Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma.

The sub-ventricular zone (SVZ) is the most well-characterized neurogenic area in the mammalian brain. We previously showed that in 65% of patients with glioblastoma (GBM), the SVZ is a reservoir of cancer stem-like cells that contribute to treatment resistance and emergence of recurrence. Here, we built a single-nucleus RNA-sequencing-based microenvironment landscape of the tumor mass (T_Mass) and the SVZ (T_SVZ) of 15 GBM patients and 2 histologically normal SVZ (N_SVZ) samples as controls. We identified a mesenchymal signature in the T_SVZ of GBM patients: tumor cells from the T_SVZ relied on the ZEB1 regulatory network, whereas tumor cells in the T_Mass relied on the TEAD1 regulatory network. Moreover, the T_SVZ microenvironment was predominantly characterized by tumor-supportive microglia, which spatially co-exist and establish heterotypic interactions with tumor cells. Lastly, differential gene expression analyses, predictions of ligand-receptor and incoming/outgoing interactions, and functional assays revealed that the IL-1ß/IL-1RAcP and Wnt-5a/Frizzled-3 pathways are therapeutic targets in the T_SVZ microenvironment. Our data provide insights into the biology of the SVZ in GBM patients and identify specific targets of this microenvironment.

Género, infodemia y desinformación en salud. Revisión de alcance global, vacíos de conocimiento y recomendaciones.

OBJETIVO: explorar el estado de la literatura científica sobre los aspectos de infodemia y desinformación en salud vinculados al género y a la interseccionalidad, detectar vacíos de conocimiento y brindar recomendaciones. MÉTODOS: revisión de alcance global, con la detección de vacíos de conocimiento y recomendaciones. Se buscó en ocho bases de datos: MEDLINE (Pubmed), Anthropological Index Online, Studies on Women & Gender Abstracts, LILACS, Scielo, Global Index Medicus, Web of Science, Google académico y se hizo una búsqueda manual en Google de documentos de los últimos 10 años, sin restricciones de idioma y geográficas. Se realizó un análisis de contenido de los estudios incluidos. RESULTADOS: 855 registros fueron identificados y 21 cumplieron con los criterios de inclusión. Predominan los estudios que tuvieron como primer autor/a una mujer (13/21), aunque en la autoría global se destacaron los hombres (10/21). El modelo binario fue el enfoque principal (16/21). La mayoría (18/21) se publicaron a partir del 2020. Se abordaron principalmente temas relacionados con la COVID-19 y la salud sexual y reproductiva (antes de la pandemia), y en menor medida la salud mental. Se identificaron interacciones entre diferencias de sexo/género en la desinformación/infodemia en salud especialmente en mujeres, colectivos de género diverso, personas mayores y población de bajo nivel socioeducativo. CONCLUSIONES: existen brechas de conocimiento en el tema explorado, con escaso número de estudios, y limitaciones de alcances y del enfoque de género y/o feminista (más allá del binario). No obstante, los resultados tentativos constatan la presencia de inequidades de género e interseccionalidad en la desinformación en salud. PALABRAS CLAVE: infodemia, desinformación, género, COVID-19, revisión sistemática.

Adaptación cultural y propiedades psicométricas de la versión en español-chileno del cuestionario Family Satisfaction in the Intensive Care Unit – 24 item / Cultural adaptation and psychometric properties of the Chilean-Spanish version of the 24-item Family Satisfaction in the Intensive Care Unit questionnaire

Objetivo Adaptar y validar la versión en español del cuestionario 24-item Family Satisfaction in the Intensive Care Unit (FS ICU-24) en familiares de pacientes críticos en un hospital universitario en Chile. Diseño Estudio observacional, prospectivo, de adaptación y validación de un instrumento de medición. Ámbito Unidad de Cuidados Intensivos médico-quirúrgica de un hospital universitario en Chile. Pacientes o participantes Doscientos cuarenta familiares de pacientes críticos con estadía superior a 48h, mayores de 18 años y con al menos una visita al paciente. Intervenciones Ninguna. Variables de interés principales Se evaluó la validez de contenido, la validez de constructo y se realizó un análisis de confiabilidad de la versión en español del FS ICU-24. Resultados La versión en español del FS ICU-24 fue adaptada, mejorando su comprensión y claridad. El análisis factorial de la versión español-chilena del FS ICU-24 mostró una solución óptima de 3 factores, los cuales explican un 51% de la varianza total. La confiabilidad fue adecuada para la escala global (α=0,93) y las dimensiones de satisfacción con el cuidado del paciente y familia (α=0,82), satisfacción con la comunicación (α=0,91) y satisfacción con la toma de decisiones (α=0,71). Conclusiones La versión español-chilena del FS ICU-24 demostró ser válida y confiable para la evaluación de la satisfacción familiar en la Unidad de Cuidados Intensivos. El contar con un instrumento válido permitirá a las instituciones de salud objetivar e identificar posibles áreas de mejora en el cuidado de la familia y el paciente crítico (AU)

Objective To adapt and validate the Spanish version of the 24-item Family Satisfaction in the Intensive Care Unit (FS ICU-24) questionnaire among relatives of critically ill patients in a teaching hospital in Chile. Design Prospective observational study aimed to validate a measuring instrument. Setting Medical-surgical intensive care unit of a teaching hospital in Chile. Patients or participants Two hundred and forty relatives of critically ill patients with at least 48h in the ICU, older than 18 years, and with at least one visit to the patient. Interventions None. Main variables of interest Content validity, construct validity, and reliability analysis of the Spanish version of the FS ICU-24 were evaluated. Results The Spanish version of the FS ICU-24 was adapted, improving its understanding and clarity. The factor analysis showed an optimal solution of 3 factors for the Chilean-Spanish version of the FS ICU-24, which explain 51% of the total variance. Reliability was adequate for the global scale (α=0.93) and the dimensions of satisfaction with patient and family care (α=0.82), satisfaction with communication (α=0.91) and satisfaction with decision-making (α=0.71). Conclusions The Chilean-Spanish version of the FS ICU-24 proved to be valid and reliable for the evaluation of family satisfaction in the Intensive Care Unit. Having a valid instrument will allow health institutions to accurately identify areas for improvement in the care of the family members and the critically ill patient (AU}

Serotype b of Aggregatibacter actinomycetemcomitans triggers pro-inflammatory responses and amyloid beta secretion in hippocampal cells: a novel link between periodontitis and Alzheimer´s disease?

Introduction: Previous reports have proposed that Periodontal disease (PDis) predisposes to Alzheimer's disease (AD), both highly prevalent pathologies among the elderly. The bacteria Aggregatibacter actinomycetemcomitans (Aa), associated with the most aggressive forms of PDis, are classified in different serotypes with distinct virulence according to the antigenicity of their lipopolysaccharide (LPS). Methods: Here, we determined the effects of purified LPS, from serotypes a, b or c of Aa, on primary cultures of microglia or mixed hippocampal cells. Results: We found that both culture types exhibited higher levels of inflammatory cytokines (IL-1ß, IL-6 and TNFα) when treated with serotype b-LPS, compared with controls, as quantified by qPCR and/or ELISA. Also, cultures treated with serotype a-LPS displayed increased mRNA levels of the modulatory cytokines IL-4 and IL-10. Mixed hippocampal cultures treated with serotype b-LPS exhibited severe neuronal morphological changes and displayed increased levels of secreted Aß1-42 peptide. These results indicate that LPS from different Aa serotypes triggers discriminatory immune responses, which differentially affect primary hippocampal cells. Conclusion: Altogether, our results show that treatment with serotype b-LPS triggers the secretion of proinflammatory cytokines by microglia, induces neurite shrinking, and increases the extracellular Aß1-42 levels, all features strongly associated with the etiology of AD.

Composition dependent transport diffusion in non-ideal mixtures from spatially resolved nuclear magnetic resonance spectroscopy.

Nuclear magnetic resonance (NMR) spectroscopy is a well-established technique for the measurement of intra-diffusion coefficients. Recently, such information has been used as a basis of predictive models to extrapolate to the Fick diffusion coefficient of liquid mixtures. The present work presents a new approach to directly access the Fick diffusion coefficient by spatially resolved NMR experiments. The Fick diffusion coefficient of the binary mixture TEA/H2O was determined at two temperatures, 283.2 K and 275.2 K. The results are consistent with values previously reported either from optical experiments or predictive Darken-type models developed for this system. The proposed methodology adds high-resolution NMR to the toolbox for the study of the transport diffusion of multicomponent mixtures. It is, however, still limited to mixtures with liquid-liquid equilibrium phase separation.

Molecular Insight into the Liquid Propan-2-ol + Water Mixture.

The hydrogen bonding structure of the mixture propan-2-ol + water is analyzed at ambient conditions of temperature and pressure with molecular modeling and simulation techniques. A new force field for propan-2-ol is developed for this purpose on the basis of quantum chemical calculations and validated for a wide range of macroscopic properties. The basic mixing properties, excess volume and excess enthalpy, as well as the most important transport properties, that is, diffusion coefficients and shear viscosity, are considered to verify the suitability of the employed force fields for studying the complex behavior of this aqueous alcoholic mixture. Radial distribution functions and hydrogen bonding statistics are employed to characterize the hydrogen bond network and molecular clustering. Inhomogeneous mixing on the microscopic level, given by the presence of segregation pockets, is identified. The interrelation between the intriguing macroscopic behavior of this binary mixture and its microscopic structure is revealed.

Necesidades de los familiares de pacientes críticos en un hospital académico de Chile / Needs of relatives of critically ill patients in an academic hospital in Chile

Objetivo: Identificar el grado de importancia de las necesidades de los familiares de pacientes en una unidad de cuidados intensivos (UCI). Método: Estudio descriptivo, comparativo y transversal realizado a partir de un análisis secundario de datos de 251 familiares de pacientes de una UCI en un hospital universitario en Santiago, Chile. Utilizando un muestreo no aleatorio se aplicó el instrumento Critical Care Family Needs Inventory para conocer las necesidades familiares, además de un cuestionario sociodemográfico que incluyó: edad, género, nivel educacional, relación con el paciente y experiencia previa en UCI. Se realizó análisis estadístico descriptivo, prueba t de Student y ANOVA. Resultados: Las necesidades familiares más importantes se relacionaron con las dimensiones de «seguridad» (X¯=3,90) e «información» (X¯=3,76), mientras que las de menor importancia se relacionaron con la de «apoyo» (X¯=3,09). En esta última, se observaron diferencias a mayor edad (p<0,05), nivel educacional (p<0,001) y relación con el paciente (p<0,05). Conclusiones: Las necesidades más relevantes para los familiares en la UCI se relacionan con la seguridad e información. Las necesidades de menor importancia están influidas por ciertas variables sociodemográficas. La identificación del grado de importancia de las necesidades familiares permitirá al equipo de salud mejorar su relación con las familias en las UCI (AU)

Objective: To identify the importance of the needs of family members of patients in an intensive care unit (ICU). Method: Descriptive, comparative and cross-sectional study based on a secondary data analysis of 251 relatives of ICU patients at a university hospital in Santiago, Chile. Using non-random sampling, the 'Critical Care Family Needs Inventory' was used to establish the family needs, as well as a sociodemographic questionnaire that included: age, gender, educational level, patient relationship and previous ICU experience. A descriptive statistical analysis, Student's T test and ANOVA were performed. Results: The most important family needs related to the dimensions of 'security' (mean=3.90) and 'information' (mean=3.76), while those of minor importance with 'support' (mean=3.09). In the latter, differences were observed at an older age (P<.05), an educational level (P<.001) and relationship with the patient (P<.05). Conclusions: The most relevant needs for family members in the ICU are related to safety and information. Less important needs are influenced by certain sociodemographic variables. Identifying the degree of importance of family needs will allow the health team to improve its relationship with families in ICUs (AU)

Needs of relatives of critically ill patients in an academic hospital in Chile. / Necesidades de los familiares de pacientes críticos en un hospital académico de Chile.

OBJECTIVE: To identify the importance of the needs of family members of patients in an intensive care unit (ICU). METHOD: Descriptive, comparative and cross-sectional study based on a secondary data analysis of 251 relatives of ICU patients at a university hospital in Santiago, Chile. Using non-random sampling, the 'Critical Care Family Needs Inventory' was used to establish the family needs, as well as a sociodemographic questionnaire that included: age, gender, educational level, patient relationship and previous ICU experience. A descriptive statistical analysis, Student's T test and ANOVA were performed. RESULTS: The most important family needs related to the dimensions of 'security' (mean=3.90) and 'information' (mean=3.76), while those of minor importance with 'support' (mean=3.09). In the latter, differences were observed at an older age (P<.05), an educational level (P<.001) and relationship with the patient (P<.05). CONCLUSIONS: The most relevant needs for family members in the ICU are related to safety and information. Less important needs are influenced by certain sociodemographic variables. Identifying the degree of importance of family needs will allow the health team to improve its relationship with families in ICUs.

Generation of six multiple sclerosis patient-derived induced pluripotent stem cell lines.

Multiple sclerosis (MS) is considered a chronic autoimmune disease of the central nervous system that leads to gliosis, demyelination, axonal damage and neuronal death. The MS disease aetiology is unknown, though a polymorphism of the TNFRSF1A gene, rs1800693, is known to confer an increased risk for MS. Using retroviral delivery of reprogramming transgenes, we generated six MS patient-specific iPSC lines with two distinct genotypes, CC or TT, of the polymorphism rs1800693. iPSC lines had normal karyotype, expressed pluripotency genes and differentiated into the three germ layers. These lines offer a good tool to study MS pathomechanisms and for drug testing.

Understanding the Differing Fluid Phase Behavior of Cyclohexane + Benzene and Their Hydroxylated or Aminated Forms.

The three binary mixtures cyclohexane + benzene, cyclohexanol + phenol, and cyclohexylamine + aniline exhibit qualitatively different vapor-liquid phase behavior, that is, azeotropic with a pressure maximum, azeotropic with a pressure minimum, and zeotropic, respectively. Employing molecular modeling and simulation, the COSMO-SAC model, and a cubic equation of state, the root of these effects is studied on the basis of phase equilibria, excess properties for volume, enthalpy, and Gibbs energy as well as microscopic structure. It is found that cyclohexane + benzene is characterized by more pronounced repulsive interactions, leading to pressure maximum azeotropy and a positive excess Gibbs energy. Functionalizing the aliphatic and aromatic rings with one amine group each introduces attractive hydrogen bonding interactions of moderate strength that counterbalance such that the mixture becomes zeotropic. The hydroxyl groups introduce strong hydrogen bonding interactions, leading to pressure minimum azeotropy and a negative excess Gibbs energy.

Mutual diffusion of binary liquid mixtures containing methanol, ethanol, acetone, benzene, cyclohexane, toluene, and carbon tetrachloride.

Mutual diffusion coefficients of all 20 binary liquid mixtures that can be formed out of methanol, ethanol, acetone, benzene, cyclohexane, toluene, and carbon tetrachloride without a miscibility gap are studied at ambient conditions of temperature and pressure in the entire composition range. The considered mixtures show a varying mixing behavior from almost ideal to strongly non-ideal. Predictive molecular dynamics simulations employing the Green-Kubo formalism are carried out. Radial distribution functions are analyzed to gain an understanding of the liquid structure influencing the diffusion processes. It is shown that cluster formation in mixtures containing one alcoholic component has a significant impact on the diffusion process. The estimation of the thermodynamic factor from experimental vapor-liquid equilibrium data is investigated, considering three excess Gibbs energy models, i.e., Wilson, NRTL, and UNIQUAC. It is found that the Wilson model yields the thermodynamic factor that best suits the simulation results for the prediction of the Fick diffusion coefficient. Four semi-empirical methods for the prediction of the self-diffusion coefficients and nine predictive equations for the Fick diffusion coefficient are assessed and it is found that methods based on local composition models are more reliable. Finally, the shear viscosity and thermal conductivity are predicted and in most cases favorably compared with experimental literature values.

Polymorphisms in histone deacetylases improve the predictive value of IL-28B for chronic hepatitis C therapy.

Histone deacetylases (HDACs) influence many cellular processes, including the modulation of signal transducer and activator of transcription activity (STAT) in response to interferon (IFN). To identify genetic markers that help optimize the IL-28B prediction of chronic hepatitis C (CHC) sustained virological response (SVR), we evaluated 27 single-nucleotide polymorphisms (SNPs) in HDAC1-11. Three SNPs, rs3778216, rs976552 and rs368328 in HDAC2, HDAC3 and HDAC5, respectively, were independently associated with SVR (P<0.05). The addition of these three HDAC's SNPs to the IL-28B predictive model (area under the curve (AUC)=0.630) rendered an important improvement of AUC-receiver operating characteristic value (AUC=0.747, P=0.021). Chi-squared Automatic Interaction Detector (CHAID) analysis denoted the significance of the rs3778216 C/C genotype in identifying a group of good responders despite carrying IL-28B T allele (79.2% of SVR), whereas HDAC5 G allele characterized a subgroup with poor response rate (25.5%). However, HDAC3 rs976552 did not display a relevant role for the hierarchical classification of patients. Variables related to SVR in hepatitis C virus genotype 1 (HCV-1) cohort were the same of those obtained for the overall population. Interestingly, in non-HCV-1 patients (n=56) the HDAC2 C/C genotype was the unique predictive variable related to SVR (AUC=0.733, P<0.007). Thus, these preliminary results suggest the potential usefulness of combined IL-28B and HDAC genotyping for the CHC patients' classification by likelihood of an SVR.

Metabolism of dehydroepiandrosterone sulfate and estrone-sulfate by human platelets.

The aim of the present research was to study the uptake of DHEAS, and to establish the intracrine capacity of human platelets to produce sex steroid hormones. The DHEAS transport was evaluated through the uptake of [(3)H]-DHEAS in the presence or absence of different substrates through the organic anion transporting polypeptide (OATP) family. The activity of sulfatase enzyme was evaluated, and the metabolism of DHEAS was measured by the conversion of [(3)H]-DHEAS to [(3)H]-androstenedione, [(3)H]-testosterone, [(3)H]-estrone and [(3)H]-17beta-estradiol. Results indicated the existence in the plasma membrane of an OATP with high affinity for DHEAS and estrone sulphate (E(1)S). The platelets showed the capacity to convert DHEAS to active DHEA by the steroid-sulfatase activity. The cells resulted to be a potential site for androgens production, since they have the capacity to produce androstenedione and testosterone; in addition, they reduced [(3)H]-estrone to [(3)H]-17beta-estradiol. This is the first demonstration that human platelets are able to import DHEAS and E(1)S using the OATP family and to convert DHEAS to active DHEA, and to transform E(1)S to 17beta-estradiol.

Dehydroepiandrosterone prevents the aggregation of platelets obtained from postmenopausal women with type 2 diabetes mellitus through the activation of the PKC/eNOS/NO pathway.

The steroid hormone dehydroepiandrosterone (DHEA), suggested to be a cardioprotector, prevents platelet aggregation in healthy humans. This hormone is reduced in postmenopausal women by 60% of its normal value. Platelets in patients with type 2 diabetes (T2D) are more sensitive to aggregation, which has been attributed to a reduced ability to produce nitric oxide (NO). In light of these precedents and considering that DHEA is able to increase the production of NO in cultured endothelial cells, we suggest that DHEA prevents the aggregation of platelet from postmenopausal women with T2D through the activation of PKC/eNOS/NO/cGMP pathway. To determine the effect of DHEA in platelet aggregation, platelet-rich plasma (PRP) obtained from postmenopausal women with T2D was preincubated with DHEA, and aggregation induced by ADP was determined in the presence or absence of L-NNA (LNG-nitroarginine), Rottlerin, NOS, or PKC delta inhibitors, respectively. Platelet NO production was measured with the fluorescent probe DAF2DA and eNOS activation was determined by Western blot, using an anti-p-eNOS (ser 1177) antibody. DHEA 1) prevented platelet aggregation by 40% compared to control, 2) increased NO production by 63%, 3) increased p-eNOS (phosphorylated endothelial nitric oxide synthase) levels, and 4) increased cGMP production. These effects were reduced in the presence of L-NNA or Rottlerin. DHEA prevents platelet aggregation induced by ADP. This effect is mediated by the activation of the PKCδ/eNOS/NO/cGMP pathway. Our results suggest that DHEA could be considered to be a potential therapeutic tool in the prevention of atherothrombotic processes in postmenopausal women with T2D.

Genetic variants of interferon-stimulated genes and IL-28B as host prognostic factors of response to combination treatment for chronic hepatitis C.

Chronic hepatitis C (CHC) is a worldwide health problem that is highly related to liver fibrosis, cirrhosis, and hepatocellular carcinoma. The achievement of response to the current standard of care-pegylated interferon plus ribavirin-has recently been described to be associated with single-nucleotide polymorphisms (SNPs) near the IL-28B gene. Additionally, baseline expression levels of genes involved in interferon (IFN)-stimulated genes (ISGs) have been found to be related to treatment outcome. In the present study, 285 patients were genotyped for 63 SNPs within genes of the IFN signaling pathway (IPGs) and ISGs. Two ISG polymorphisms-OASL rs12819210 (odds ratio (OR)=2.1, P=0.03) and IFIT1 rs304478 (OR=2.5, P=0.01)-were found to be independent predictive factors of sustained virological response (SVR) after adjusting for other clinical covariates. Furthermore, the predictive value of IL-28B SNP was notably improved by simultaneous genotyping of rs12819210 and rs304478, particularly in patients with the worst prognosis (viral genotype 1, area under the curve (AUC)=0.74). In conclusion, ISG SNPs could constitute a valuable tool for individualizing CHC therapy.

La declaración de Helsinki sobre seguridad del paciente en anestesiología / No disponible

En Junio de 2010, los responsables de las sociedades científicas europeas en la especialidad de Anestesiología aprobaron la declaración sobre seguridad del paciente, denominada Declaración de Helsinki.. No es casual que los líderes de la especialidad acordaran una declaración en esta materia, pues la Anestesiología, a través de su historia, ha estado siempre especialmente concienciada con la gestión de los riesgos y la seguridad del paciente. Por otra parte, la transversalidad y el gran campo de acción en que el anestesiólogo desarrolla su actividad hacen que las prácticas seguras adquieran una especial relevancia en su trabajo y que éstas tengan una repercusión directa en el funcionamiento global de los centros clínicos en general. Junto a las labores tradicionales en el quirófano, los especialistas en Anestesiología y Reanimación también están muy presentes en las áreas médicas y quirúrgicas a través de la atención a los enfermos críticos, el tratamiento del dolor agudo y crónico, el cuidado del paciente durante los procedimientos diagnósticos y terapéuticos, y la atención de los enfermos más graves en las áreas de Urgencias. La declaración de Helsinki reconoce la importancia de la seguridad y la gestión de riesgos en los diferentes contextos de trabajo del anestesiólogo y suscribe los estándares de seguridad de la Federación Mundial de Sociedades de Anestesiología (2008). También reconoce la importancia creciente del propio paciente como sujeto de derechos y protagonista principal en el proceso de toma de decisiones que afecten a su salud. La declaración de Helsinki también confirma la trascendencia de la educación y la formación no sólo de los propios especialistas, sino también del resto de profesionales y proveedores sanitarios(AU)

Esta iniciativa coincide con otros programas auspiciados por otras instituciones en que también se enfatiza la importancia de la seguridad y la gestión de los riesgos en los diferentes contextos clínicos. Así, por ejemplo, la Organización Mundial de la Salud, en su estrategia mundial por la seguridad del paciente y con el lema de “la cirugía segura salva vidas”, formula el reto de sistematizar la cumplimentación de listados de seguridad o “checklists” en todas las intervenciones quirúrgicas (Schlack & Boersmester, 2010). Esta iniciativa se recoge en la declaración de Helsinki y también confluye con las recomendaciones de diferentes sociedades científicas. La mención expresa a la importancia de mantener registros y análisis de morbilidad, mortalidad e incidentes críticos reconoce igualmente la necesidad de aplicar metodologías de gestión de la calidad en el ámbito de la Anestesiología. Otra cuestión relevante es que los servicios de Anestesiología deben disponer de protocolos de trabajo y de guías de actuación ante las situaciones clínicas y cuestiones operativas que más riesgo pueden generar. En definitiva, la declaración de Helsinki constituye un valioso documento que se alinea perfectamente con las recomendaciones que, en materia de prácticas seguras, han sido emitidas por diferentes instituciones nacionales e internacionales. El alto grado de acuerdo entre los líderes de la Anestesiología Europea, dentro de la Unión Europea de Médicos Especialistas (UEMS), demuestra que la seguridad sigue constituyendo un objetivo prioritario en la actividad diaria de los anestesiólogos en todo el mundo. La declaración de Helsinki, junto a los documentos relacionados emanados desde las sociedades científicas europeas, contribuirá a que nuestra especialidad siga estando en la vanguardia de la calidad y la seguridad en la práctica clínica(AU)

Peripheral blood monocyte subsets predict antiviral response in chronic hepatitis C.

BACKGROUND: Hepatitis C virus infection evolves into chronic progressive liver disease in a significant percentage of patients. Monocytes constitute a diverse group of myeloid cells that mediate innate and adaptive immune response. In addition to proinflammatory CD16+ monocytes, a Tie-2+ subgroup - Tie-2 expressing monocytes (TEMs) - that has robust proangiogenic potential has been recently defined. AIM: To study the heterogeneity of peripheral blood monocytes in chronic hepatitis C (CHC) patients and to examine their proposed pathophysiological roles on disease progression and response to antiviral therapy. METHODS: We studied CD16+ and Tie-2+ peripheral monocyte subpopulations in 21 healthy subjects and 39 CHC patients in various stages of disease and responses to antiviral treatment using flow cytometry. Expression profiles of proangiogenic and tissue remodelling factors in monocyte supernatants were measured using ELISA and protein arrays. Intrahepatic expression of CD14, CD31 and Tie-2 was analysed using immunofluorescence. RESULTS: Increases of certain peripheral monocyte subsets were observed in the blood of CHC patients, wherein those cells with proinflammatory (CD16+) or proangiogenic (TEMs) potential expanded (P < 0.005, both). Notably, TEMs were significantly increased in nonresponders, particularly those with lower CD16 expression. In addition, many angiogenic factors were differentially expressed by peripheral monocytes from control or CHC patients, such as angiopoietin-1 and angiogenin (P < 0.05). Interestingly, intrahepatic TEMs were distinguished within portal infiltrates of CHC patients. CONCLUSIONS: These findings suggest for the first time the relevance of peripheral monocytes phenotypes for the achievement of response to treatment. Hence, the study of monocyte subset regulation might effect improved CHC prognoses and adjuvant therapies.

Estudio de utilización de analgésicos opiáceos en un hospital general universitario / Study of opioid analgesic use in a general university hospital

Objetivo: El objetivo de este trabajo ha sido realizar un estudio de utilización de analgésicos opiáceos en el Hospital Universitario La Paz (Madrid) en el año 2008 para conocer cómo se está utilizando este grupo de medicamentos y cuál es la tendencia del consumo. Para ello, se presentan los datos de uso de opiáceos en pacientes ingresados de forma global, por hospitales y por servicios clínicos. Se exponen los datos de consumo de los 5 últimos años y se ha cuantificado el uso del resto de principios activos empleados como analgésicos en nuestro hospital. Material y métodos: Haciendo uso de la metodología recomendada por la Organización Mundial de la Salud para los estudios de utilización de medicamentos en hospitales, presentamos nuestros datos en dosis diarias definidas (DDD) por 100 estancias. Los datos de consumo se han obtenido del programa de gestión de medicamentos del Servicio de Farmacia Farma Tools (Dominion®) Resultados: El valor global de utilización de opiáceos en 2008 ha sido de 8,1 DDD/100estancias. Los principios activos más consumidos han sido la morfina parenteral y el fentanilo transdérmico, y entre los 2 representan el 83% del consumo total de opiáceos. En el análisis por hospitales apreciamos que el Hospital General y el de Traumatología son los que presentan un mayor empleo de opiáceos y siguen el mismo patrón de utilización que el global. Los servicios más representativos del consumo de opiáceos han sido las reanimaciones del Hospital General y de Traumatología, los Servicios de Oncología, Cuidados paliativos y Hematología. En estos últimos 5 años se ha producido un incremento global del consumo de aproximadamente el 20%, viéndose implicados todos los principios activos. Con relación al consumo total de analgésicos, los datos reflejan una amplia utilización en el hospital (104 DDD/100 estancias)...(AU)

Objective: The aim of this study was to analyze opioid analgesic use in the La Paz University Hospital in 2008 in order to identify patterns of use and consumption. To that end, data from inpatients were analyzed overall, as well as by hospitals and departments. We analyzed data on consumption in the previous 5 years and quantified the use of there maining active principles administered as analgesics in our hospital. Materials and methods: Following the Wold Health Organization’s guidelines for studies on medication use in hospitals, data are shown as defined daily dose (DDD) per 100hospital stays. Data on drug use were obtained from the drug management program, Farma Tools (Dominion®), which is used by the Pharmacy Service at La Paz Hospital. Results: The overall value of opioid utilization in 2008 was 8.1 DDD per 100 hospital stays. The most widely used active principles were parenteral morphine and transdermal fentanyl. Together, these drugs represented 83% of total opioid consumption. Analysis by hospital revealed that the General and Traumatology Hospitals showed the highest opioiddrug consumption and followed the same utilization pattern as overall use. The services most representative of opioid consumption in inpatients were the Recovery Room in the General and Traumatology Hospitals, Critical Care, Oncology, Hematology and Palliative Care. In the last 5 years of the study, the overall use of these drugs increased by 20%, irrespective of the active principles involved. Analysis of analgesic intake at La Paz Hospital showed widespread use (104 DDD per 100 hospital stays). Opioids represented7.4% of total analgesic consumption, the most frequently used analgesics being acetaminophen and metamizol. Conclusions: The results of our study show an increasing trend in opioid consumption in this hospital...(AU)