function to block RAGE signaling. OVesRAGE significantly decreased phosphorylation of MEK1/2 and Erk and increased cleaved PARP in glioblastoma (GBM) cells in vitro and in vivo. oHSV-infected GBM cells co-cultured with ECs were used to test OVesRAGE effect on EC activation, vessel leakiness, virus replication, and tumor cell killing. OVesRAGE could effectively secrete esRAGE and rescue virus-induced EC migration and activation. Reduced EC activation facilitated virus replication in tumor cells when co-cultured with ECs. Finally, OVesRAGE significantly enhanced therapeutic efficacy in GBM-bearing mice. Collectively, our data demonstrate that HMGB1-RAGE signaling could be a promising target and that its inhibition is a feasible approach to improve the efficacy of oHSV therapy.

Caenorhabditis elegans to Model the Capacity of Ascorbic Acid to Reduce Acute Nitrite Toxicity under Different Feed Conditions: Multivariate Analytics on Behavioral Imaging.

Nitrocompounds are present in the environment and human diet and form part of vegetables and processed meat products as additives. These compounds are related to negative impacts on human and animal health. The protective effect of ascorbic acid has been demonstrated by some biological systems as regards several nitrocompounds. This work focused on studying the possibility of modeling this effect on nitrite toxicity with the model Caenorhabditis elegans. The three factors studied in this work were ascorbic acid concentration, nitrite exposure concentration, and presence/absence of food. The protective effect was evaluated by scoring lethality and its impact on behavior by means of multivariate statistical methods and imaging analytics. The effects of nitrite and the influence of food availability were evidenced. Apart from increasing lethality, nitrite had disruption effects on movements. All the observed symptoms reduced when ascorbic acid was administered, and it diminished lethality in all cases. Ascorbic acid maintained nematodes' postural capacities. The results suggest that nitrites' nonspecific toxicity in C. elegans can be mitigated by ascorbic acid, as previously evidenced in other biological systems. Thus, our results reveal the ability of C. elegans to reproduce the known protective effect of ascorbic acid against nitrite.

Probabilistic Evaluation of 3D Surfaces Using Statistical Shape Models (SSM).

Inspecting a 3D object which shape has elastic manufacturing tolerances in order to find defects is a challenging and time-consuming task. This task usually involves humans, either in the specification stage followed by some automatic measurements, or in other points along the process. Even when a detailed inspection is performed, the measurements are limited to a few dimensions instead of a complete examination of the object. In this work, a probabilistic method to evaluate 3D surfaces is presented. This algorithm relies on a training stage to learn the shape of the object building a statistical shape model. Making use of this model, any inspected object can be evaluated obtaining a probability that the whole object or any of its dimensions are compatible with the model, thus allowing to easily find defective objects. Results in simulated and real environments are presented and compared to two different alternatives.

Toxicological implications of amplifying the antibacterial activity of gallic acid by immobilisation on silica particles: A study on C. elegans.

Immobilisation of natural compounds on solid supports to amplify antimicrobial properties has reported successful results, but modifications to physico-chemical properties can also imply modifications from a toxicological viewpoint. This work aimed to study the immobilising process of gallic acid in the antibacterial activity of L. innocua and its toxicological properties in vivo using Caenorhabditis elegans. The experiment was based on obtaining the minimum bactericidal concentration for free and immobilised gallic acid by comparing lethality, locomotion behaviour, chemotaxis and thermal stress resistance on C.elegans at those concentrations. The results showed a lowering minimum bactericidal concentration and modifications to nematode responses. Increased lethality and velocity of movements was observed. Immobilisation increased the repellent effect of gallic acid with a negative chemotaxis index. Thermal stress resistance was also affected, with higher mortality for immobilised gallic acid compared to bare particles and free gallic acid. Thus despite evidencing a generalised increase in the toxicity of gallic acid in vivo, lowering the minimum bactericidal concentration allowed a bacterial reduction of 99 % with less than one third of mortality for the nematodes exposed to free gallic acid.

Carotid plaque is a predictor of major adverse cardiac and cerebrovascular events in patients undergoing coronary angiography.

Background: Carotid disease, measured as carotid intima-media thickness (CIMT) and carotid plaque (CP), is associated with major adverse cardiac and cerebrovascular events (MACCE) in people without the previous atherosclerotic disease; however, there are few published data in patients undergoing coronary angiography. The aim of the study is to determinate if the carotid disease is associated with MACCE after coronary angiography. Methods: A total of 390 consecutive patients underwent coronary angiography after exercise echocardiography and carotid ultrasonography between 2002 and 2013. MACCE was defined as stroke, myocardial infarction due to atherosclerosis progression or death due to a stroke or cardiac event. Results: Two patients were lost (0.5%). During a mean follow-up of 6.0 years (standard deviation of 2.9), 52 patients (13.4%) suffered MACCE. 1, 5, and 10 years, event-free survival was 96.4% (1.0), 88.7% (1.7), and 81.4% (2.8), respectively. Event rates at 10 years were higher in the CP group (23.2% vs. 10.2%, p = 0.013) and in the CIMT > 0.9 mm group (25.9% vs. 13.3%, p = 0.023). Multivariate analysis showed smoking habit (hazard ratio [HR] 2.51, 95% confidence interval [CI] 1.36-4.62, p = 0.003), glomerular filtration rate (HR 0.98, 95% CI 0.98-0.99), aortic stenosis (HR 2.99, 95% CI 1.24-7.21, p = 0.014), incomplete/no coronary revascularization (HR 1.97, 95% CI 1.06-3.67, p = 0.033), insulin treatment (HR 2.63, 95% CI 1.30-5.31, p = 0.006), and CP (HR 2.36, 95% CI 1.02-5.44, p = 0.044) as predictors of MACCE. Conclusions: CP is an independent predictor of MACCE in patients undergoing coronary angiography.

Introducción: La enfermedad carotídea, definida como grosor de íntima media (GIMC) y placa (PC), se asocia con eventos adversos cardiacos y cerebrovasculares (EACC) en sujetos sin aterosclerosis previa; sin embargo hay pocos datos en pacientes sometidos a coronariografía. El objetivo del estudio es determinar si la enfermedad carotídea se asocia a EACC en pacientes remitidos a coronariografía. Métodos: Entre 2002 y 2013 390 pacientes fueron sometidos a coronariografía tras ecocardiograma de esfuerzo y ecografía carotídea. Se definió EACC como accidente cerebrovascular, infarto de miocardio por progresión aterosclerótica o muerte por accidente cerebrovascular o causa cardiaca. Resultados: Durante un seguimiento medio de 6 años (desviación estándar 2, 9) se registraron 2 pérdidas y 52 eventos (13,4%). La supervivencia media libre de eventos a uno, cinco y diez años fue 96.4% (1.0), 88.7% (1.7) y 81.4% (2.8). Hubo mayor número de eventos a 10 años en el grupo de PC (23.2% frente 10.2%, p = 0.013) y GIMC > 0.9 mm (25,9% frente 13.3%, p = 0.023). En el análisis multivariado los predictores de EACC fueron tabaquismo (hazard ratio [HR] 2.51, intervalo de confianza [IC] al 95% 1.36-4.62, p = 0.003), filtrado glomerular renal (HR 0.98 IC95% 0.98-0.99), estenosis aórtica (HR 2.99, IC 95% 1.24-7.21, p = 0.014), revascularización incompleta/no revascularización (HR 1.97, IC 95% 1.06-3.67, p = 0.033), tratamiento con insulina (HR 2.63, IC 95% 1.30-5.31, p = 0.006) y PC (HR 2.36, 95%CI 1.02-5.44, p = 0.044). Conclusiones: La PC es un predictor independiente de EACC en pacientes sometidos a coronariografía.

Carotid plaque is a predictor of major adverse cardiac and cerebrovascular events in patients undergoing coronary angiography.

INTRODUCTION: Carotid disease, measured as carotid intima-media thickness (CIMT) and carotid plaque (CP), is associated with major adverse cardiac and cerebrovascular events (MACCE) in people without the previous atherosclerotic disease; however, there are few published data in patients undergoing coronary angiography. The aim of the study is to determinate if the carotid disease is associated with MACCE after coronary angiography. METHODS: A total of 390 consecutive patients underwent coronary angiography after exercise echocardiography and carotid ultrasonography between 2002 and 2013. MACCE was defined as stroke, myocardial infarction due to atherosclerosis progression or death due to a stroke or cardiac event. RESULTS: Two patients were lost (0.5%). During a mean follow-up of 6.0 years (standard deviation of 2.9), 52 patients (13.4%) suffered MACCE. 1, 5, and 10 years, event-free survival was 96.4% (1.0), 88.7% (1.7), and 81.4% (2.8), respectively. Event rates at 10 years were higher in the CP group (23.2% vs. 10.2%, p = 0.013) and in the CIMT > 0.9 mm group (25.9% vs. 13.3%, p = 0.023). Multivariate analysis showed smoking habit (hazard ratio [HR] 2.51, 95% confidence interval [CI] 1.36-4.62, p = 0.003), glomerular filtration rate (HR 0.98, 95% CI 0.98-0.99), aortic stenosis (HR 2.99, 95% CI 1.24-7.21, p = 0.014), incomplete/no coronary revascularization (HR 1.97, 95% CI 1.06-3.67, p = 0.033), insulin treatment (HR 2.63, 95% CI 1.30-5.31, p = 0.006), and CP (HR 2.36, 95% CI 1.02-5.44, p = 0.044) as predictors of MACCE. CONCLUSIONS: CP is an independent predictor of MACCE in patients undergoing coronary angiography.

INTRODUCCIÓN: La enfermedad carotídea, definida como grosor de íntima media (GIMC) y placa (PC), se asocia con eventos adversos cardiacos y cerebrovasculares (EACC) en sujetos sin aterosclerosis previa; sin embargo hay pocos datos en pacientes sometidos a coronariografía. El objetivo del estudio es determinar si la enfermedad carotídea se asocia a EACC en pacientes remitidos a coronariografía. MÉTODOS: Entre 2002 y 2013 390 pacientes fueron sometidos a coronariografía tras ecocardiograma de esfuerzo y ecografía carotídea. Se definió EACC como accidente cerebrovascular, infarto de miocardio por progresión aterosclerótica o muerte por accidente cerebrovascular o causa cardiaca. RESULTADOS: Durante un seguimiento medio de 6 años (desviación estándar 2, 9) se registraron 2 pérdidas y 52 eventos (13,4%). La supervivencia media libre de eventos a uno, cinco y diez años fue 96.4% (1.0), 88.7% (1.7) y 81.4% (2.8). Hubo mayor número de eventos a 10 años en el grupo de PC (23.2% frente 10.2%, p = 0.013) y GIMC > 0.9 mm (25,9% frente 13.3%, p = 0.023). En el análisis multivariado los predictores de EACC fueron tabaquismo (hazard ratio [HR] 2.51, intervalo de confianza [IC] al 95% 1.36-4.62, p = 0.003), filtrado glomerular renal (HR 0.98 IC95% 0.98-0.99), estenosis aórtica (HR 2.99, IC 95% 1.24-7.21, p = 0.014), revascularización incompleta/no revascularización (HR 1.97, IC 95% 1.06-3.67, p = 0.033), tratamiento con insulina (HR 2.63, IC 95% 1.30-5.31, p = 0.006) y PC (HR 2.36, 95%CI 1.02-5.44, p = 0.044). CONCLUSIONES: La PC es un predictor independiente de EACC en pacientes sometidos a coronariografía.

Carotid plaque is a predictor of major adverse cardiac and cerebrovascular events in patients undergoing coronary angiography / La presencia de placa carotídea es predictor de eventos adversos cardiacos y cerebrovasculares en sujetos sometidos a coronariografía

Abstract Introduction: Carotid disease, measured as carotid intima-media thickness (CIMT) and carotid plaque (CP), is associated with major adverse cardiac and cerebrovascular events (MACCE) in people without the previous atherosclerotic disease; however, there are few published data in patients undergoing coronary angiography. The aim of the study is to determinate if the carotid disease is associated with MACCE after coronary angiography. Methods: A total of 390 consecutive patients underwent coronary angiography after exercise echocardiography and carotid ultrasonography between 2002 and 2013. MACCE was defined as stroke, myocardial infarction due to atherosclerosis progression or death due to a stroke or cardiac event. Results: Two patients were lost (0.5%). During a mean follow-up of 6.0 years (standard deviation of 2.9), 52 patients (13.4%) suffered MACCE. 1, 5, and 10 years, event-free survival was 96.4% (1.0), 88.7% (1.7), and 81.4% (2.8), respectively. Event rates at 10 years were higher in the CP group (23.2% vs. 10.2%, p = 0.013) and in the CIMT > 0.9 mm group (25.9% vs. 13.3%, p = 0.023). Multivariate analysis showed smoking habit (hazard ratio [HR] 2.51, 95% confidence interval [CI] 1.36-4.62, p = 0.003), glomerular filtration rate (HR 0.98, 95% CI 0.98-0.99), aortic stenosis (HR 2.99, 95% CI 1.24-7.21, p = 0.014), incomplete/no coronary revascularization (HR 1.97, 95% CI 1.06-3.67, p = 0.033), insulin treatment (HR 2.63, 95% CI 1.30-5.31, p = 0.006), and CP (HR 2.36, 95% CI 1.02-5.44, p = 0.044) as predictors of MACCE. Conclusions: CP is an independent predictor of MACCE in patients undergoing coronary angiography.

Resumen La enfermedad carotídea, definida como grosor de íntima media (GIMC) y placa (PC), se asocia con eventos adversos cardiacos y cerebrovasculares (EACC) en sujetos sin aterosclerosis previa; sin embargo hay pocos datos en pacientes sometidos a coronariografía. El objetivo del estudio es determinar si la enfermedad carotídea se asocia a EACC en pacientes remitidos a coronariografía Métodos: Entre 2002 y 2013 390 pacientes fueron sometidos a coronariografía tras ecocardiograma de esfuerzo y ecografía carotídea. Se definió EACC como accidente cerebrovascular, infarto de miocardio por progresión aterosclerótica o muerte por accidente cerebrovascular o causa cardiaca. Resultados: Durante un seguimiento medio de 6 años (desviación estándar 2, 9) se registraron 2 pérdidas y 52 eventos (13,4%). La supervivencia media libre de eventos a uno, cinco y diez años fue 96.4% (1.0), 88.7% (1.7) y 81.4% (2.8). Hubo mayor número de eventos a 10 años en el grupo de PC (23.2% frente 10.2%, p = 0.013) y GIMC > 0.9 mm (25,9% frente 13.3%, p = 0.023). En el análisis multivariado los predictores de EACC fueron tabaquismo (hazard ratio [HR] 2.51, intervalo de confianza [IC] al 95% 1.36-4.62, p = 0.003), filtrado glomerular renal (HR 0.98 IC95% 0.98-0.99), estenosis aórtica (HR 2.99, IC 95% 1.24-7.21, p = 0.014), revascularización incompleta/no revascularización (HR 1.97, IC 95% 1.06-3.67, p = 0.033), tratamiento con insulina (HR 2.63, IC 95% 1.30-5.31, p = 0.006) y PC (HR 2.36, 95%CI 1.02-5.44, p = 0.044). Conclusiones: La PC es un predictor independiente de EACC en pacientes sometidos a coronariografía.

Subclinical carotid atherosclerosis predicts all-cause mortality and cardiovascular events in obese patients with negative exercise echocardiography.

BACKGROUND: Obesity is a major health problem due to its high prevalence. The relationship between obesity and cardiovascular disease is unclear. Some studies agree that certain conditions associated with obesity, such as physical inactivity or cardiovascular risk factors, are responsible for cardiovascular risk excess among obese people. Carotid intima-media thickness and carotid plaques (CP) have been associated with cardiovascular adverse events in healthy populations, and recent data suggest a higher prevalence of subclinical carotid atherosclerosis in obese and metabolically unhealthy patients. However, there are no studies correlating subclinical atherosclerosis and adverse events (AE) in obese subjects. AIM: To determine the association between carotid disease and AE in obese patients with negative exercise echocardiography (EE). METHODS: From January 1, 2006 to December 31, 2010, 2000 consecutive patients with a suspicion of coronary artery disease were submitted for EE and carotid ultrasonography. Exclusion criteria included previous vascular disease, left ventricular ejection fraction < 50%, positive EE, significant valvular heart disease and inferior to submaximal EE. An AE was defined as all-cause mortality, myocardial infarction and cerebrovascular accident. Subclinical atherosclerosis was defined as CP presence according to Manheim and the American Society of Echocardiography Consensus. RESULTS: Of the 652 patients who fulfilled the inclusion criteria, 226 (34.7%) had body mass indexes ≥ 30 kg/m2, and 76 of them (33.6%) had CP. During a mean follow-up time of 8.2 (2.1) years, 27 AE were found (11.9%). Mean event-free survival at 1, 5 and 10 years was 99.1% (0.6), 95.1% (1.4) and 86.5% (2.7), respectively. In univariate analysis, CP predicted AE [hazard ratio (HR) 2.52, 95% confidence interval (CI) 1.17-5.46; P = 0.019]. In multivariable analysis, the presence of CP remained a predictor of AE (HR 2.26, 95%CI 1.04-4.95, P = 0.041). Other predictors identified were glomerular filtration rate (HR 0.98, 95%CI 0.96-0.99; P = 0.023), peak metabolic equivalents (HR 0.83, 95%CI 0.70-0.99, P = 0.034) and moderate mitral regurgitation (HR 5.02, 95%CI 1.42-17.75, P = 0.012). CONCLUSION: Subclinical atherosclerosis defined by CP predicts AE in obese patients with negative EE. These patients could benefit from aggressive prevention measures.

A System for In-Line 3D Inspection without Hidden Surfaces.

This work presents a 3D scanner able to reconstruct a complete object without occlusions, including its surface appearance. The technique presents a number of differences in relation to current scanners: it does not require mechanical handling like robot arms or spinning plates, it is free of occlusions since the scanned part is not resting on any surface and, unlike stereo-based methods, the object does not need to have visual singularities on its surface. This system, among other applications, allows its integration in production lines that require the inspection of a large volume of parts or products, especially if there is an important variability of the objects to be inspected, since there is no mechanical manipulation. The scanner consists of a variable number of industrial quality cameras conveniently distributed so that they can capture all the surfaces of the object without any blind spot. The object is dropped through the common visual field of all the cameras, so no surface or tool occludes the views that are captured simultaneously when the part is in the center of the visible volume. A carving procedure that uses the silhouettes segmented from each image gives rise to a volumetric representation and, by means of isosurface generation techniques, to a 3D model. These techniques have certain limitations on the reconstruction of object regions with particular geometric configurations. Estimating the inherent maximum error in each area is important to bound the precision of the reconstruction. A number of experiments are presented reporting the differences between ideal and reconstructed objects in the system.

A Portable Dynamic Laser Speckle System for Sensing Long-Term Changes Caused by Treatments in Painting Conservation.

Dynamic laser speckle (DLS) is used as a reliable sensor of activity for all types of materials. Traditional applications are based on high-rate captures (usually greater than 10 frames-per-second, fps). Even for drying processes in conservation treatments, where there is a high level of activity in the first moments after the application and slower activity after some minutes or hours, the process is based on the acquisition of images at a time rate that is the same in moments of high and low activity. In this work, we present an alternative approach to track the drying process of protective layers and other painting conservation processes that take a long time to reduce their levels of activity. We illuminate, using three different wavelength lasers, a temporary protector (cyclododecane) and a varnish, and monitor them using a low fps rate during long-term drying. The results are compared to the traditional method. This work also presents a monitoring method that uses portable equipment. The results present the feasibility of using the portable device and show the improved sensitivity of the dynamic laser speckle when sensing the long-term process for drying cyclododecane and varnish in conservation.

Comparación del valor predictivo pronóstico de los scores TIMI, PAMI, CADILLAC y GRACE en el SCACEST sometido a ICP primario o de rescate / Comparison of the prognostic predictive value of the TIMI, PAMI, CADILLAC, and GRACE risk scores in STEACS undergoing primary or rescue PCI

Introducción y objetivos. Nos planteamos comparar el valor predictivo pronóstico de los scores de riesgo Thrombolysis In Myocardial Infarction (TIMI), Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC), Primary Angioplasty in Myocardial Infarction (PAMI) y Global Registry for Acute Coronary Events (GRACE) para el síndrome coronario agudo con elevación del ST sometido a intervencionismo coronario percutáneo urgente. Métodos. Análisis retrospectivo de una cohorte compuesta por todos los pacientes con un síndrome coronario agudo con elevación del ST tratados en nuestro centro mediante intervencionismo coronario percutáneo urgente entre 2006-2010 (n=1.503). Para cada paciente, calculamos la puntuación de los scores TIMI, PAMI, CADILLAC y GRACE según diferentes variables clínicas. Valoramos el valor predictivo de los cuatro scores para muerte, reinfarto y revascularización de vaso tratado a 30 días y 1 año mediante el estadístico C, empleando para su cálculo regresión logística y curvas ROC. Resultados. Los scores TIMI, PAMI, CADILLAC y GRACE mostraron un excelente valor predictivo para la mortalidad a 30 días y a 1 año (estadístico C; intervalo, 0,8-0,9), con superioridad de los modelos TIMI, CADILLAC y GRACE. El funcionamiento de estos scores fue pobre para la predicción de reinfarto y revascularización de vaso tratado (estadístico C, 0,5-0,6). Conclusiones. Los modelos TIMI, PAMI, CADILLAC y GRACE representan una excelente herramienta para la estratificación del riesgo de mortalidad en los pacientes sometidos a intervencionismo coronario percutáneo primario. Los scores TIMI, CADILLAC y GRACE poseen el mayor poder predictivo. Su utilidad resulta cuestionable para la predicción de reinfarto y revascularización de vaso tratado (AU)

Introduction and objectives. We sought to compare the predictive value of the Thrombolysis In Myocardial Infarction (TIMI), Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC), Primary Angioplasty in Myocardial Infarction (PAMI), and Global Registry for Acute Coronary Events (GRACE) scores for the outcome of ST-segment elevation acute coronary syndrome undergoing urgent percutaneous coronary intervention. Methods. We performed a retrospective analysis of a cohort composed of all consecutive patients with ST-segment elevation acute coronary syndrome treated by urgent percutaneous coronary intervention between 2006 and 2010 (n=1503). TIMI, PAMI, CADILLAC, and GRACE risk scores were calculated for each patient according to different clinical variables. We assessed the predictive accuracy of these scores for death, reinfarction, and target-vessel revascularization at 30 days and 1 year, using the C statistic, which was obtained by means of logistic regression and ROC curves. Results. The TIMI, PAMI, CADILLAC and GRACE showed an excellent predictive value for 30-day and 1-year mortality (C statistic range, 0.8-0.9), with superiority of the TIMI, CADILLAC, and GRACE risk models. The performance of these 4 scores was poor for both reinfarction and target-vessel revascularization (C statistic, 0.5-0.6). Conclusions. The TIMI, PAMI, CADILLAC, and GRACE scores provide excellent information to stratify the risk of mortality in patients treated by percutaneous coronary intervention. The TIMI, CADILLAC, and GRACE models have higher predictive accuracy. The usefulness of these models for reinfarction and target-vessel revascularization prediction is questionable (AU)

Comparison of the prognostic predictive value of the TIMI, PAMI, CADILLAC, and GRACE risk scores in STEACS undergoing primary or rescue PCI.

INTRODUCTION AND OBJECTIVES: We sought to compare the predictive value of the Thrombolysis In Myocardial Infarction (TIMI), Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC), Primary Angioplasty in Myocardial Infarction (PAMI), and Global Registry for Acute Coronary Events (GRACE) scores for the outcome of ST-segment elevation acute coronary syndrome undergoing urgent percutaneous coronary intervention. METHODS: We performed a retrospective analysis of a cohort composed of all consecutive patients with ST-segment elevation acute coronary syndrome treated by urgent percutaneous coronary intervention between 2006 and 2010 (n=1503). TIMI, PAMI, CADILLAC, and GRACE risk scores were calculated for each patient according to different clinical variables. We assessed the predictive accuracy of these scores for death, reinfarction, and target-vessel revascularization at 30 days and 1 year, using the C statistic, which was obtained by means of logistic regression and ROC curves. RESULTS: The TIMI, PAMI, CADILLAC and GRACE showed an excellent predictive value for 30-day and 1-year mortality (C statistic range, 0.8-0.9), with superiority of the TIMI, CADILLAC, and GRACE risk models. The performance of these 4 scores was poor for both reinfarction and target-vessel revascularization (C statistic, 0.5-0.6). CONCLUSIONS: The TIMI, PAMI, CADILLAC, and GRACE scores provide excellent information to stratify the risk of mortality in patients treated by percutaneous coronary intervention. The TIMI, CADILLAC, and GRACE models have higher predictive accuracy. The usefulness of these models for reinfarction and target-vessel revascularization prediction is questionable.