Rendimiento diagnóstico de un nuevo software de aprendizaje profundo para corrección de atenuación en la imagen de perfusión miocárdica utilizando una cámara CZT cardiodedicada. Experiencia en la práctica clínica / Diagnostic performance of a novel deep learning attenuation correction software for MPI using a cardio dedicated CZT camera: Experience in the clinical practice

Objetivo Evaluar el rendimiento diagnóstico de un nuevo software de aprendizaje profundo para corrección de atenuación (SAPCA) en imágenes de perfusión miocárdica (IPM) utilizando una cámara cardiodedicada de cadmio-cinc-telurio (CZT) con correlación con angiografía coronaria (AC) para el diagnóstico de enfermedad arterial coronaria (EAC) en una población de alto riesgo. Métodos Estudio retrospectivo de 300 pacientes (196 varones [65%], edad media de 68 años) desde septiembre de 2014 hasta octubre de 2019. Posteriormente realizaron una IPM, seguida de AC dentro de los 6 meses posteriores a la IPM. La probabilidad media pretest para EAC según los criterios de la Sociedad Europea de Cardiología fue del 37%. La IPM se realizó en una cámara CZT cardio dedicada (D-SPECT® Spectrum Dynamics) usando un protocolo de 2 días, de acuerdo con las guías de la Sociedad Europea de Medicina Nuclear (EANM). La IPM fue evaluada con y sin el SAPCA. Resultados La precisión diagnóstica global de la IPM sin el SAPCA para identificar pacientes con cualquier EAC obstructiva en la AC fue del 87%, sensibilidad del 94%, especificidad del 57%, valor predictivo positivo del 91% y valor predictivo negativo del 64%. Utilizando el SAPCA, la precisión diagnóstica global fue del 90%, la sensibilidad del 91%, la especificidad del 86%, el valor predictivo positivo del 97% y el valor predictivo negativo del 66%. Conclusión El uso del novel SAPCA mejora el rendimiento diagnóstico de la IPM usando la cámara CZT D-SPECT®, especialmente reduciendo el número de resultados falsos positivos al reducir los artefactos (AU)

urpose To evaluate the diagnostic performance of a novel deep learning attenuation correction software (SAPCA) for myocardial perfusion imaging (MPI) using a cadmium-zinc-telluride (CZT) cardio dedicated camera with invasive coronary angiography (ICA) correlation for the diagnosis of coronary artery disease (CAD) in a high-risk population. Methods Retrospective study of 300 patients (196 males [65%], mean age 68 years) from September 2014 to October 2019 undergoing MPI, followed by ICA and evaluated by means of quantitative angiography software, within six months after the MPI. The mean pre-test probability score for coronary disease according to the European Society of Cardiology criteria was 37% for the whole cohort. The MPI was performed in a dedicated CZT cardio camera (D-SPECT® Spectrum Dynamics) with a two-day protocol, according to the European Association of Nuclear Medicine guidelines. MPI was retrospectively evaluated with and without the SAPCA. Results The overall diagnostic accuracy of MPI without SAPCA to identify patients with any obstructive CAD at ICA was 87%, Sensitivity 94%, Specificity 57%, positive predictive value 91% and negative predictive value 64%. Using SAPCA the overall diagnostic accuracy was 90%, sensitivity 91%, specificity 86%, positive predictive value 97% and negative predictive value 66%. Conclusion Use of the novel SAPCA enhances performance of the MPI using the CZT D-SPECT® camera and achieves improved results, especially avoiding artefacts and reducing the number of false positive results (AU)

Factores relacionados con la no adherencia a la rehabilitación cardiaca en pacientes con insuficiencia cardiaca / Factors related to non-adherence to cardiac rehabilitation in patients with heart failure

Introducción En la insuficiencia cardiaca (IC) se ha recomendado la rehabilitación cardiaca como estrategia de intervención que mejora la capacidad funcional, la calidad de vida relacionada con la salud y la supervivencia. No obstante, la adherencia a dichos programas es escasa. El objetivo fue determinar los factores relacionados con la no adherencia a la rehabilitación cardiaca en pacientes con IC en Colombia. Método Estudio observacional y retrospectivo. Se vincularon pacientes con IC en una clínica de Colombia, y la adherencia a la rehabilitación cardiaca se midió con ≥80% de las sesiones programadas. Se tuvieron en cuenta variables sociodemográficas, clínicas, capacidad aeróbica funcional (Sit to Stand y test de caminata de los 6minutos), Duke Activity Status Index (DASI), calidad de vida Minnesota Living with Heart Failure Questionnaire (MLFHQ) y depresión Patient health Questionnaire9 (PHQ-9). Resultados Se vincularon 300 pacientes con IC con edad 63,16±12,87; 194 (64,7%) eran hombres. La adherencia a la rehabilitación cardiaca fue del 66,67%, hubo diferencias estadísticamente significativas entre los grupos en la hipertensión arterial, FEVI, colesterol, LDL, triglicéridos, PAS, PAD, distancia recorrida, VO2e, METs, DASI y PHQ-9, p≤0,05. El modelo de regresión logística ajustado por sexo y edad mostró OR para la no adherencia a la RC: hipertensión arterial 2,23 [1,22-4,07], LDL fuera de metas 2,15 [1,20-3,88], triglicéridos fuera de metas 2,34 [1,35-4,07], DASI<4METs 2,38 [1,04-5,45] y PHQ-9 1,06 [1,00-1,12]. Conclusión La hipertensión arterial, LDL, triglicéridos, DASI y depresión con el cuestionario PHQ-9 son factores relacionados para no presentar adherencia a la rehabilitación cardiaca en pacientes con IC. (AU)

Introduction In heart failure, cardiac rehabilitation has been recommended as an intervention strategy that improves functional capacity, health-related quality of life and survival. However, adherence to these programs is low. The objective was to determine the factors related to non-adherence to cardiac rehabilitation in patients with heart failure in Colombia. Method Observational and retrospective study. Patients with heart failure were linked in a clinic in Colombia, adherence to cardiac rehabilitation was measured with ≥80% of scheduled sessions. Sociodemographic and clinical variables, functional aerobic capacity (Sit to Stand and 6-minute walk test), Duke Activity Status Index (DASI), quality of life Minnesota Living with Heart Failure Questionnaire (MLFHQ) and depression Patient health questionnaire 9 (PHQ-9) were taken into account. Results 300 patients were linked with heart failure with age 63.16±12.87; men 194 (64.7%). Adherence to cardiac rehabilitation was 66.67%, there were statistically significant differences between the groups in arterial hypertension, LVEF, cholesterol, LDL, triglycerides, SBP, DBP, distance traveled, VO2e, METs, DASI and PHQ-9 P≤.05. The logistic regression model adjusted for sex and age showed OR for non-adherence to CR arterial hypertension 2.23 [1.22-4.07], LDL outside of goals 2.15 [1.20-3.88], triglycerides outside goals 2.34 [1.35-4.07], DASI<4METs 2.38 [1.04-5.45] and PHQ-9 1.06 [1.00-1.12]. Conclusion High blood pressure, LDL, triglycerides, DASI and depression with the PHQ-9 questionnaire are related factors for not having adherence to cardiac rehabilitation in patients with heart failure. (AU)

Factores relacionados con la no adherencia a la rehabilitación cardiaca en pacientes con insuficiencia cardiaca / Factors related to non-adherence to cardiac rehabilitation in patients with heart failure

Introducción En la insuficiencia cardiaca (IC) se ha recomendado la rehabilitación cardiaca como estrategia de intervención que mejora la capacidad funcional, la calidad de vida relacionada con la salud y la supervivencia. No obstante, la adherencia a dichos programas es escasa. El objetivo fue determinar los factores relacionados con la no adherencia a la rehabilitación cardiaca en pacientes con IC en Colombia. Método Estudio observacional y retrospectivo. Se vincularon pacientes con IC en una clínica de Colombia, y la adherencia a la rehabilitación cardiaca se midió con ≥80% de las sesiones programadas. Se tuvieron en cuenta variables sociodemográficas, clínicas, capacidad aeróbica funcional (Sit to Stand y test de caminata de los 6minutos), Duke Activity Status Index (DASI), calidad de vida Minnesota Living with Heart Failure Questionnaire (MLFHQ) y depresión Patient health Questionnaire9 (PHQ-9). Resultados Se vincularon 300 pacientes con IC con edad 63,16±12,87; 194 (64,7%) eran hombres. La adherencia a la rehabilitación cardiaca fue del 66,67%, hubo diferencias estadísticamente significativas entre los grupos en la hipertensión arterial, FEVI, colesterol, LDL, triglicéridos, PAS, PAD, distancia recorrida, VO2e, METs, DASI y PHQ-9, p≤0,05. El modelo de regresión logística ajustado por sexo y edad mostró OR para la no adherencia a la RC: hipertensión arterial 2,23 [1,22-4,07], LDL fuera de metas 2,15 [1,20-3,88], triglicéridos fuera de metas 2,34 [1,35-4,07], DASI<4METs 2,38 [1,04-5,45] y PHQ-9 1,06 [1,00-1,12]. Conclusión La hipertensión arterial, LDL, triglicéridos, DASI y depresión con el cuestionario PHQ-9 son factores relacionados para no presentar adherencia a la rehabilitación cardiaca en pacientes con IC. (AU)

Introduction In heart failure, cardiac rehabilitation has been recommended as an intervention strategy that improves functional capacity, health-related quality of life and survival. However, adherence to these programs is low. The objective was to determine the factors related to non-adherence to cardiac rehabilitation in patients with heart failure in Colombia. Method Observational and retrospective study. Patients with heart failure were linked in a clinic in Colombia, adherence to cardiac rehabilitation was measured with ≥80% of scheduled sessions. Sociodemographic and clinical variables, functional aerobic capacity (Sit to Stand and 6-minute walk test), Duke Activity Status Index (DASI), quality of life Minnesota Living with Heart Failure Questionnaire (MLFHQ) and depression Patient health questionnaire 9 (PHQ-9) were taken into account. Results 300 patients were linked with heart failure with age 63.16±12.87; men 194 (64.7%). Adherence to cardiac rehabilitation was 66.67%, there were statistically significant differences between the groups in arterial hypertension, LVEF, cholesterol, LDL, triglycerides, SBP, DBP, distance traveled, VO2e, METs, DASI and PHQ-9 P≤.05. The logistic regression model adjusted for sex and age showed OR for non-adherence to CR arterial hypertension 2.23 [1.22-4.07], LDL outside of goals 2.15 [1.20-3.88], triglycerides outside goals 2.34 [1.35-4.07], DASI<4METs 2.38 [1.04-5.45] and PHQ-9 1.06 [1.00-1.12]. Conclusion High blood pressure, LDL, triglycerides, DASI and depression with the PHQ-9 questionnaire are related factors for not having adherence to cardiac rehabilitation in patients with heart failure. (AU)

Factors related to non-adherence to cardiac rehabilitation in patients with heart failure.

INTRODUCTION: In heart failure, cardiac rehabilitation has been recommended as an intervention strategy that improves functional capacity, health-related quality of life and survival. However, adherence to these programs is low. The objective was to determine the factors related to non-adherence to cardiac rehabilitation in patients with heart failure in Colombia. METHOD: Observational and retrospective study. Patients with heart failure were linked in a clinic in Colombia, adherence to cardiac rehabilitation was measured with ≥80% of scheduled sessions. Sociodemographic and clinical variables, functional aerobic capacity (Sit to Stand and 6-minute walk test), Duke Activity Status Index (DASI), quality of life Minnesota Living with Heart Failure Questionnaire (MLFHQ) and depression Patient health questionnaire 9 (PHQ-9) were taken into account. RESULTS: 300 patients were linked with heart failure with age 63.16 ± 12.87 men 194 (64.7%). adherence to cardiac rehabilitation was 66.67%, there were statistically significant differences between the groups in arterial hypertension, LVEF, cholesterol, LDL, Triglycerides, SBP, DBP, distance traveled, VO2e, METs, DASI and PHQ-9 p-value =<0.05. The logistic regression model adjusted for sex and age showed OR for non-adherence to CR arterial hypertension 2.23[1.22-4.07], LDL outside of goals 2.15[1.20-3.88], triglycerides outside goals 2.34[1.35-4.07], DASI<4METs 2.38 [1.04-5.45] and PHQ-9 1.06[1.00-1.12]. CONCLUSION: High blood pressure, LDL, triglycerides, DASI and depression with the PHQ-9 questionnaire are related factors for not having adherence to cardiac rehabilitation in patients with heart failure.

Habitat type drives the spatial distribution of Australian fish chorus diversitya).

Fish vocalize in association with life functions with many species calling en masse to produce choruses. Monitoring the distribution and behavior of fish choruses provides high-resolution data on fish distribution, habitat use, spawning behavior, and in some circumstances, local abundance. The purpose of this study was to use long-term passive acoustic recordings to obtain a greater understanding of the patterns and drivers of Australian fish chorus diversity at a national scale. This study detected 133 fish choruses from year-long recordings taken at 29 Australian locations with the highest fish chorus diversity identified at a site in the country's northern, tropical waters. A linear model fitted with a generalized least squares regression identified geomorphic feature type, benthic substrate type, and northness (of slope) as explanatory variables of fish chorus diversity. Geomorphic feature type was identified as the significant driver of fish chorus diversity. These results align with broad-scale patterns reported previously in fish biodiversity, fish assemblages, and fish acoustic diversity. This study has highlighted that passive acoustic monitoring of fish chorus diversity has the potential to be used as an indicator of fish biodiversity and to highlight habitats of ecological importance.

Rendimiento diagnóstico de diferentes protocolos de estrés cardiaco usados en imagen de perfusión miocárdica para el diagnóstico de enfermedad coronaria usando una cámara de cadmio-zinc-telurio con correlación con angiografía coronaria / Diagnostic performance of different cardiac stress protocols for myocardial perfusion imaging for the diagnosis of coronary artery disease using a cadmium-zinc-telluride camera with invasive coronary angiography correlation

Objetivo Evaluar el rendimiento diagnóstico de tres protocolos diferentes de estrés cardiaco utilizados en imagen de perfusión miocárdica (IPM), usando una cámara de cadmio-zinc-telurio (CZT) en correlación con angiografía coronaria (AC) para el diagnóstico de enfermedad arterial coronaria (EAC) en una población de alto riesgo. Métodos Estudio retrospectivo realizado en 263 pacientes (96 mujeres y 167 varones, edad media 68 años), de los cuales 119 realizaron una prueba de estrés con bicicleta (PEB), 113 una prueba de estrés farmacológica (PEF) y 31 una combinación de ambas (PEC), entre septiembre de 2014 y diciembre de 2018. Posteriormente realizaron una IPM, seguida de AC dentro de los seis meses posteriores a la IPM. La probabilidad preprueba media para EAC según los criterios de la Sociedad Europea de Cardiología fue de 36%. La IPM se realizó en una cámara CZT cardio dedicada (D-SPECT Spectrum Dynamics) con un protocolo de dos días, de acuerdo con las guías de la Asociación Europea de Medicina Nuclear (EANM). Resultados No se observaron diferencias significativas entre los diferentes protocolos de estrés en términos de precisión diagnóstica (PEB 85%, PEF 88%, PEC 84%). La exactitud diagnóstica general de IPM para identificar pacientes con cualquier EAC obstructiva en AC fue de 86%, sensibilidad de 93%, especificidad de 54%, VPP de 90% y VPN de 63%. Conclusión La cámara CZT D-SPECT logra resultados generales satisfactorios en el diagnóstico de la EAC, sin encontrar diferencias significativas en el rendimiento diagnóstico cuando la prueba de esfuerzo se realizó como PEB, PEF o PEC. (AU)

Purpose To evaluate the diagnostic performance of three different cardiac stress protocols for myocardial perfusion imaging (MPI) using a cadmium-zinc-telluride (CZT) camera with invasive coronary angiography (ICA) correlation for the diagnosis of coronary artery disease in a high risk population. Methods Retrospective study of 263 patients (96 women and 167 males, mean age 68 years) from which 119 patients performed a bicycle stress test (BST), 113 pharmacological stress test (PST) and 31 a combination of the two (CST) between September 2014 and December 2018. The patients then underwent myocardial perfusion imaging (MPI), followed by ICA and evaluated by means of quantitative angiography software, within six months after the MPI. The mean pre-test probability score for coronary disease according to the European Society of Cardiology criteria was 36% for the whole population. The MPI was performed in a dedicated CZT cardio camera (D-SPECT Spectrum Dynamics) with a two-day protocol, according to the European Association of Nuclear Medicine guidelines. Results No significant difference was observed between the three stress protocols in terms of diagnostic accuracy (BST 85%, PST 88% and CST 84%). The overall diagnostic accuracy of MPI to identify patients with any obstructive CAD at ICA was 86%, Sensitivity 93%, Specificity 54%, PPV 90% and NPV 63%. Conclusion The CZT D-SPECT camera achieves overall satisfactory results in the diagnosis of CAD, observing no significant differences in the diagnostic performance when the stress test was performed as a BST, PST or CST (AU)

Meta-analysis of pre-clinical studies on the effects of opioid receptor ligands on food intake, motivation, and choice.

The opioid receptors (OR) regulate food intake. Still, despite extensive pre-clinical research, the overall effects and individual contribution of the mu (MOR), kappa (KOR), and delta (DOR) OR subtypes to feeding behaviors and food intake remain unclear. To address this, we conducted a pre-registered systematic search and meta-analysis of rodent dose-response studies to evaluate the impact of central and peripheral administration of non-selective and selective OR ligands on intake, motivation, and choice of food. All studies had a high bias risk. Still, the meta-analysis confirmed the overall orexigenic and anorexigenic effects of OR agonists and antagonists, respectively. Our results support a larger orexigenic role for central MOR agonists among OR subtypes and that peripheral OR antagonists reduce motivation for and intake of preferred foods. In binary food choice studies, peripheral OR agonists selectively increase the intake of fat-preferred foods; in contrast, they did not increase the intake of sweet carbohydrate-preferred foods. Overall, these data support that OR regulation of intake, motivation, and choice is influenced by food macronutrient composition.

Natural products from plants targeting key enzymes for the future development of antidiabetic agents.

Covering: 2000 to January 2023Diabetes is a metabolic disease of serious concern nowadays, with a negative economic impact. In 2021, the International Diabetes Federation estimated that more than 537 million adults live with diabetes, causing over 6.7 million deaths in that year. Intensive scientific research on medicinal plants in the last 100 years reveals that herbal drugs have been an essential source of products for developing antidiabetic agents acting on different physiological targets. This review summarizes recent research from 2000 to 2022 on plant natural compounds affecting selected crucial enzymes (dipeptidyl peptidase IV, diacylglycerol acyltransferase, fructose 1,6-biphosphatase, glucokinase, and fructokinase) involved in glucose homeostasis. Enzyme-aimed treatments usually induce reversible inhibition, irreversible by covalent changes of the objective enzymes, or bind non-covalently but so tightly that their inhibition is irreversible. Depending on the binding site, these inhibitors could be orthosteric or allosteric; in any case, the desired pharmacological action is achieved. One crucial advantage of targeting enzymes in drug discovery is that the required assays are usually simple, using biochemical experiments capable of analyzing enzyme activity.

Innovative multiple nanoemulsion (W/O/W) based on Chilean honeybee pollen improves their permeability, antioxidant and antibacterial activity.

Beehive derivatives, including honeybee pollen (HBP), have been extensively studied for their beneficial health properties and potential therapeutic use. Its high polyphenol content gives it excellent antioxidant and antibacterial properties. Today its use is limited due to poor organoleptic properties, low solubility, stability, and permeability under physiological conditions. A novel edible multiple W/O/W nanoemulsion (BP-MNE) to encapsulate the HBP extract was designed and optimized to overcome these limitations. The new BP-MNE has a small size (∼100 nm), a zeta potential greater than +30 mV, and efficiently encapsulated phenolic compounds (∼82%). BP-MNE stability was measured under simulated physiological conditions and storage conditions (4 months); in both cases, stability was promoted. The formulation's antioxidant and antibacterial (Streptococcus pyogenes) activity was analyzed, obtaining a higher effect than the non-encapsulated compounds in both cases. In vitro permeability was tested, observing a high permeability of the phenolic compounds when they are nanoencapsulated. With these results, we propose our BP-MNE as an innovative solution to encapsulate complex matrices, such as HBP extract, as a platform to develop functional foods.

Presiones de la vía biliar en pacientes con y sin colelitiasis

Introducción: El reflujo de enzimas pancreáticas hacia la vía biliar extra-hepática y la vesícula biliar es un fenómeno anormal que tiene un rol en la litogénesis y carcinogénesis. Debido a que la presión de la vía biliar depende entre otros factores, de las presiones del esfínter de Oddi. La disfunción de éste se vería reflejada en presiones elevadas de la vía biliar en pacientes con colelitiasis. Objetivo: El objetivo de este estudio es el de medir las presiones de la vía biliar extra-hepática en pacientes con y sin colelitiasis y relacionarlas con la presencia de reflujo pancreáticobiliar. Material y Método: Se diseñó un estudio pros-pectivo de casos y controles. La muestra está constituida por todos los pacientes operados con gastrectomía total por cáncer gástrico estadios I y II durante 30 meses. La medida de resultado primaria fue establecer diferencias en las presiones de la vía biliar entre pacientes con y sin colelitiasis. Resultados: Las presiones de la vía biliar extra-hepática en pacientes con colelitiasis fueron más elevadas (16,9 mmHg) que en los pacientes sin colelitiasis (3,3 mmHg) (p < 0,0001). Estas presiones se correlacionan con la presencia de amilasa y lipasa en la bilis de la vesícula; se encontraron niveles elevados de enzimas pancreáticas en pacientes con colelitiasis (p < 0,0001). Conclusiones: Las presiones de la vía biliar en pacientes con colelitiasis fueron, significativamente, mayores comparadas con las presiones de la vía biliar en pacientes sin colelitiasis. En los pacientes con colelitiasis, la presión elevada de la vía biliar se asocia a la presencia de reflujo pancreáticobiliar.

Background: The reflux of pancreatic enzymes into the bile duct and the gallbladder is an abnormal phenomenon that plays a role in lithogenesis and carcinogenesis. Because the pressure of the common bile duct depends on the pressures of the sphincter of Oddi, its dysfunction would be reflected in an increase in the pressure of the common bile duct in patients with cholelithiasis. Aim: The objective of this study was to measure the pressures of the common bile duct in patients with and without cholelithiasis and to relate them to the presence of pancreatobiliary reflux. Material and Method: A prospective case-control study was designed. The universe was constituted by all patients undergoing total gastrectomy for gastric cancer stages I and II during 30 months. The primary outcome measure was to establish differences between common bile duct pressures in patients with and without cholelithiasis. Results: Common bile duct pressures in patients with gallstones showed a significant elevation (16.9 mmHg) compared to patients without gallstones (3.3 mm Hg) (p < 0.0001). These pressures correlated with the levels of amylase and lipase in gallbladder bile; higher levels were found in patients with gallstones compared to patients without gallstones (p < 0.0001). Conclusions: Common bile duct pressure in patients with cholelithiasis was significantly higher compared to patients without cholelithiasis leading to pancreatobiliary reflux.

Guía de recomendaciones para el manejo de brolucizumab / Guidance on brolucizumab management recommendations

Objetivo: Brolucizumab, un anti-VEGF de nueva generación, ha demostrado su eficacia y seguridad en la degeneración macular asociada a la edad neovascular exudativa (DMAEn) en los ensayos pivotales HAWK y HARRIER. Tras su comercialización, se han reportado eventos adversos relacionados con la inflamación intraocular no detectados previamente. Una revisión post hoc independiente de los ensayos pivotales cifra la tasa de inflamación intraocular (IIO) en el 4,6%. El objetivo de este trabajo es proponer una serie de recomendaciones para implementar el manejo de brolucizumab en la práctica clínica. Método: Las recomendaciones realizadas por los autores se han basado en su experiencia clínica y en la revisión crítica de: 1)los ensayos pivotales; 2)el análisis post hoc del Comité de Revisión de Seguridad, y 3)la literatura publicada. Resultados: En los ensayos pivotales, brolucizumab mostró ganancias funcionales sostenidas, resultados anatómicos superiores con intervalos entre inyecciones potencialmente más prolongados y un perfil de seguridad global bien tolerado. Los eventos adversos reportados tras la comercialización incluyen vasculitis retiniana y la oclusión vascular retiniana. De acuerdo con la información disponible, los expertos recomiendan: 1)descartar los perfiles de pacientes no recomendados (historial previo de IIO); 2)explorar al paciente antes de cada inyección para descartar la presencia de IIO activa; 3)monitorizar al paciente para detectar precozmente los signos de alerta, y 4)tratar de inmediato en el caso de que se desarrolle algún evento adverso. ConclusionesLos : eventos adversos reportados son poco frecuentes, pero pueden estar asociados con una pérdida severa e irreversible de agudeza visual. Las recomendaciones realizadas pretenden facilitar el manejo de brolucizumab en la práctica habitual de los retinólogos, garantizar la seguridad del paciente y, en caso de que se produzca alguno de los eventos adversos, minimizar su impacto sobre la visión. (AU)

Purpose: Brolucizumab, a new generation anti-VEGF, has demonstrated efficacy and safety in AMD in the pivotal HAWK and HARRIER trials. Post-marketing, previously undetected adverse events related to intraocular inflammation have been reported. An independent post hoc review of the pivotal trials puts the rate of intraocular inflammation (IOI) at 4.6%. The aim of this paper is to propose a set of recommendations for implementing the management of brolucizumab in clinical practice. Method: The recommendations made by the authors are based on their clinical experience and critical review of (i)the pivotal trials; (ii)the post-hoc analysis of the Safety Review Committee, and (iii)the published literature. Results: In the pivotal trials, brolucizumab showed sustained functional gains, superior anatomical outcomes with potentially longer intervals between injections and a well-tolerated overall safety profile. Adverse events reported post-marketing include retinal vasculitis and retinal vascular occlusion. Based on the available information, experts recommend (i)ruling out non-recommended patient profiles (prior history of ORI); (ii)screening the patient prior to each injection to rule out active IOI; (iii)monitoring the patient for early warning signs, and (iv)treating immediately should any adverse events develop. Conclusions: The adverse events reported are rare, but may be associated with severe and irreversible loss of visual acuity. The recommendations made are intended to facilitate the management of brolucizumab in the routine practice of retinologists, to ensure patient safety and, should any adverse events occur, to minimise their impact on vision. (AU)

Guidance on brolucizumab management recommendations.

PURPOSE: Brolucizumab, a new generation anti-VEGF, has demonstrated efficacy and safety in AMD in the pivotal HAWK and HARRIER trials. Post-marketing, previously undetected adverse events related to intraocular inflammation have been reported. An independent post hoc review of the pivotal trials puts the rate of IOI at 4.6%. The aim of this paper is to propose a set of recommendations for implementing the management of brolucizumab in clinical practice. METHODS: The recommendations made by the authors are based on their clinical experience, critical review of (i) the pivotal trials, the post-hoc analysis of the Safety Review Committee, (ii), and (iii) the published literature. RESULTS: In the pivotal trials, brolucizumab showed sustained functional gains, superior anatomical outcomes with potentially longer intervals between injections and a well-tolerated overall safety profile. Adverse events reported post-marketing include retinal vasculitis and retinal vascular occlusion. Based on the available information, experts recommend (i) ruling out non-recommended patient profiles (prior history of ORI), (ii) screening the patient prior to each injection to rule out active ORI, (iii) monitoring the patient for early warning signs, and (iv) treating immediately should any adverse events develop. CONCLUSIONS: The adverse events reported are rare, but may be associated with severe and irreversible loss of visual acuity. The recommendations made are intended to facilitate the management of brolucizumab in the routine practice of retinologists, to ensure patient safety and, should any adverse events occur, to minimise their impact on vision.

Anaerobic RSH-dependent tellurite reduction contributes to Escherichia coli tolerance against tellurite.

BACKGROUND: Tellurium is a rare metalloid that exerts high toxicity on cells, especially on bacteria, partly due to reactive oxygen species (ROS) generation. Moreover, it has also been observed that tellurite can target free cell thiols groups (RSH) (i.e. reduced glutathione (GSH)), enhancing the cellular redox imbalance. Additionally, in vitro experiments have suggested that several enzymes can reduce tellurite (IV) to its elemental form (0); where RSH present on their active sites may be responsible for the process. Nevertheless, the mechanisms implemented by bacteria for tellurite reduction and its role in resistance have not been evaluated in vivo. RESULTS: This work shows that tellurite reduction to elemental tellurium is increased under anaerobic conditions in E. coli cells. The in vivo tellurite reduction is related to the intracellular concentration of total RSH, in the presence and absence of oxygen. This metabolization of tellurite directly contributes to the resistance of the bacteria to the oxyanion. CONCLUSIONS: We demonstrated that in vivo tellurite reduction is related to the intracellular thiol concentration, i.e. large availability of cellular RSH groups, results in a more significant reduction of tellurite. Furthermore, we observed that, when the bacterium exhibits less resistance to the oxyanion, a decreased tellurite reduction was seen, affecting the growth fitness. Together, these results let us propose that tellurite reduction and the intracellular RSH content are related to the oxyanion bacterial resistance, this tripartite mechanism in an oxygen-independent anaerobic process.

Anaerobic RSH-dependent tellurite reduction contributes to Escherichia coli tolerance against tellurite

BACKGROUND: Tellurium is a rare metalloid that exerts high toxicity on cells, especially on bacteria, partly due to reactive oxygen species (ROS) generation. Moreover, it has also been observed that tellurite can target free cell thiols groups (RSH) (i.e. reduced glutathione (GSH)), enhancing the cellular redox imbalance. Additionally, in vitro experiments have suggested that several enzymes can reduce tellurite (IV) to its elemental form (0); where RSH present on their active sites may be responsible for the process. Nevertheless, the mechanisms implemented by bacteria for tellurite reduction and its role in resistance have not been evaluated in vivo. RESULTS: This work shows that tellurite reduction to elemental tellurium is increased under anaerobic conditions in E. coli cells. The in vivo tellurite reduction is related to the intracellular concentration of total RSH, in the presence and absence of oxygen. This metabolization of tellurite directly contributes to the resistance of the bacteria to the oxyanion. CONCLUSIONS: We demonstrated that in vivo tellurite reduction is related to the intracellular thiol concentration, i.e. large availability of cellular RSH groups, results in a more significant reduction of tellurite. Furthermore, we observed that, when the bacterium exhibits less resistance to the oxyanion, a decreased tellurite reduction was seen, affecting the growth fitness. Together, these results let us propose that tellurite reduction and the intracellular RSH content are related to the oxyanion bacterial resistance, this tripartite mechanism in an oxygen independent anaerobic process.

Influence of soil salinity on the protein and fatty acid composition of the edible halophyte Halimione portulacoides.

As the worldwide population continues to rise, so does global demand for agricultural production. This scenario of uncertain food supply is exacerbated by the high salinization of soils worldwide, a serious constraint to crop productivity. In this context, there is an increasing need for alternative sustainable crops. Halophytes are thought to be a promising alternative food source due to their natural ability to grow in saline soils and their multiple potential uses in the food industry. In this study, the protein and fatty acid content of the halophyte Halimione (Atriplex) portulacoides (L.) was studied in different saline conditions. Although more studies are needed to explore the nutritional properties of H. portulacoides, the data presented here suggest that this halophyte should be considered as a promising food crop for saline agriculture.

The effect of protease inhibitor-based dual antiretroviral regimens on CD4/CD8 ratio during the first year of therapy in ART-naïve patients with HIV-infection.

OBJECTIVES: To assess the effect of protease inhibitor (PI)-based dual therapy on CD4/CD8 ratio during the first year of therapy in antiretroviral therapy (ART)-naïve patients using data from randomized controlled clinical trials. METHODS: We pooled data from the GARDEL and ANDES studies, both randomized controlled clinical trials that recruited ART-naïve people living with HIV and randomly assigned them to receive PI-based dual therapy (DT) or triple therapy (TT) aiming to compare viral efficacy. We compared median CD4/CD8 ratios and the proportion of patients with CD4/CD8 ratio > 1 at 48 weeks after ART initiation in both treatment arms using the Mann-Whitney U-test and the χ2 test. We performed subgroup analysis for patients > 50 years old, with baseline CD4 counts ≤ 200 cells/µL, viral load > 100 000 HIV RNA copies/mL, and ritonavir-boosted lopinavir-based therapy. RESULTS: We analysed data from 571 patients: 292 on DT and 279 on TT. No differences were observed in CD4/CD8 ratio (0.632 vs. 0.617, P = 0.729) or in the proportion of patients with CD4/CD8 ratio > 1 (17.9% vs. 19.3%, P = 0.678) 48 weeks after ART initiation. Subgroup analysis showed no further differences. CONCLUSION: The impact of PI-based DT regimens on the CD4/CD8 ratio during the first year of treatment for ART-naïve patients is similar to that of TT.

Vitamin D and iron deficiencies in children and adolescents with cerebral palsy. / Deficiencia de vitamina D y de hierro en niños y adolescentes con parálisis cerebral.

INTRODUCTION: Children and adolescents with cerebral palsy (CP) are at a greater risk of malnutrition and micronutrient deficiencies. Two deficiencies that we can study and treat are vitaminD (VD) and iron deficiencies; however, no studies have described these deficiencies in Chile. OBJECTIVE: To describe the status of VD and iron in patients with CP and evaluate the relationship with certain factors associated with deficiencies of these micronutrients. PATIENTS AND METHOD: We performed a descriptive, cross-sectional study including 69 patients aged between 2 and 21years, from two public hospitals. Data were obtained on demographic variables, motor function, use of feeding tube, and pharmacological treatment. We performed a nutritional assessment according to patterns of CP and determined 25-hydroxyvitaminD (25[OH]D) ferritin, and albumin levels. RESULTS: Patients' mean age was 11.1±4.9years; 43 (62.3%) were male; and 56 (81.2%) had moderate-to-severe CP. Thirty-five (50.7%) used a nasogastric tube and/or gastrostomy; 15.4% were underweight and 73.8% were eutrophic, all with normal height. Twenty (29%) and 4 patients (6.2%) received VD and iron supplementation, respectively. Albuminaemia was normal in all patients. Mean 25(OH)D level was 24.3±8.8ng/mL; 33 patients (47.8%) had insufficiency and 21 (30.4%) deficiency; 36 patients (52.2%) had low ferritin levels. There was no association between 25(OH)D level and the other variables studied. Low ferritin levels were found to be associated with older age (P=.03), being male (P=.006), and feeding tube use (P=.006). CONCLUSIONS: The patients studied mainly had moderate-to-severe CP, with a high frequency of suboptimal VD values and low plasma ferritin; few patients received VD and/or iron supplementation. We suggest monitoring 25(OH)D and ferritin levels due to the high rate of deficiency of these nutrients; public hospitals should be equipped with drugs to treat these deficiencies.

A new standardised nomenclature in ophthalmology: Criteria and quantitative evaluation indicators of medical procedures. / Nuevo nomenclátor estandarizado en oftalmología: Criterios e indicadores cuantitativos de baremación de actos médicos.

PURPOSE: To create a new list of medical procedures in ophthalmology based on the International Classification of Diseases ICD-9-CM. To establish the general principles that define criteria, quantitative indicators, and scales. To develop the algorithms needed to calculate fees for medical procedures. METHODS: The out-of-date processes were removed from the list, and new techniques were added, descriptors were modified, procedures with similar descriptions were grouped together, and others were relocated to other group according to surgical complexity conditions. The criteria to calculate the medical fees were defined: training and complexity (U), proficient responsibility (R), and health value (V), with their respective quantitative indicators: period of training necessary to master a technique, frequency of complications that worsen the preoperative situation, and days of incapacity for work due to the process. The Relative Value Unit (RVU) was defined as the score sum of R, V and U. The final fee per medical procedure was calculated as the product of the RVU by its unit cost and by the weighting coefficient (WC). RESULTS: A new catalogue was prepared with 161 medical procedures, grouped into consultations, diagnostic procedures (DX.PR), therapeutic procedures (TX.PR), and surgical interventions, increasing in complexity from group 0 to group 8. The following characters were described for each one of the procedures: OMC and ICD-9-MC code, descriptor term, group, proposed modification: no changes or minimums in the descriptors, grouping of acts by similar definitions, change of origin group, new procedures, and procedures removed. The indicators for assessment were also scored: U between 1-4 points, and R and V between 0-3 points. Using their sum, the number of RVUs per medical procedure (between 1 and 10) was calculated which, together with the unit cost of the RVU and the WC (between 0.05 and 1), will determine the final rate. CONCLUSIONS: The new standardised ophthalmological nomenclature updates and improves the old classification, adapting the procedures to the descriptors included in the ICD-9-CM, and incorporating all the new techniques. Additionally, the declaration of the general principles allows defining new criteria, quantitative indicators, rating scales, and algorithms to calculate fees for medical procedures.