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Background. Left ventricle (LV) global longitudinal strain (GLS) at rest has shown prognostic value in patients (pts) with severe aortic stenosis (SAS). Contractile reserve (CR) during exercise stress echo (ESE) estimated via GLS (CR-GLS) could better stratify the asymptomatic patients who could benefit from early intervention. Aims. To determine the long-term prognostic value of CR-GLS in patients with asymptomatic SAS with an ESE without inducible ischemia. Additionally, to compare the prognostic value of CR assessed via ejection fraction (CR-EF) and CR-GLS. Methods. In a prospective, single-center, observational study between 2013 and 2019, 101 pts with asymptomatic SAS and preserved left ventricular ejection fraction (LVEF) > 55% were enrolled. CR was considered present with an exercise-rest increase in LVEF (Simpson's rule) >= 5 points and > 2 absolute points in GLS. Patients were assigned to 2 groups (G): G1: 56 patients with CR-GLS present; and G2: 45 patients CR-GLS absent. All patients were followed up. Results. G2 Patients were older, with lower exercise capability, less aortic valve area (AVA), a higher peak aortic gradient, and less LVEF (71.5% +/- 5.9 vs. 66.8% +/- 7.9; p = 0.002) and GLS (%) at exercise (G1: -22.2 +/- 2.8 vs. G2: -18.45 +/- 2.4; p = 0.001). During mean follow-up of 46.6 +/- 3.4 months, events occurred in 45 pts., with higher incidence in G2 (G2 = 57.8% vs. G1 = 42.2%, p < 0.01). At Cox regression analysis, CR-GLS was an independent predictor of major cardiovascular events (HR: 1.98, 95% CI 1.09-3.58, p = 0.025). Event-free survival was lower for patients with CR-GLS absent (log rank test p = 0.022). CR-EF was not outcome predictive (log rank test p 0.095). Conclusions: In patients with asymptomatic SAS, the absence of CR-GLS during ESE is associated with worse prognosis. Additionally, CR-GLS was a better predictor of events than CR-EF.

Background: The purpose of this work was to determine the influence of myocardial wringing on ventricular function in patients with cardiac amyloidosis (CA). Methods: Fifteen healthy volunteers (group 1) and 34 patients with CA (17 with left ventricular ejection fractions [LVEFs] >= 53% [group 2] and 17 with LVEFs < 53% [group 3]) were evaluated using two-dimensional speckletracking echocardiography. A control group of mass-matched patients (n = 20) with left ventricular (LV) hypertrophy and LVEFs >= 53% was also included. Longitudinal strain (LS), circumferential strain, and LV twist and torsion were calculated. Deformation index (DefI), a new parameter of wringing, calculated as twist/LS, that takes into account actions that occur simultaneously during LV systole (i.e., longitudinal shortening and twist), was evaluated. Torsional and wringing parameters were calculated according to LVEF. Results: Lower global values of LS and circumferential strain were observed among patients with CA (LS: group 1, -20.6 6 2.5%; group 2, -11.6 6 4.1%; group 3, -9.0 +/- 3.1%; circumferential strain: group 1, -22.7 +/- 4.9%; group 2, -14.4 +/- 8.0%; group 3, -13.6 +/- 3.8%; P

En el presente trabajo se describe la actividad larvicida de los aceites esenciales de Minthostachys mollis y Lepechinia bullata (Lamiaceae) contra Tecia solanivora una plaga que afecta a los cultivos de papa (Solanum tuberosum). Los aceites fueron obtenidos por hidrodestilación y su actividad biológica fue valorada por el método de papel impregnado o de contacto y fumigante para larvas. Los aceites esenciales de Minthostachys mollis y Lepechinia bullata pertenecientes a la familia Lamiaceae resultaron activos contra larvas de Tecia solanivora a las 24 h obteniéndose valores de CL50 de 0,020 µL/cm2 y 0,113 µL/cm2, respectivamente. La actividad observada en dichos aceites puede deberse a la presencia de los compuestos mayoritarios pulegona (55,2%) y trans-mentona (31,5%) presentes en el aceite esencial de Minthostachys mollis y ß-felandreno (14,9%) y premnaespirodieno (14,8%) para Lepechinia bullata, además puede deberse al efecto sinérgico de los diferentes componentes de estos aceites esenciales. En este sentido atendiendo la necesidad de buscar nuevos productos naturales con efecto larvicida, las especies Minthostachys mollis y Lepechinia bullata podrían representar una alternativa como agentes larvicidas. This work describes the larvicidal activity of Minthostachys mollis and Lepechinia bullata (Lamiaceae) essential oils against Tecia solanivora, a potato (Solanum tuberosum) crop pest. The oils were obtained by hydrodistillation and their biological activity was assessed by impregnated paper or contact and larvae fumigant methods. Minthostachys mollis and Lepechinia bullata essential oils were found to be active against Tecia solanivora after 24 h. The CL50 obtained were 0.020 µL/cm2 and 0.113 µL/cm2 respectively. The activity observed in these oils may be due to the presence of major compounds pulegone (55.2%) and trans-menthone (31.5%) present in Minthostachys mollis essential oil and ß-phellandrene (14.9%) and premnaespirodiene (14.8%) in Lepechinia bullata, thus, it also may be due to a synergistic effect between the different components of these essential oils. In this sense, taking into account the need of searching for newnatural products with larvicidal effect, Minthostachys mollis and Lepechinia bullata might represent an alternative as larvicidal agents. 19-24 rosslyn@ula.ve flormv@ula.ve ilka@gmail.com Semestral https://saber.ula.ve/farmacia/

Two case reports of advanced unresectable hepatocellular carcinoma (HCC) treated with lenvatinib (Lenvima®) are presented; the drug's effect on muscle loss and duration of treatment are discussed.Between November 2014 and December 2017, at the Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy, two male patients with advanced HCC enrolled in the lenvatinib arm of the REFLECT trial received the drug over 24 cycles (almost 2 years). We reviewed the clinical charts from baseline, when lenvatinib was started, through 24 months of treatment. The changes in the skeletal mass area (SMA), as assessed by computed tomography (CT) at the third lumbar level (L3), between baseline and month 24 into treatment were recorded.Case 1: SMA decreased by 2.8 cm2 between baseline and month 24 (134 cm2 vs. 131.2 cm2), with a muscle loss of 2.13%. Case 2: SMA decreased by 13 cm2 between baseline and month 24 (133 cm2 vs. 120 cm2), with a muscle loss of 10.83%.The disease remained stable for over 2.5 years in both patients. A minimal loss of muscle mass was noted at 24 months of treatment. The minimum effect on muscle loss may be correlated with the positive clinical response and the drug's low toxicity. Our findings may help to elucidate the effect of lenvatinib on muscle mass and inform the development of the targeted nutritional support for HCC patients.

Resumen Los estudio de cohortes (EC), son estudios de carácter longitudinal, observacional y analíticos. Corresponden a uno de los diseños más utilizados en investigación clínica, aportando altos niveles de evidencia, según el tipo de escenario en los que se aplique. Los EC tienen como objetivos, determinar asociación entre un factor de exposición y el desarrollo de alguna enfermedad o evento de interés, a partir de la estimación de riesgos; conocer la historia natural o el curso clínico de una enfermedad o de un evento de interés; determinar supervivencia; estudiar factores protectores y pronósticos. Los EC tienen diversas aplicaciones, por ejemplo: investigación de brotes epidemiológicos, estudios de causalidad, evaluación de intervenciones educacionales, etc. Teóricamente, la mejor aproximación es mediante un estudio de cohortes prospectivas; sin embargo, suelen exigir largos períodos de tiempo de seguimiento para obtener resultados útiles; por lo tanto, se puede recurrir a otras estrategias, como a los estudios retrospectivos y otros, que pueden resultar más factibles respecto de recursos y tiempos de seguimiento. El objetivo de este manuscrito fue generar un documento de estudio referente a descripción, metodología y aplicaciones de los EC en ciencias de la salud.

Resumen Las Guías de Práctica Clínica (GPC), son instrumentos adecuados para sistematizar la mejor evidencia científica disponible para colaborar con los clínicos en la toma de decisiones sanitarias. El objetivo de este artículo fue describir conceptos que permitan comprender la importancia de la utilización de las GPC en la práctica clínica cotidiana. En general, las GPC surgen de una serie de pasos que requieren distintos procedimientos dependiendo de la temática, entre los que destacan los aspectos metodológicos, la revisión sistemática de la literatura, la publicación e implementación, y la revisión y actualización periódica. Entre las ventajas de contar con GPC destaca el hecho de mejorar los resultados en salud debido a que su uso ayuda a promover acciones sanitarias adecuadas, reduciendo la variabilidad injustificada en la elección de tratamientos. Por otra parte, las GPC son instrumentos de gran utilidad para quienes deben planificar y gestionar gastos en salud, debido a que permiten mejorar la eficiencia de los recursos y controlar los costes sanitarios manteniendo la calidad asistencial. Entre las desventajas, se describen que con cierta frecuencia (y a pesar de todo) no logran cambiar una conducta, a menos que se acompañen de estrategias activas como sistemas de recordatorio, auditoria y retroalimentación, etc.; en parte, porque los profesionales de salud son resistentes a los cambios de comportamiento, ponen barreras de actitud en la aceptación de la validez de las recomendaciones, etc. Clinical Practice Guidelines (CPG) are useful tools to organize the best available scientific evidence, and to collaborate with clinicians in health decision making. The aim of this article was to describe concepts that allow understanding the importance of CPGs in daily clinical practice. CPGs arise from a series of steps that are carried out with varying intensity depending on the subject matter, among which are: methodological aspects, systematic review of the literature, publication and implementation, periodic review, and update. Among the advantages of CPGs is the improvement in health outcomes because its use helps to promote adequate health decision-making, reducing undue variability in the choice of treatments. On the other hand, PCs are very useful instruments for those who must plan and manage health costs, since they allow improving the efficiency of resources, and control health expenses while maintaining the quality of care. Among the disadvantages, it is described that eventually do not achieve to change a behavior, unless they are accompanied by active strategies such as reminder, audit and feedback systems, etc.; that physicians are resistant to behavioral changes, put attitude barriers in accepting the validity of recommendations, etc.

Resumen Las Guías de Práctica Clínica (GPC), son instrumentos adecuados para sistematizar la mejor evidencia científica disponible para colaborar con los clínicos en la toma de decisiones sanitarias. El objetivo de este artículo fue describir conceptos que permitan comprender la importancia de la utilización de las GPC en la práctica clínica cotidiana. En general, las GPC surgen de una serie de pasos que requieren distintos procedimientos dependiendo de la temática, entre los que destacan los aspectos metodológicos, la revisión sistemática de la literatura, la publicación e implementación, y la revisión y actualización periódica. Entre las ventajas de contar con GPC destaca el hecho de mejorar los resultados en salud debido a que su uso ayuda a promover acciones sanitarias adecuadas, reduciendo la variabilidad injustificada en la elección de tratamientos. Por otra parte, las GPC son instrumentos de gran utilidad para quienes deben planificar y gestionar gastos en salud, debido a que permiten mejorar la eficiencia de los recursos y controlar los costes sanitarios manteniendo la calidad asistencial. Entre las desventajas, se describen que con cierta frecuencia (y a pesar de todo) no logran cambiar una conducta, a menos que se acompañen de estrategias activas como sistemas de recordatorio, auditoria y retroalimentación, etc.; en parte, porque los profesionales de salud son resistentes a los cambios de comportamiento, ponen barreras de actitud en la aceptación de la validez de las recomendaciones, etc.

Type 2 diabetes (T2D) is a metabolic disorder characterized by hyperglycemia and insulin resistance in which oxidative stress is thought to be a primary cause. Considering that mitochondria are the main source of ROS, we have set out to provide a general overview on how oxidative stress is generated and related to T2D. Enhanced generation of reactive oxygen species (ROS) and oxidative stress occurs in mitochondria as a consequence of an overload of glucose and oxidative phosphorylation. Endoplasmic reticulum (ER) stress plays an important role in oxidative stress, as it is also a source of ROS. The tight interconnection between both organelles through mitochondrial-associated membranes (MAMs) means that the ROS generated in mitochondria promote ER stress. Therefore, a state of stress and mitochondrial dysfunction are consequences of this vicious cycle. The implication of mitochondria in insulin release and the exposure of pancreatic beta-cells to hyperglycemia make them especially susceptible to oxidative stress and mitochondrial dysfunction. In fact, crosstalk between both mechanisms is related with alterations in glucose homeostasis and can lead to the diabetes-associated insulin-resistance status. In the present review, we discuss the current knowledge of the relationship between oxidative stress, mitochondria, ER stress, inflammation, and lipotoxicity in T2D.

Aim Transient elastography (TE) is a rapid, non-invasive, reproducible assessment of liver fibrosis by liver stiffness measurement (LSM). Uncertainty remains regarding utility in children, unsedated and 2 years reliable results were obtained in ~80%. LSM increased with age; 0–2 years (3.5 ± 0.5 kPa), 3–5 years (3.8 ± 0.3 kPa) and 6–11 years (4.1 ± 0.2 kPa) with healthy older children 12–18 years similar to adults (4.5 ± 0.2 kPa). LSM did not vary with gender (female, 4.5 ± 0.2 vs. male, 4.8 ± 0.2 kPa). Children with intercurrent, non-hepatological illnesses had higher LSM (5.2 ± 0.2 kPa (range, 2.8–11.1 kPa)) compared to healthy children ((4.1 ± 0.1 kPa, range, 2.1–6.3 kPa); P = 0.0001). Conclusions TE in unsedated children is feasible from infancy but most reliable after 2 years. Intercurrent illness increases LSM; hence, study context is important when interpreting results.

Introduction Patients who are unable to fill prescriptions after discharge are at risk of hospital readmission. Ensuring that patients have prescriptions in hand at the time of discharge is a critical component of a safe and effective discharge process. Using a "Meds to Beds" program, we aimed to increase the percentage of patients discharged from Holtz Children's Hospital with medications in hand from 49% to 80%, reduce turnaround time (TAT) from electronic prescription signature to bedside delivery from 4.9 hours (±2.6 hours) to 2 hours, and increase caregiver satisfaction. Methods We formed a multidisciplinary team and implemented 4 patient-centered interventions through iterative plan-do-study-act cycles. Statistical process control charts were used to understand the impact of the interventions over 10 months. Hospital length of stay and discharges before 2:00 pm were used as balancing measures. We measured caregiver satisfaction using a telephone survey administered by pediatric residents within 7 days after discharge. Results The mean percentage of patients discharged with medications in hand increased to 76%. TAT decreased to 3.5 hours (±1.8 hours). Length of stay did not significantly increase, whereas the percentage of patients discharged before 2:00 pm did. Caregivers of patients who had prescriptions delivered to their bedside reported high levels of satisfaction. Conclusions Using a "Meds to Beds" program, we increased the percentage of patients discharged with medications in hand, decreased TAT with reduced variability, and achieved high levels of caregiver satisfaction. Importantly, there was a shift in the culture of the institution toward improved medication access for patients.

Background: Left ventricular ejection fraction (LVEF) results from the combined action of longitudinal and circumferential contraction, radial thickening, and basal and apical rotation. The study of these parameters together may lead to an accurate assessment of the cardiac function. Methods: Ninety healthy volunteers, categorized by gender and age ( 55 years), were evaluated using two-dimensional speckle tracking echocardiography. Transversal views of the left ventricle (LV) were obtained to calculate circumferential strain and left ventricular twist, while three apical views were obtained to determine longitudinal strain (LS) and mitral annular plane systolic excursion (MAPSE). We established the integral myocardial function of the LV according to: 1. The Combined Deformation Parameter (CDP), which includes Deformation Product (DP) - Twist x LS (degrees x %) - and Deformation Index (DefI) - Twist / LS (degrees / %)-; and 2. the Torsion Index (TorI): Twist / MAPSE (degrees / cm). Results: The mean age of our patients was 50.3 +/- 11.1 years. CDP did not vary with gender or age. The average DP was -432 +/- 172 degrees x %, and the average DefI was -0.96 +/- 0.36 degrees / %. DP provides information about myocardial function (normal, pseudonormal, depressed), and the DefI quotient indicates which component (s) is/are affected in cases of abnormality. TorI was higher in volunteers over 55 years (16.5 +/- 15.2 vs 13.1 +/- 5.0 degrees/cm, p=0.003), but did not vary with gender. Conclusions: The proposed parameters integrate values of twisting and longitudinal shortening. They allow a complete physiological assessment of cardiac systolic function, and could be used for the early detection and characterization of its alteration.

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