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The persistence of elevated rates of ischemic recurrences despite the use of antiplatelet therapy among patients with atherosclerotic disease together with the understanding of the pivotal role of coagulation in the thrombo-inflammatory processes involved in the pathogenesis of atherosclerosis and its complications has fostered the development of treatments targeting both platelets and coagulation, a strategy known as dual-pathway inhibition (DPI).In this review we discuss the recent advancements in the understanding of the interplay between coagulation, platelets and inflammation involved in the pathophysiology of atherosclerosis and atherothrombosis, as the rationale for the implementation of a DPI strategy. We also discuss the available pharmacodynamic (PD) evidence and clinical implications with the use of DPI in patients with atherosclerotic disease.The implementation of a DPI by adding the so-called "vascular dose of rivaroxaban" (i.e., 2.5 mg bis in die), on top of antiplatelet therapy has consistently been associated with reduced levels of thrombin generation in PD studies and with reduced ischemic event rates at the cost of increased bleeding compared to antiplatelet therapy alone. Further research is warranted to best define patients in whom a DPI regimen has the best safety and efficacy profile.

INTRODUCTION AND OBJECTIVES The DECADE cooperation is a pooled analysis of individual patient data from drug-eluting stent (DES) trials with a 10-year follow-up. This analysis reports the risk of definite stent thrombosis (ST) through to 10 years after percutaneous coronary intervention (PCI) in patients treated with early- and new-generation DES. METHODS Individual patient data from 5 DES trials with a 10-year follow-up were pooled. The primary endpoint was definite ST up to 10 years after PCI. Patients were divided into 2 groups as per the generation of DES implanted (early and new DES). Individual participant data were analyzed using a 1-stage approach. RESULTS We included 9700 patients, 6866 in the new DES group and 2834 in the early DES group. Through to 10 years, definite ST occurred in 69 of 6866 patients treated with new DES and in 91 of 2834 patients treated with early DES (1.0% vs 3.5%, adjusted hazard ratio, 0.32; 95%CI, 0.23-0.45). The rate of definite ST was lower in the new DES group than in the early DES group from 1 to 5 years (rate ratio, 0.14; 95%CI, 0.08-0.26) and from 5 to 10 years (rate ratio, 0.23; 95%CI, 0.08-0.61) after PCI. CONCLUSIONS The incidence of definite ST through to 10 years after PCI with new-generation DES was 1%. New-generation DES are associated with a lower 10-year incidence of definite ST than early-generation DES, particularly beyond 1 year after PCI.

Background Coronary vascular function of a chronic coronary total occlusion (CTO) immediately after recanalization is known to be poor and to be partially improved by pre-treatment with loading dose of ticagrelor vs. clopidogrel . It is unknown if this vascular dysfunction is maintained at long-term follow-up and may be improved by 1-year dual antiplatelet therapy (DAPT). Methods The TIGER is a prospective, open-label, two parallel-group controlled clinical trial , which 1:1 randomized 50 CTO patients to pre-PCI loading dose and subsequent 1-year DAPT with ticagrelor vs. clopidogrel. Coronary blood flow (CBF) under stepwise adenosine infusion was assessed after drug loading dose and at follow-up and compared between the two drug groups, adjusting for time of follow-up. Results Out of 50 patients with index CBF evaluation, 38 (76%) patients underwent angiographic follow-up (23 and 15 at 1 and 3-year, respectively) and Doppler data was available in 35 (70%). A high CBF area under the curve (AUC), already observed after loading dose in ticagrelor vs. clopidogrel group (p = 0.027), was maintained at follow-up (AUC 34815.22 ± 24,206.06 vs. AUC 22712.47 ± 13,768.95; p = 0.071). Specifically, whereas high ticagrelor loading dose-related CBF was sustained at follow-up (p = 0.933), clopidogrel loading dose-related CBF increased at follow-up (p = 0.039). Conclusion The TIGER trial showed that DAPT with ticagrelor maintained a non-significantly higher CBF in a recanalized CTO as compared to clopidogrel, whose treated patients exhibit a lower CBF immediately after PCI with a significant increase at follow-up. The clinical value of such sustained high coronary flow should be evaluated in a larger group of patients. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT02211066 (ClinicalTrials.gov number NCT02211066 ).

Introduction and objectives The vasomotor function of new-generation drug-eluting stents designed to enhance stent healing and reendothelialization is unknown. This study aimed to compare the endothelial function of the infarct-related artery (IRA) treated with bioactive circulating endothelial progenitor cell-capturing sirolimus-eluting stents (COMBO) vs polymer-free biolimus-eluting stents (BioFreedom) in ST-segment elevation myocardial infarction patients at 6 months. Secondary objectives were to compare the microcirculatory function of the IRA and stent healing at 6 months. Methods Sixty patients were randomized to bioactive sirolimus-eluting stent vs polymer-free biolimus-eluting stents implantation. At 6 months, patients underwent coronary angiography with vasomotor, microcirculatory and optical coherence tomography examinations. Endothelial dysfunction of the distal coronary segment was defined as ≥ 4% vasoconstriction to intracoronary acetylcholine infusion. Results Endothelial dysfunction was similarly observed between groups (64.0% vs 62.5%, respectively; P = .913). Mean lumen diameter decreased by 16.0 ± 20.2% vs 16.1 ± 21.6% during acetylcholine infusion (P = .983). Microcirculatory function was similar in the 2 groups: coronary flow reserve was 3.23 ± 1.77 vs 3.23 ± 1.62 (P = .992) and the index of microcirculatory resistance was 24.8 ± 16.8 vs 21.3 ± 12.0 (P = .440). Optical coherence tomography findings were similar: uncovered struts (2.3% vs 3.2%; P = .466), malapposed struts (0.1% vs 0.3%; P = .519) and major evaginations (7.1% vs 5.6%; P = .708) were observed in few cases. Conclusions Endothelial dysfunction of the IRA was frequent and was similarly observed with new-generation drug-eluting stents designed to enhance stent reendothelialization at 6 months. Endothelial dysfunction was observed despite almost preserved microcirculatory function and complete stent coverage. Larger and clinically powered studies are needed to assess the role of residual endothelial dysfunction in ST-segment elevation myocardial infarction patients. Registered in ClinicalTrials.gov: NCT04202172

The aim of this communication is to consider the new problems that open-access models are posing for scholarly communication. Double charging, publishers with nonstandard practices, and biases associated with accessing the publishing market are some of the recent problems that the pay-to-publish model is producing. Taking these problems into account, this paper presents a proposal for combining the green and gold models, proposing a solution that could benefit the publishing system, separating it from the commercial sector. The article suggests the creation of journals through repositories, which would permit articles reviewed through open access, whose evaluation process would be supported by the same entities that fund them, to be published removed from commercial interests. The proposal is set out as a debatable idea that discusses the commercial nature of scientific publishing. Resumen La presente nota pretende hacer una reflexión sobre los nuevos problemas que el modelo open access está trayendo a la comunicación científica. Dobles imposiciones, editoriales con comportamiento no estándar y sesgos en el acceso al mercado de publicación son algunos de los recientes males que el modelo de pago por publicación está generando. A partir de ahí, se describe una propuesta que aúna las vías verde y dorada, proponiendo una solución que podría beneficiar al sistema de publicación desligándolo del sector comercial. El artículo propone la creación de revistas dentro de los repositorios, que permitan la publicación, lejos de los intereses comerciales, de artículos revisados en abierto e incentivados en los procesos de evaluación por los mismos entes que lo financian. La propuesta se plantea como una forma de debate sobre el carácter comercial de la publicación científica.

Zinc-enriched mesoporous bioactive glasses (MBGs) are bioceramics with potential antibacterial and osteogenic properties. However, few assays have been performed to study these properties in animal models. In this study, MBGs enriched with up to 5% ZnO were synthesized, physicochemically characterized, and evaluated for their osteogenic activity both in vitro and in vivo. The ZnO MBGs showed excellent textural properties despite ZnO incorporation. However, the release of Zn2+ ions inhibited the mineralization process when immersed in simulated body fluid. In vitro assays showed significantly higher values of viability and expression of early markers of cell differentiation and angiogenesis in a ZnO-content-dependent manner. The next step was to study the osteogenic potential in a sheep bone defect model. Despite their excellent textural properties and cellular response in vitro, the ZnO MBGs were not able to integrate into the bone tissue, which can be explained in terms of inhibition of the mineralization process caused by Zn2+ ions. This work highlights the need to develop nanostructured materials for bone regeneration that can mineralize to interact with bone tissue and induce the processes of implant acceptance, cell colonization by osteogenic cells, and regeneration of lost bone tissue.

En la actualidad, la formación profesional superior incide en el desarrollo de la educación de los países. Las tecnologías de aprendizaje en línea se están popularizando cada vez más en el sector de la educación no formal, universitario y complementaria. El blended learning, se ha vuelto cada vez más común en diferentes ámbitos del conocimiento, aprovechando las nuevas tecnologías y aumentando potencialmente la eficiencia y la flexibilidad de la enseñanza. El objetivo del presente estudio es identificar la producción científica sobre el blended learning y la formación profesional a nivel global en la base de datos de SCOPUS. Para ello, se identificaron un total de 154 documentos publicados entre el año 2005 y el 2021, recuperados de la base de datos SCOPUS. Los resultados presentan el análisis de indicadores bibliométricos de producción, visibilidad, impacto y colaboración. Se identificó un crecimiento paulatino y exponencial, siendo, la mayoría de tipo “Conferences and Proceedings”, el idioma predominante es el inglés. Los documentos más citados fueron realizados en su mayoría en el área de la salud. Los términos claves con mayor número de ocurrencias dentro de los 154 documentos fueron: blended learning, vocational education, teaching, e-learning, education, human, humans, students, vocational training y procedures.

Germline BRCA (gBRCA) mutations predispose to an increased risk of breast and ovarian cancer among other neoplasms. Recently, several genomic alterations such as ALK and ROS-1 rearrangements have been described as molecular drivers of venous thromboembolism (VTE). The association of gBRCA mutations and VTE is unknown. We performed an observational, retrospective, single-center study to determine the VTE incidence in consecutive patients with gBRCA mutations and cancer diagnosis attended in the multidisciplinary heredofamiliar cancer unit (HFCU) of Hospital General Universitario Gregorio Maranon, Spain, from 2010 to 2019. One-hundred and forty-one patients were included in the analysis. The overall VTE incidence was 12.8%. The highest incidence was reported in ovarian cancer patients (20.0%), followed by patients with both ovarian and breast cancers (16.6%) and the lowest was found in breast cancer (4.9%). No difference in the type of gBRCA mutation (1 or 2) in terms of VTE rate was observed. Sixty one percent of the patients were receiving anti-cancer therapy at the time of VTE diagnosis and the majority of the events (83.3%) were diagnosed in ambulatory setting. Khorana score was of limited value to detect high-risk patients. The VTE incidence observed in our study is consistent with prior data described in general population of breast and ovarian cancer. The risk of VTE in these patients seems to be driven by the type of cancer. We have not observed any significant interaction of gBRCA mutation status and cancer-associated thrombosis.

Objectives : To use the Consolidated Framework for Implementation Research (CFIR) adapted to a race-conscious frame to understand ways that structural racism interacts with intervention implementation and uptake within an equity-oriented trial designed to enhance student-school con­nectedness. Design: Secondary analysis of qualitative implementation data from Project TRUST (Training for Resiliency in Urban Students and Teachers), a hybrid effectiveness-imple­mentation, community-based participatory intervention. Setting: Ten schools across one urban school district. Methods: We analyzed qualitative ob­servational field notes, youth and parent researcher reflections, and semi-structured interviews with community-academic re­searchers and school-based partners within CFIR constructs based on framing questions using a Public Health Critical Race Praxis approach. Results: Within most CFIR constructs and sub-constructs, we identified barriers to implementation uptake not previously recognized using standard race-neutral definitions. Themes that crossed constructs included: 1) Leaders’ willingness to examine Black, Indigenous, People of Color (BIPOC) student and parent experiences of school discrimination and marginalization had a cascading influence on multiple factors related to implementation uptake; 2) The race/ethnicity of the principals was related to intervention engagement and interven­tion uptake, particularly at the extremes, but the relationship was complex; 3) External change agents from BIPOC communities facilitated intervention uptake in indirect but significant ways; 4) Highly networked implementation champions had the ability to enhance commitment to intervention uptake; however, perceptions of these indi­viduals and the degree to which they were networked was highly racialized. Conclusions: Equity-oriented interventions should consider structural racism within the CFIR model to better understand inter­vention uptake. Ethn Dis . 2021;31(Suppl 1):375-388; doi:10.18865/ed.31.S1.375

Aryl hydrocarbon receptor (AHR) interacting protein (AIP) is a chaperone which binds to inactive AHR in the cell cytoplasm. AHR is best known for mediating the toxicity of halogenated aromatics, but it has also been linked to carcinogenesis and tumor progression in several tumor types. Our aims are to assess the features of AIP immunohistochemical (IHC) staining and to evaluate its possible role as a prognostic marker in gastric cancer (GC). Retrospective study of 147 cases of resected GC. Clinicopathological features were collected, tissue microarrays were constructed for AIP IHC and statistical analysis were performed. AIP staining was observed in 50.3% of tumors. All AIP-positive cases exhibited cytoplasmic or membranous staining, variably associated with nuclear co-staining. 93.2% of AIP-positive tumors showed AIP immunoreactivity in 100% of cells. Staining intensity was mild, moderate and intense in 33.8%, 13.5% and 52.7% of cases. Tumors were stratified according to AIP staining intensity into low expression (no or mild AIP immunoreactivity) and high expression (moderate or intense AIP immunoreactivity). 36.6% of our cases showed high AIP expression. High AIP expression was significantly and independently correlated to tumor progression and cancer death. Tumors with high AIP expression showed lower survival and higher progression rates. AIP expression might be useful for determining GC prognosis. More studies are needed to clarify the role of AHR pathway in GC, AIP expression and its potential use as a surrogate marker for selecting patients for AHR modulation therapy.

El siguiente estudio propone identificar uno de los pigmentos más característicos del valle de Cañete durante el período Horizonte Medio, específicamente, el color verde amarillento observado en el repertorio cerámico de Cerro de Oro. Definir el origen y utilización de este pigmento facilita el entendimiento de la obtención de materia prima y cadena operativa en la elaboración de una de las cerámicas que definen a este desarrollo regional. Para este análisis se han utilizado como muestras, cerámicas con pigmento verdoso y muestras de rocas con restos de un mineral verdoso, halladas ambas en el sitio arqueológico de Cerro de Oro. Para definir la composición química y mineralógica, se han llevado a cabo análisis de FRX, Raman y DRX. A partir de estos análisis, se ha podido determinar que el mineral encontrado es epidota y su comportamiento a altas temperaturas parece indicar que este mineral podría estar relacionado con el pigmento encontrado en las cerámicas del sitio.

MicroRNAs (miRNA) are major regulators of intercellular communication and key players in the pathophysiology of cardiovascular disease. This study aimed to determine the miRNA fingerprint in a cohort of 53 patients with acute myocardial infarction (AMI) with non-ST-segment elevation (NSTEMI) relative to miRNA expression in healthy controls (n = 51). miRNA expression was initially profiled by miRNA array in the serum of patients undergoing cardiac catheterization during NSTEMI (n = 8) and 1 year past the event (follow-up, n = 8) and validated in the entire cohort. In total, 58 miRNAs were differentially expressed during AMI (p < 0.05), while 36 were modified at follow-up (Fisher’s exact test: p = 0.0138). Enrichment analyses revealed differential regulation of biological processes by miRNA at each specific time point (AMI vs. follow-up). During AMI, the miRNA profile was associated mainly with processes involved in vascular development. However, 1 year after AMI, changes in miRNA expression were partially related to the regulation of cardiac tissue morphogenesis. Linear correlation analysis of miRNA with serum levels of cytokines and chemokines revealed that let-7g-5p, let-7e-5p, and miR-26a-5p expression was inversely associated with serum levels of pro-inflammatory cytokines TNF-α, and the chemokines MCP-3 and MDC. Transient transfection of human endothelial cells (HUVEC) with let-7e-5p inhibitor or mimic demonstrated a key role for this miRNA in endothelial function regulation in terms of cell adhesion and angiogenesis capacity. HUVEC transfected with let-7e-5p mimic showed a 20% increase in adhesion capacity, whereas transfection with let-7e-5p inhibitor increased the number of tube-like structures. This study pinpoints circulating miRNA expression fingerprint in NSTEMI patients, specific to the acute event and changes at 1-year follow-up. Additionally, given its involvement in modulating endothelial cell function and vascularization, altered let-7e-5p expression may constitute a therapeutic biomarker and target for ischemic heart disease.

In recent decades, the life expectancy of HIV-infected patients has increased considerably, to the extent that the disease can now be considered chronic. In this context of progressive aging, HIV-infected persons have a greater prevalence of comorbid conditions. Consequently, they usually take more non-antiretroviral drugs, and their drug therapy are more complex. This supposes a greater risk of drug interactions, of hospitalization, falls, and death. In the last years, deprescribing has gained attention as a means to rationalize medication use. Review of the different therapeutic approach that includes optimization of polypharmacy and control and reduction of potentially inappropriate prescription. There are several protocols for systematizing the deprescribing process. The most widely used tool is the Medication Regimen Complexity Index, an index validated in HIV-infected persons. Anticholinergic medications are the agents that have been most associated with major adverse effects so, various scales have been employed to measure it. Other tools should be employed to detect and prevent the use of potentially inappropriate drugs. Prioritization of candidates should be based, among others, on drugs that should always be avoided and drugs with no justified indication. The deprescribing process shared by professionals and patients definitively would improve management of treatment in this population. Because polypharmacy in HIV-infected patients show that a considerable percentage of patients could be candidates for deprescribing, we must understand the importance of deprescribing and that HIV-infected persons should be a priority group. This process would be highly feasible and effective in HIV-infected persons.

RESUMEN Introducción: la evaluación del nivel de satisfacción de los pacientes dados de alta es uno de los métodos para medir la calidad de la atención en salud. Objetivos: determinar el nivel de satisfacción de los pacientes egresados del Servicio de Clínica Médica del Hospital Nacional (Itauguá, Paraguay) en agosto y septiembre 2018. Metodología: se aplicó el cuestionario SERVQUAL a varones y mujeres con al menos 1 semana de internación, previo consentimiento informado. Este instrumento mide con 22 preguntas a las 5 dimensiones de la atención: tangibilidad, confiabilidad, capacidad de respuesta, seguridad y empatía. Se utilizó la escala de Likert de 6 puntos donde el 1 era el más insatisfecho y el 6 el más satisfecho. Resultados: fueron incluidos 116 pacientes, 50 varones y 66 mujeres, con edad media 46±14 y 39±12 años, respectivamente. La dimensión con mejor puntuación en el cuestionario SERVQUAL fue la seguridad (media 5,3±0,8) y la más baja fue la tangibilidad (media 4,6±0,9). Aplicando el punto de corte en el percentil 60 (5,35 puntos) se obtuvo una frecuencia de 39,6% de satisfacción. Conclusión: la frecuencia de satisfacción de los usuarios del Servicio de Clínica Médica fue 39,6%. ABSTRACT Introduction: The evaluation of the level of satisfaction of discharged patients is one of the methods to measure the quality of health care. Objectives: To determine the level of satisfaction of the patients discharged from the Medical Clinic Service of the National Hospital (Itauguá, Paraguay) in August and September 2018. Methodology: The SERVQUAL questionnaire was applied to men and women with at least 1 week of hospitalization, with prior informed consent. This instrument measures the 5 dimensions of attention: tangibility, reliability, responsiveness, security and empathy using 22 questions. The Likert scale of 6 points was used, where 1 was the most dissatisfied and 6 was the most satisfied. Results: One hundred sixteen patients were included, 50 men and 66 women, with mean age 46 ± 14 and 39 ± 12 years, respectively. The dimension with the highest score in the SERVQUAL questionnaire was safety (average 5.3±0.8) and the dimension with the lowest score was tangibility (average 4.6±0.9). Applying the cut-off point in the 60th percentile (5.35 points), a frequency of 39.6% satisfaction was obtained. Conclusion: The frequency of satisfaction of the users of the Medical Clinic Service was 39.6%.

We have developed an in vitro model for the evaluation of potential anticoccidial properties of novel compounds aimed to control chicken coccidiosis, a costly disease for the poultry industry. This disease is caused by protozoan parasites of the genus Eimeria (Apicomplexa), and it is mainly controlled by chemoprophylaxis with ionophores and chemical anticoccidials; however, there is an overall agreement about the limitation of these traditional drugs and the need to improve current methods of control. Anticoccidial activities of novel compounds is currently evaluated by expensive experiments that involve large numbers of chickens. The use of our in vitro model for the pre-screening of essential oils led to a reduction of 67% of the chickens used in the in vivo trials for validation. Eimeria parasites can only complete their life cycle in their animal host, therefore chickens are required for their propagation as they cannot be propagated in vitro. In this study, we describe how further optimisation of this in vitro model by miniaturisation can have an additional impact in reduction of the number of chickens used for the generation of parasite stocks for provision of the in vitro model. We have estimated that the use of one chicken could support the evaluation of 10 compounds with a 96-well plate format versus only two compounds with a 24-well plate format, which means an 80% reduction in chicken use. In this study we have proved that the miniaturisation into a 96-well plate format perfectly mimics the invasion and replication observed before in the 24-well plate format. In addition, the 96-well plate format has allowed the simultaneous pre-screening of higher numbers of anticoccidial drugs at different concentrations following streamlined protocols in a more cost-effective way, factors that are beneficial for a wider uptake of the model by other researchers investigating anticoccidial compounds.

The exact mechanisms leading to myocardial injury in the coronavirus disease 2019 (COVID-19) are still unknown. In this retrospective observational study, we include all consecutive COVID-19 patients admitted to our center. They were divided into two groups according to the presence of myocardial injury. Clinical variables, Charlson Comorbidity Index (CCI), C-reactive protein (CRP), CAC (COVID-19-associated coagulopathy), defined according to the ISTH score, treatment and in-hospital events were collected. Between March and April 2020, 331 COVID-19 patients were enrolled, 72 of them (21.8%) with myocardial injury. Patients with myocardial injury showed a higher CCI score (median (interquartile range), 5 (4–7) vs. 2 (1–4), p = 0.001), higher CRP values (18.3 (9.6–25.9) mg/dL vs. 12.0 (5.4–19.4) mg/dL, p ˂ 0.001) and CAC score (1 (0–2) vs. 0 (0–1), p = 0.001), and had lower use of any anticoagulant (57 patients (82.6%) vs. 229 patients (90.9%), p = 0.078), than those without. In the adjusted logistic regression, CRP, myocardial injury, CCI and CAC score were positive independent predictors of mortality, whereas anticoagulants resulted as a protective factor. Myocardial injury in COVID-19 patients is associated with inflammation and coagulopathy, resulting in a worse in-hospital prognosis. Treatment with anticoagulant agents may help to improve in-hospital outcomes.

The early detection of cervical cancer requires the implementation of molecular screening programmes for human papillomavirus (HPV). However, there are discrepancies in the optimization of screening protocols. The performance of 10 primary screening strategies based on molecular, cytological or combined techniques is now evaluated.A blind, prospective, and interventional study was designed in 1.977 35-year-old women. The molecular determination was carried out by the Cobas 4800 HPV platform. Cytological analysis were performed on the same samples without knowledge of the result of the molecular assay. All women in whom HPV-16/HPV-18 was detected or presented cytological alteration together with detection of other high-risk genotypes (HPVhr) were referred to colposcopy.The molecular assay detected the presence of HPVhr genotypes in 12.5% of the women, while only 8.1% of the cytologies were pathological. Among the patients referred to colposcopy, in 19.5% high-grade lesions were observed, being HPV-16 present in 65.3% of them. In six of these high-grade lesions (associated with HPV-16 in all cases), cytology was reported as normal. The follow-up one year later, of women with normal cytology and HPVhr detection a HSIL/CIN2+ lesion was detected (associated to HPV-33). In the comparative study with other strategies, the protocol called CRYGEN 16/18 yielded the best balance of sensitivity and specificity with the least referral to colposcopy.Performing molecular detection of HPVhr with partial first-line genotyping of at least HPV-16, with direct referral to colposcopy, increases the detection rate of HSIL/CIN2+ lesions.

BACKGROUND: Participatory action research (PAR) empowers youth and parent stakeholders to address school connectedness and school environment inequities to improve educational social determinants of health. OBJECTIVES: To identify lessons learned when implementing school-based youth and parent PAR (YPAR and PPAR) targeting health and academic outcomes for Indigenous students and students of color. METHODS: We collected data from five community-academic research team members who coordinated YPAR and PPAR implementation across five middle and high schools and used thematic analysis with deductive and inductive coding to identify contributors to successful PAR implementation. RESULTS: Experiential learning strengthened youth and parent researcher skills and maintained their engagement, community-building supported the PAR process, PAR required support from facilitators with diverse skill sets, and individuals in bridging roles positioned researchers for success within institutions. CONCLUSIONS: PAR holds promise for application in other settings to address institutional change and social determinants of health.

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p

Introduction Gastric cancer (GC) shows high recurrence and mortality rates. The AJCC TNM staging system is the best prognostic predictor, but lymph node assessment is a major source of controversy. Recent studies have found that lymph node ratio (LNR) may overcome TNM limitations. Our aim is to develop a simplified tumor-LNR (T-LNR) classification for predicting prognosis of resected GC. Methods Retrospective study of all GC resected in a tertiary center in Spain (N = 377). Clinicopathological features were assessed, LNR was classified into N0:0%, N1:1–25%, N2:>25%, and a T-LNR classification was developed. Statistical analyses were performed. Results 317 patients were finally included. Most patients were male (54.6%) and mean age was 72 years. Tumors were intestinal (61%), diffuse (30.8%) or mixed (8.1%). During follow-up, 36.7% and 27.4% of patients progressed and died, respectively. T-LNR classification divided patients into five prognostic categories (S1-S5). Most cases were S1-S4 (26.2%, 19.9%, 22.6% and 23.6%, respectively). 7.6% of tumors were S5. T-LNR classification was significantly associated with tumor size, depth, macroscopical type, Lauren subtype, signet ring cells, histologic grade, lymphovascular invasion, perineural infiltration, infiltrative growth, patient progression and death. Kaplan-Meier curves for OS showed an excellent patient stratification with evenly spaced curves. As for DFS, T-LNR classification also showed good discriminatory ability with non-overlapping curves. T-LNR classification was independently related to both OS and DFS. Conclusions T-LNR classifications can successfully predict prognosis of GC patients. Larger studies in other geographic regions should be performed to refine this classification and to validate its prognostic relevance.

Introduction Gastric cancer (GC) is a multifactorial disease. Several prognostic scores have been proposed for refining the prognostic information provided by the TNM classification. Our aim is to validate and compare the prognostic performance of different clinicopathological scores in a western cohort of patients (Marubini, Haraguchi and Kologlu scores). Material and methods Retrospective study of all cases of GC resected in a western tertiary center (N = 377). Clinicopathological features were collected, scores were applied and statistical analyses were performed. Results 315 cases were finally included. According to Marubini, Haraguchi and Kologlu scores, patients were stage I (18.5%, 13.3% and 49%), II (29.3%, 47.2% and 29.5%) and III (52.2%, 39.5% and 21.5%, respectively). All classifications were significantly associated with lymphovascular invasion, perineural infiltration, lymph node involvement, patient progression and death due to GC. All scores showed good patient stratification by Kaplan-Meier analyses, but OS and DFS curves depending on Haraguchi score were less evenly spaced. Kologlu classification showed prognostic superiority over Haraguchi and Marubini classifications by ROC analysis. AUC values for OS and DFS were 0.654 and 0.647 (Marubini), 0.626 and 0.618 (Haraguchi) and 0.724 and 0.709 (Kologlu). Kologlu and Marubini classifications were independent factors for both OS and DFS, but Haraguchi classification was independently associated only with DFS. Conclusions Clinicopathological scores can be easily validated and are cost-effective. Kologlu score is the most thorough classification, and it showed the best prognostic performance for both DFS and OS in our study. More studies are needed to validate its value in other populations.

Home automation is known to systems that are capable of automating either a dwelling or a building that is too large, which implements many circuits providing energy services, safe and very reliable in what is communication, which are integrated into the interiors and exteriors of a building can be wired or wireless. The objective of the investigation is to determine how a user can prevent any emergency in which the building system fails and a situation in which it must be attended is prolonged, here are the technologists for providing good services and giving daily maintenance to prevent any emergency.That is why it is related between automation and intelligent control of housing that allows a very comfortable function as well as good energy savings and good communication between the user and the system, home automation allows to give knowledge of many devices electronic as is the sensors that collects information that is able to capture, process it and then issue an order to what are actuators or outputs, allows to respond to the requirements posed by these social changes in any house design or any building can be give a good comfort for the user that helps us in many ways in what is lighting, blinds, water etc.

Coronary percutaneous interventions have evolved from plain old balloon angioplasty (POBA) to stent implantation, which itself evolved from bare-metal stents (BMS) to the new biodegradable stents which try to restore endothelial function. Currently, the most commonly used stent is the everolimus-eluting stent.This review will cover the current status of durable polymer everolimus-eluting stent, its history, and future perspectives. Nowadays, the everolimus-eluting stent is the most used device in the acute and chronic settings due to its safety and efficacy.Durable polymer everolimus-eluting stent, supported by much evidence, has demonstrated its efficacy and safety, not only in de novo artery lesions, but in multiples scenarios, such as the acute setting and diabetic population, becoming one of the most polyvalent stents available. Nowadays, research is focused on the reduction of antiplatelet treatment duration. Similar rates of stent thrombosis with short dual antiplatelet treatment regimens of 1 to 3 months compared to pronged treatment have been observed. However, specific studies should be performed to evaluate this possibility.

P-element-induced wimpy testis (PIWI) proteins have been described in several cancers. PIWIL1 and PIWIL2 have been recently evaluated in pancreatic cancer, and elevated expression of PIWIL2 conferred longer survival to patients. However, PIWIL3&rsquo, s and PIWIL4&rsquo, s role in carcinogenesis is rather controversial, and their clinical implication in pancreatic cancer has not yet been investigated. In the present study, we evaluated PIWIL1, PIWIL2, PIWIL3 and PIWIL4 expression in pancreatic cancer-derived cell lines and in one non-tumor cell line as healthy control. Here, we show a differential expression in tumor and non-tumor cell lines of PIWIL3 and PIWIL4. Subsequently, functional experiments with PIWIL3 and/or PIWIL4 knockdown revealed a decrease in the motility ratio of tumor and non-tumor cell lines through downregulation of mesenchymal factors in pro of epithelial factors. We also observed that PIWIL3 and/or PIWIL4 silencing impaired undifferentiated phenotype and enhanced drug toxicity in both tumor- and non-tumor-derived cell lines. Finally, PIWIL3 and PIWIL4 evaluation in human pancreatic cancer samples showed that patients with low levels of PIWIL4 protein expression presented poor prognosis. Therefore, PIWIL3 and PIWIL4 proteins may play crucial roles to keep pancreatic cell homeostasis not only in tumors but also in healthy tissues.

Several classification systems have been described for stratifying patients with gastric carcinoma (GC). However, their prognostic value is low, and there is an urgent need for identification of molecular markers and development of new classifications. Retrospective study of 206 cases of GC diagnosed and surgically resected in our hospital between 2000 and 2017. Clinicopathological features of all cases were assessed and tissue microarrays were constructed for immunohistochemical (IHC) study. Patients were stratified based on IHC results. Mean patient age was 71 years and most patients were male (54.6%). Most tumors were located in the gastric antrum and body, and they were mostly fungoid or ulcerative lesions. GC were mainly intestinal-type tumors and 60.3% were diagnosed at pT3. 56.2% of patients showed recurrences and 29.4% died due to GC. According to our IHC classification, 23.5% of tumors showed microsatellite instability, 6% were E-cadherin negative, 53.5% were stable-p53 not overexpressed, and 17% were stable with p53 overexpression. IHC classification was significantly correlated with patient gender, gross morphology, Laurén classification, tumor necrosis, perineural infiltration, type of leading edge, and patient outcome. Multivariate analysis showed that IHC subtype was significantly and independently associated with overall survival, together with clinical symptoms, signet cell phenotype, tumor grade and vessel invasion. The application of IHC classifications based on molecular biomarkers in clinical practice can aid in the stratification of GC patients. More studies are needed to evaluate the reproducibility and clinical significance of these classifications.

Objective To analyze the changes in health-related quality of life (HRQoL) of patients with rheumatoid arthritis (RA) treated with biological therapies. Method Observational prospective study performed from October 2006 to May 2011. The inclusion criteria were adult patients, diagnosed with RA, treated for at least one year with anti-tumor necrosis factor therapy (infliximab or etanercept), who had not received other biological treatments previously. A total of 41 patients who completed the study undertook the specific and validated questionnaire QoL-RA Scale 3 times: E1 (September 2006–February 2007), E2 (April 2008–January 2009) and E3 (July 2010–May 2011). Data analysis was conducted using Epi-Info version 3.3 2004 for Windows® and Excel 2007; mean comparisons were evaluated by Student's t-test and the relationship between the 3 outcomes for each patient by lineal regression. Results Overall results show a downward trend which was not statistically significant: 7.09 (standard deviation [SD] = 1.15) in E1; 6.90 (SD = 1.60) in E2; and 6.52 (SD = 1.59) in E3. Items with higher scores were those related to psychosocial aspects (help from family, interaction with family and friends), whereas the physical dimension was valued more poorly (physical ability, arthritis pain, arthritis). Between E2 and E3 there was a significant increase in help from family (P = .0008), whereas level of tension (P = .0119) and mood (P = .0451) decreased significantly. Conclusions In all, HRQoL reported by patients is good and has remained unchanged after approximately 6 years of study. The stability of HRQoL is probably partly attributable to treatment.

Objectives To explore the role of ticagrelor versus clopidogrel in coronary blood flow normalization immediately after chronic coronary total occlusion (CTO) recanalization. Background Coronary vascular function of a CTO immediately after recanalization is demonstrated to be poor. Methods The TIGER BVS is a prospective, double-randomized, open-label, two parallel-group controlled clinical trial to evaluate efficacy of ticagrelor versus clopidogrel in improving vascular function of coronary segment distal to CTO immediately after CTO recanalization. A total of 50 patients who receive CTO PCI will be randomized 1:1 to receive ticagrelor versus clopidogrel at least 3 days before the procedure. Immediately after CTO recanalization with Absorb BVS implantation, a specific study of vascular function under adenosine infusion will be performed. Patients will be therefore randomized 1:1 to receive angiographic follow-up with vascular function and optical coherence tomography analyses at 1- or 3-year follow-up. This study is registered on ClinicalTrials.gov with number NCT02211066. Conclusions The TIGER BVS trial will provide the first randomized comparison between ticagrelor versus clopidogrel in recovering vascular function in CTO patients. It will also provide important data on vascular restoration therapy of Absorb BVS in this scenario.

The aim of this study is to know to what extent the Altmetric Attention Score ( AAScore ) can be reproduced. A sample of more than 28,000 research articles extracted from the public API of Altmetric.com were employed to reproduce the AAScore from the weights published in Altmetric.com. The indicator was correctly replicated in 13.2% of the cases, increasing the errors as the impact increases. The metrics that influence the most on the non-reproducibility are Tweeters (44%), news (16%) and blogs (12%). The main reason of this problem is the existence of non-published scoring criteria that impede the replication. This fact is an important limitation to the use of AAScore as research evaluation indicator.

Introduction: Although HAART cannot eradicate HIV, it suppresses viral replication, resulting in a progressive reduction in HIV-related morbidity and mortality. The increase in life expectancy for HIV-infected patients has turned this disease into a chronic disease and, therefore, to the appearance of comorbidities. At the same time there is an increase in the use of concomitant medication, making HIV-infected patient a polymedicated patient. Objective: To determine the degree of polypharmacy and to describe clinically relevant drug interactions, as well as the comorbidities and adherence to HAART in HIV + patients over 50 years. Methods: Observational, transversal study. Patients ≥50 years on HAART ambulatory were included. The variables were collected: aged, sex, VL, CD4, comorbidities, ARV, concomitant medication, herbal products and adherence. Patients who did not sign informed consent were excluded. Results: Were included 154 patients ≥50 years on HAART. The presence of polypharmacy, defined as the use of 5 or more medications including HAART, was 40.3%. 73.4% of the patients had concomitant medication: lipid-lowering agents (33.8%), anxiolytics / sedatives (28.6%), proton-pump inhibitors (26.0%) antihypertensive agents (23.4%). 102 relevant interactions were recorded, finding statistically significant differences in relation to the presence of polypharmacy and pharmacologic drugs classes (p

This article summarizes the clinical practice guide (CPG) for the evaluation and management of patients with severe aortic stenosis in the Social Security of Peru (EsSalud).To provide clinical evidence-based recommendations for the evaluation and management of patients with severe aortic stenosis in the EsSalud.A local guideline development group (local GDG) was established, including medical specialists and methodologists. The local GDG formulated 7 clinical questions to be answered by this CPG. Systematic searches of systematic reviews and, when it was considered pertinent, primary studies, were conducted in PubMed during 2018. The evidence to answer each of the posed clinical questions was selected. The quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic work meetings, the local GDG used the GRADE methodology to review the evidence and formulate the recommendations, points of good clinical practice, and the flowchart of evaluation and management. Finally, the CPG was approved with Resolution N.° 47 - IETSI - ESSALUD - 2018.This CPG addressed 7 clinical questions regarding two issues: the initial evaluation and the management of severe aortic stenosis. Based on these questions, 9 recommendations (1 strong recommendation and 8 weak recommendations), 16 points of good clinical practice, and 1 flowchart were formulated.This article summarizes the methodology and evidence-based conclusions from the CPG for the evaluation and management of patients with severe aortic stenosis in the EsSalud.El presente artículo resume la guía de práctica clínica (GPC) para la evaluación y el tratamiento de pacientes con estenosis aórtica severa en el Seguro Social del Perú (EsSalud).Proveer recomendaciones para la evaluación y el tratamiento de pacientes con estenosis aórtica severa en el EsSalud basadas en evidencia científica.Se conformó un grupo elaborador local (GEG-Local) que incluyó médicos especialistas y metodólogos. El GEG-Local formuló siete preguntas clínicas que ser respondidas en la presente GPC. Se realizaron búsquedas sistemáticas de revisiones sistemáticas y, cuando fue considerado pertinente, estudios primarios en PubMed durante el 2018. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas. La calidad de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG-Local usó la metodología GRADE para revisar la evidencia y formular las recomendaciones, los puntos de buenas prácticas clínicas y el flujograma de evaluación y tratamiento. Finalmente, la GPC fue aprobada con Resolución N.° 47 – IETSI – ESSALUD – 2018.La presente GPC abordó siete preguntas clínicas, respecto a dos temas: la evaluación inicial y el tratamiento de la estenosis aórtica severa. Con base en dichas preguntas se formularon nueve recomendaciones (una recomendación fuerte y ocho recomendaciones débiles), 16 puntos de buena práctica clínica y un flujograma.El presente artículo resume la metodología y las conclusiones de la GPC para la evaluación y el tratamiento de pacientes con estenosis aórtica severa en el EsSalud.

Pancreatic cancer is a highly aggressive manifestation of cancer, and currently presents poor clinical outcome due to its late diagnosis with metastasic disease. Surgery is the only approach with a curative intend, however, the survival rates seen in this type of patient are still low. After surgery, there is a lack of predictive prognosis biomarkers to predict treatment response and survival to establish a personalized medicine. Human P-element-induced wimpy testis 1 (PIWIL1) and P-element-induced wimpy testis 2 (PIWIL2) proteins act as protectors of germline, and their aberrant expression has been described in several types of tumors. In this study, we aimed to assess an association between PIWIL1 and PIWIL2 expression and the prognosis of biliopancreatic cancer patients. For this, we analyzed protein expression in complete resected tumor samples, and found a significant association between PIWIL2 expression and both progression-free and overall survival (p = 0.036 and p = 0.012, respectively). However, PIWIL2 expression was significantly associated with progression-free survival (p = 0.029), and overall survival (p = 0.025) of such tumors originated in the pancreas, but not in the bile duct or ampulla of Vater. Further analysis revealed that PIWIL1 and PIWIL2, at both mRNA and protein expression levels, correlated positively with factors associated to the progenitor molecular subtype of pancreatic cancer. Based on these findings, PIWIL1 and PIWIL2 expression may be considered a potential prognostic biomarker for resectable pancreatic cancer and may serve to guide subsequent adjuvant treatment decisions.

Introduction The TNM staging system is the main prognostic tool for GC, but the number of metastatic lymph nodes (LN) can be affected by surgical, pathological, tumor or host factors. Several authors have shown that lymph node ratio (LNR) may be superior to TNM staging in GC. However, cut-off values vary between studies and LNR assessment is not standardized. Material and methods Retrospective study of all GC resected in a western tertiary center (N = 377). Clinical features were collected and pathological features were assessed by two independent pathologists. Eight LNR classifications were selected and applied to our patients. Statistical analyses were performed. Results 315 patients were included. Most tumors were T3 (49.2%) N+ (59.3%). During follow-up, 36.7% of patients progressed and 27.4% died due to tumor. All LNR classifications were significantly associated with clinicopathological features such as Lauren subtype, lymphovascular invasion, perineural infiltration, T stage, tumor progression or death. All LNR classifications were independent prognostic factors for OS and DFS, and ROC analyses calculated similar AUC values for all staging systems. Kaplan-Meier curves showed that Pedrazzani, Wang, Liu and Huang classifications stratified patients better into three (Pedrazzani) or four categories. These classifications tended to downstage TNM N2 and N3 tumors. In cases with less than 16 LNs resected, Pedrazzani and Wang classifications showed the best prognostic performance. Conclusions Pedrazzani, Wang, Liu and Huang classifications showed good prognostic performance in western GC patients. Larger studies in other cohorts are needed to identify the most consistent LNR classification for GC.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Through specific base pairing with their targets messenger RNAs (mRNA), miRNA can modify cell phenotype and function. Several miRNAs are aberrantly expressed in diseased arteries and may influence different features of vascular remodeling, including neointimal formation and diminished re-endothelialization. This review will discuss the clinical implications of miRNAs in the field of vascular remodeling and their potential role as diagnostic and therapeutic tools. miRNA modulation offers a promising strategy for therapeutic intervention to inhibit smooth muscle cell proliferation and enhance endothelial regeneration after percutaneous coronary intervention (PCI) in order to reduce restenosis and late thrombosis.

Incomplete stent apposition (ISA) is related to stent thrombosis, which is a serious adverse event. We aim to assess the time-course of ISA after 2nd generation everolimus-eluting stent (EES) implantation.In HEAL-EES study, we enrolled 36 patients who underwent percutaneous coronary intervention (PCI) with EES. OCT imaging was performed at baseline and follow-up. Patients were randomized 1:1:1 into 3 groups according to the time in which follow-up was performed: group A (6-month), group B (9-month), and group C (12-month). In this subanalysis, patients who had ISA segments at baseline and/or follow-up OCT were analyzed.At baseline, among 41 lesions in 36 patients, 20 lesions in 18 patients had ISA segments and were analyzed. At baseline, there were 3.0% ISA struts in group A (n=8), 2.8% in group B (n=4), and 4.5% in group C (n=8). At follow-up, ISA struts were present in 0.09%, 0.16% and 0.64%; respectively in groups A, B, and C. At follow-up, there was a significant decrease in the frequency of ISA: group A 3.0% vs. 0.09% (p0.001), group B 2.8% vs. 0.16% (p0.001), and group C 4.5% vs. 0.64% (p0.001). In group A, there was one late acquired ISA at follow-up.In patients undergoing 2nd generation EES implantation, area of acute ISA assessed by OCT, was almost resolved at 6-month follow-up.

Objectives: To review our institutional experience and to analyze the clinical decisions made after a cytological diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS). Study Design: This is a retrospective review of all thyroid fine-needle aspiration (FNA) cytologies performed in the Hospital Clínico San Carlos (Madrid) between 2010 and 2014. Results: One hundred thirty thyroid FNA were categorized as AUS/FLUS (5%). One hundred six (81.5%) patients were women, and the mean age was 59 years. In 61 patients a repeated FNA was performed (46%). Fifty-five nodules were treated surgically (42.3%), with a histopathological diagnosis of nodular hyperplasia in 36 cases (65%), adenoma in 11 (20%), and carcinoma in 8 (14.5%). In the group of nonsurgical patients (n = 75), a repeated FNA was performed in 43 (57.3%) cases. We found no statistically significant association between sex or age and clinical management (p = 0.13 and p = 0.31, respectively). Conclusions: Clinical management after an AUS/FLUS FNA diagnosis is erratic and does not match standardized management protocols. The AUS/FLUS classification has not led to new diagnostic tests in a relevant percentage of patients. The implementation of consensual institutional strategies could lead to better management of these cases.

Background Mitotic count in hematoxylin-eosin stained slides and Ki-67 index allow stratification of patients for prognosis and therapeutic decision making in pancreatic neuroendocrine tumors (PNETs). However, the utility of Ki-67 determination in cytological material and its association to PNET prognosis are under discussion. Methods We have retrospectively reviewed all cases of EUS-FNA cytology of pancreatic lesions performed in the Hospital Clinico San Carlos (Madrid) between 2006 and 2016. We have analyzed the potential association between the Ki-67 estimation in PNET cytological material and patient outcomes. Results We identified 24 PNET cases. Mean age was 56.8 years and most patients were males (54%). PNETs were mainly located in the head and tail of the pancreas and the mean tumor size was 36 mm. Cell block from cytology was available in 12 cases (50%), and there were 19 G1, 2 G2, and 3 G3 tumors. All cases graded as G2 (2 patients) or G3 (three patients) on cytology were stage IV, and the 19 cases graded as G1 ranged from stages IA to IV. All patients with G2 tumors on cytology died due to PNET. Of the three patients with G3 lesions, two died of disease and the other died 2 months after diagnosis from causes other than PNET. 78% of the patients with G1 tumors are stable and currently being followed-up. Conclusion Higher Ki-67 index in cytology specimens portends a worse outcome, although some G1 tumors may progress or cause death. Diagn. Cytopathol. 2017;45:29-35. © 2016 Wiley Periodicals, Inc.

Neuroendocrine pancreatic tumors (PanNETs) are graded on the basis of their proliferative activity. Cytological samples are commonly the only samples available, but the determination of Ki-67 in cytology and its reliability as a measure of tumor mitotic activity is not well settled. We have retrospectively reviewed all the cases of FNA under EUS control of PanNETs in a 10-year period (2006-2016) in the Hospital Clínico San Carlos (Madrid). We identified 10 PanNET cases with histological correlation. Median age was 49.4 years and the patients were mainly women. PanNETs were located more frequently in the tail of the pancreas, with a median size of 33.8 mm. None of our cases was a grade 3 tumor. The seven grade 1 tumors confirmed in histology had consistent Ki-67 in cytology. In three cases (30 %), there were discrepancies between the Ki-67 index measured in cytology and histology, and the differences ranged from 2 to 15 %; all these cases were grade 2 tumors in histology and were graded as grade 1 tumors in FNA material. Our results are consistent with previous studies which showed understaging when tumor grade was assessed in cytological samples, mainly in G2 tumors. Previous literature has shown that Ki-67 assessment in EUS-FNA samples is a useful tool to rule out G3 tumors, but can be problematic for distinguishing G1 and G2 tumors.

Background Overlapping implantation of bioresorbable scaffolds (BRSs) are frequent in long coronary lesions. Its impact on clinical outcomes is unknown. Objective: To compare the clinical outcomes of patients treated with overlapping BRS with those patients treated with no-overlap BRS. Methods: We analyzed the 1-year clinical outcomes of 1,477 patients treated with BRS in the GHOST-EU registry, according to the implantation of overlapping BRS. Primary endpoint was patient oriented composite endpoint (PoCE) of: all-cause death, any myocardial infarction (MI) and any repeated revascularization. Scaffold thrombosis, according to Academic Research Consortium definition, was also analyzed. Results: A total of 320 (21.7%) patients were treated with overlapping BRS (overlap group), whereas the remaining 1,157 (78.3%) received no-overlap BRS (no-overlap group). The overlap group had significantly higher frequency of male sex, diabetes mellitus, stable angina, B2/C lesion type, SYNTAX score ≥22, lesion length >34 mm, use of intracoronary imaging guidance, pre- and postdilatation. At 1-year, there were no differences in PoCE between the overlap versus no-overlap group (18.4% vs. 18.2%; HR 1.07, [0.80–1.44]; P = 0.636), even after adjustment (HR 1.05, [0.48–2.20]; P = 0.904). Scaffold thrombosis rate did not differ either at one-month (1.3% vs. 1.5%, P = 0.769) or at 1-year (1.9% vs. 2.1%, P = 0.823). Conclusions: In “Real-world” clinical practice, overlapping BRS does not appear to have an impact on clinical outcomes as compared to no-overlapping BRS. These preliminary data should be confirmed. © 2016 Wiley Periodicals, Inc.

Designing nanocarriers for gene delivery is a multidisciplinary challenge that involves not only DNA condensation with biocompatible polymers, but also DNA-release processes. Once the genetic material is introduced into the cell, the rupture of degradable bonds permits the unpacking and release of the load. In this work, a dual-degradable polycation – composed by a linear poly(β-amino ester) chain in which ester and disulfide bonds coexist – has been used to condense a DNA plasmid. The goal was to reinforce the spontaneous hydrolysis of the ester groups with the intracellular break-up of the disulfide bonds, since these reducible bonds are degraded in the reductive intracellular environment. For a comparative study, two poly(β-amino ester) molecules differing only in the presence (or absence) of some S S bonds have been tested. DNA condensation, physico-chemical characterization of the polyplexes formed, and degradation studies have been carried out at pH 5 and pH 7. The acidic conditions gave the best nanoparticles, due to a better solubilization of both polymers and to a higher stability of the ester bonds. Despite the synthesis and storage of polyplexes were much more appropriate at pH 5, transfection efficiency in HeLa cells was similar irrespective the original pH used. Only in those polyplexes formed at low polymer:DNA ratios (i.e. 5 and 10 (w/w)) was transfection more effective when the plasmid was condensed at an acidic pH. With regard to the DNA-release efficiency in the intracellular medium, degradation of the polymers was practically governed by the rapid hydrolysis of the ester groups, this spontaneous and rapid process masking, unfortunately, any potential contribution associated with the breakup of the disulfide bonds.

For more than half a century, coronary angiography has been the gold standard diagnostic test for the assessment of coronary artery disease, but it does not provide information about the components of the vascular wall, atherosclerotic disease burden, or the interaction of local devices with coronary artery walls. The development of intracoronary imaging techniques, such as optical coherence tomography (OCT), was conceived with the objective to overcome coronary angiography limitations. Nonetheless, up-to-date OCT is more often used in the setting of research than in routine clinical practice [1]. In current clinical practice guidelines, OCT has limited indications for clinical applications [2]. However, many ongoing clinical trials are testing its utility for stent deployment optimization and stent follow-up [3]. (See Fig. 1.) In this issue of Cardiovascular Revascularization Medicine (CRM), Bogale et al. [4] address the use of OCT in the evaluation of intermediate coronary lesions. The authors conducted a retrospective analysis of patients, presenting to their center with non-ST-segment elevationmyocardial infarction (NSTEMI), who underwent coronary angiography and OCT imaging. A total of 36 patients were analyzed and classified as intermediate angiographic lesions (26 patients with stenosis 40%–69%) or severe angiographic lesions (10 patients with stenosis ≥70%), and OCT imaging of the suspicious culprit lesion was performed during the index procedure. In the OCT measurements analysis, authors found that angiographically intermediate lesions showed a larger minimal luminal area (MLA) and less severe percentage of lumen area stenosis when compared to angiographically severe lesions (3.3 mm ± 1.8 mm vs. 1.6 mm ± 0.6 mm, p b 0.001, and 54.2% ± 11.4% vs. 70.9% ± 6.8%, p = 0.001, respectively). Authors concluded that in stabilized patients with NSTEMI and angiographically intermediate disease, OCT examination confirmed the lack of severe anatomical stenosis in most patients. In a very appropriate manner, authors detailed the clinical data of the 26 patients inwhich OCT imagingwas performed. Although authors proposed the use of MLA threshold of ≤1.9 mm to determine the need of revascularization of intermediate lesions, operators seemed more prone to stenting because ofmorphological characteristics of the plaque (thrombus, rupture, and calcium nodules) or in case of positive cardiac biomarkers, rather than the actual MLA measurements. The report of the frequency in which OCT measurements changed physician decision-making would have been helpful, because it could be considered as an objective measure of the added value of performing the

Se analiza la evolucion de las principales redes sociales academicas: Mendeley , Academia.edu y ResearchGate . A traves de un seguimiento anual del numero de miembros y de documentos, se determina la salud actual de estas plataformas y en que fase de crecimiento se encuentran. Se discute el grado de transparencia de estos espacios a la hora de facilitar informacion sobre sus servicios. Los resultados muestran que estos sitios estan llegando a un punto de inflexion, donde se reducen sus indices de crecimiento y los ritmos de incorporacion de documentos y usuarios.

Two degradable poly(β-amino ester)s with an average molecular weight of 2 kDa, referred to as B1 and B2, have been synthesized to be tested as non-viral gene delivery systems. B2 polymer exhibits two additional non-polar ethyl groups at both ends. This paper describes the influence of that subtle difference on the compaction ability and temporal stability of the complexes formed with plasmid DNA. Our results suggest that the inclusion of those small hydrophobic fragments into the polycation backbone improves its suitability as synthetic DNA carrier. The improvement is related to the formation and physicochemical properties of the complexes. B2 polyplexes were more stable, the polymer hydrolysis was slowed down and plasmid DNA was better protected which was translated into better transfection efficiencies. Although still not totally understood, the role played by hydrophobic forces is ubiquitous in chemical, biological and physical systems, and they must be considered to design future polymers for gene delivery.

Aortic stenosis is highly prevalent in the elderly, when symptomatic, is associated with high mortality. Although its treatment is mainly surgical, cumulative evidence has demonstrated that transcatheter aortic valve implantation is an effective and safe treatment option for selected patients, especially for inoperable and high-risk patients. The aim of this review is to discuss the advances in current and emergent devices, with special focus on clinical and safety outcomes in randomized clinical trials and registries.

INTRODUCTION AND OBJECTIVES Cell-free DNA (cfDNA) in ST-segment elevation myocardial infarction might originate from hyperactivated leukocytes at the coronary lesion. Our aim was to investigate the relationship between cfDNA and coronary reperfusion. METHODS We studied 116 patients treated with primary angioplasty using thrombus aspiration. Coronary (during aspiration) and peripheral (at the end of the procedure) blood samples were drawn for cfDNA, as well as high-sensitivity troponin T and myeloperoxidase quantification. The primary endpoint was no ST-segment resolution (STR) (≥ 70%) and the secondary endpoint was lack of final Thrombolysis In Myocardial Infarction flow 3 (TIMI 3). RESULTS ST-segment resolution was achieved in 51 (44%) patients and TIMI 3 flow in 97 (84%). Patients without STR and TIMI 3 flow had a smaller peripheral-coronary cfDNA gradient (P = .02 and P = .04 respectively). A small cfDNA gradient (< 1.82 ng/mL) was associated with a higher rate of no STR (65% vs 30%; P = .001) and lack of TIMI 3 flow (21% vs 3%; P = .05). After multivariable adjustment, the small cfDNA gradient was predictive of no STR (OR, 4.50; 95%CI, 1.60-12.62; P = .004), while there was a nonsignificant trend for final TIMI 3 flow (P = .14). Cell-free DNA levels did not correlate with troponin T or myeloperoxidase. CONCLUSIONS A small peripheral-coronary cfDNA gradient, as an expression of high coronary cfDNA burden, is associated with no STR in acute myocardial infarction. Intracoronary cfDNA might reflect neutrophil activation. Whether this phenomenon contributes to thrombus aspiration failure requires further study.