[Antimicrobial stewardship program in an Intensive Care Unit: A retrospective observational analysis of the results 15 months after its implementation]. / Programa de optimización del uso de antimicrobianos en un Servicio de Medicina Intensiva: análisis retrospectivo observacional de los resultados 15 meses después de su implementación.

OBJECTIVE: We aim to evaluate the adherence rate to an Antimicrobial Stewardship Program (ASP) in an Intensive Care Unit (ICU), and to assess its effect on the use of antibiotics, quality indicators and clinical outcomes. METHODS: Retrospective description of the interventions proposed by the ASP. We compared antimicrobial use, quality and safety indicators in an ASP versus a non-ASP period. The study was performed in a polyvalent ICU of a medium-size University Hospital (600 beds). We studied patients admitted to the ICU for any cause during the ASP period, provided that a microbiological sample aiming to diagnose a potential infection has been drawn, or antibiotics have been started. We elaborated and registered of non-mandatory recommendations to improve antimicrobial prescription (audit and feedback structure) and its registry during the ASP period (15 months, October 2018-December 2019). We compared indicators in a period with ASP (April-June 2019) and without ASP (April-June 2018). RESULTS: We issued 241 recommendations on 117 patients, 67% of them classified as de-escalation type. The rate of adherence to the recommendations was high (96.3%). In the ASP period, the mean number of antibiotics per patient (3.3±4.1 vs 2.4±1.7, p=0.04) and the days of treatment (155 DOT/100 PD vs 94 DOT/100 PD, p <0.01) were reduced. The implementation of the ASP did not compromise patient safety or produce changes in clinical outcomes. CONCLUSIONS: The implementation of an ASP is widely accepted in the ICU, reducing the consumption of antimicrobials, without compromising patient safety.

Percepción de utilidad entre profesionales sanitarios de un servicio de consultoría ética clínica / Healthcare workers’ perception of the usefulness of a healthcare ethics consultation service

Antecedentes y objetivo Los servicios de consultoría en ética clínica (CEC) surgen de los comités de ética para la asistencia sanitaria (CEAS) para atender conflictos éticos en tiempo real. Nuestro objetivo es conocer la percepción de utilidad de la CEC entre los profesionales sanitarios tras un año de su creación, así como evaluar los cambios de tendencia en el uso de la CEC y de los CEAS entre 2015 y 2021. Material y método Estudio observacional transversal mediante una encuesta estandarizada a los profesionales sanitarios de un hospital terciario urbano. Se compararon estos resultados con los de una encuesta idéntica realizada sobre la misma población en 2015. Resultados Participaron 213 profesionales (edad media 44 ± 11 años, 69% mujeres). Los profesionales conocían más la existencia de los CEAS que la CEC (94 vs. 61%; p<0,001). Un total de 45 encuestados (21%) habían consultado a la CEC desde su puesta en marcha; el 95% de ellos reconocían la utilidad de la consulta. Los facultativos conocían y utilizaban más la CEC que otros grupos profesionales. El grado de conocimiento sobre los CEAS en 2021 aumentó significativamente respecto a 2015 (94 vs. 76%; p<0,001). Se identificaron como áreas de mejora la necesidad de una mayor difusión del servicio, garantizar recursos institucionales para su mantenimiento y fomentar mayor participación de distintos profesionales. Conclusiones En los últimos años ha aumentado el conocimiento de los CEAS y de la CEC entre los profesionales sanitarios quienes consideran a la CEC útil para la atención de problemas éticos cotidianos (AU)

Background and objective Clinical ethics consultation services (CEC) have arisen from healthcare ethics committees (HEC) to address ethical conflicts in real-time. Our aim was to determine the perception of usefulness of a CEC service among healthcare workers one year after its creation as well as to assess changes in trends in the use of the CEC and HEC between 2015 and 2021. Material and method This observational, cross-sectional study was based on a standardized survey of healthcare workers at an urban tertiary care hospital. The results were also compared to those from an identical survey conducted in the same population in 2015. Results A total of 213 professionals participated (mean age 44±11 years, 69% women). The professionals were more familiar with the HEC than the CEC service (94 vs. 61%; p<0.001). Forty-five individuals (21%) had consulted the CEC since its implementation; 95% of them found the consultation useful. Physicians knew about and used the CEC more than other groups of professionals. The degree of knowledge of the HEC increased significantly by 2021 compared to 2015 (94 vs. 76%; p<0.001). Some areas for improvement identified were the need for greater dissemination of the service, guaranteeing institutional resources to maintain the service, and encouraging greater participation from different professional groups. Conclusions Knowledge of the institutional HEC and CEC services has increased in recent years among healthcare workers, who considered the CEC service to be useful for addressing ethical conflicts in daily practice (AU)

Healthcare workers' perception of the usefulness of a healthcare ethics consultation service.

BACKGROUND AND OBJECTIVE: Clinical ethics consultation services (CEC) have arisen from Healthcare Ethics Committees (HEC) to address ethical conflicts in real-time. Our aim was to determine the perception of usefulness of a CEC service among healthcare workers one year after its creation as well as to assess changes in trends in the use of the CEC and HEC between 2015 and 2021. MATERIALS AND METHODS: This observational, cross-sectional study was based on a standardized survey of healthcare workers at an urban tertiary care hospital. The results were also compared to those from an identical survey conducted in the same population in 2015. RESULTS: A total of 213 professionals participated (mean age 44 ± 11 years, 69% women). The professionals were more familiar with the HEC than the CEC service (94% vs 61%; p < 0.001). Forty-five individuals (21%) had consulted the CEC since its implementation; 95% of them found the consultation useful. Physicians knew about and used the CEC more than other groups of professionals. The degree of knowledge of the HEC increased significantly by 2021 compared to 2015 (94% v. 76%; p < 0.001). Some areas for improvement identified were the need for greater dissemination of the service, guaranteeing institutional resources to maintain the service, and encouraging greater participation from different professional groups. CONCLUSIONS: Knowledge of the institutional HEC and CEC services has increased in recent years among healthcare workers, who considered the CEC service to be useful for addressing ethical conflicts in daily practice.

Reflux patterns and risk factors of primary varicose veins' clinical severity.

OBJECTIVES: Primarily, to determine the association between the clinical severity of primary varicose veins and different reflux patterns in an anatomic and haemodynamic clinical study using duplex ultrasonography (DU). Secondly, to analyse the association of clinical severity with other aspects, such as risk factors for chronic venous insufficiency (CVI) and other concurrent diseases. METHOD: A total of 2036 limbs were evaluated using DU. Clinical status was characterized by the CEAP (clinical, aetiological, anatomical and pathological elements) classification. The degree of clinical severity was grouped into two categories, mild to moderate CVI (C1­C3)and severe CVI, characterized by the presence of skin changes (C4­C6). We analysed the association of the different reflux patterns with CEAP status. RESULTS: Saphenofemoral junction (SFJ) reflux of the great saphenous vein (GSV) was associated with the most severe form of the disease (odds ratio [OR] » 2.96; confidence interval [CI] 95%: 2.2­3.8), whereas competent SFJ of the GSV with reflux from proximal veins (OR » 2; CI 95%: 1.4­2.7) and the pure non-saphenous reflux (OR » 4.1; CI 95%:1.8­9.0) were associated with mild to moderate CVI. Obesity increased the frequency of severe CVI 2.7 times (OR » 2.7; CI 95%: 1.6­4.6); being a woman also increased the frequency of more severe disease 1.3 times (OR » 1.3; CI 95%: 1.0­1.7). CONCLUSION: Anatomical and haemodynamic studies by DU are postulated as a useful diagnostic tool that allow, by identifying the pattern of venous reflux of varicose pathology, characterization of the probable association to CVI clinical severity.

Tratamiento endovascular de los aneurismas poplíteos / No disponible

No disponible

Breast cancer stem cell hypothesis: clinical relevance (answering breast cancer clinical features)

The cancer stem cells hypothesis arises from observation of normal tissue hierarchy and the demonstration of stem cells in normal tissues. Scientists continue to debate whether the putative cancer cells derive from the transformation of normal tissue stem cells or from more differentiated cells. The existence of a subpopulation of tumour cells with stem-cell-like characteristics, including very slow replication and resistance to standard chemotherapy, posses a novel therapeutic challenge. This review summarises the state of development of normal and cancer breast cells and the clinical and therapeutic relevance (AU)

Increased interstitial pressure improves nucleic acid delivery to skin enabling a comparative analysis of constitutive promoters.

Nucleic acid-based therapies hold great promise for treatment of skin disorders if delivery challenges can be overcome. To investigate one mechanism of nucleic acid delivery to keratinocytes, a fixed mass of expression plasmid was intradermally injected into mouse footpads in different volumes, and reporter expression was monitored by intravital imaging or skin sectioning. Reporter gene expression increased with higher delivery volumes, suggesting that pressure drives nucleic acid uptake into cells after intradermal injections similar to previously published studies for muscle and liver. For spatiotemporal analysis of reporter gene expression, a dual-axis confocal (DAC) fluorescence microscope was used for intravital imaging following intradermal injections. Individual keratinocytes expressing hMGFP were readily visualized in vivo and initially appeared to preferentially express in the stratum granulosum and subsequently migrate to the stratum corneum over time. Fluorescence microscopy of frozen skin sections confirmed the patterns observed by intravital imaging. Intravital imaging with the DAC microscope is a noninvasive method for probing spatiotemporal control of gene expression and should facilitate development and testing of new nucleic acid delivery technologies.

Reflux or not reflux? Reflexiones sobre la publicación anglosajona del término en las varices primarias de los miembros inferiores en relación con nuestro entorno / Reflux or not reflux? Reflections on the term used in English language publications in relation to primary varicose veins of the lower limbs compared to that in Spanish literature

El significado práctico del término "reflux" en el estudio hemodinámico de las varices primarias publicado en la literatura varía en función del marco conceptual que se tenga de las distintas alteraciones hemodinámicas del sistema venoso. En este trabajo se exponen los fundamentos hemodinámicos y las discrepancias más interesantes entre la literatura anglosajona y "nuestro entorno"(AU)

The meaning of "reflux" in the haemodynamic study of primary varicose veins varies in the literature, according to different concepts of haemodynamic disorders of venous system. In this paper we present the haemodynamic basis and the main differences between English and Spanish literature(AU)

siRNA silencing of keratinocyte-specific GFP expression in a transgenic mouse skin model.

Small interfering RNAs (siRNAs) can be designed to specifically and potently target and silence a mutant allele, with little or no effect on the corresponding wild-type allele expression, presenting an opportunity for therapeutic intervention. Although several siRNAs have entered clinical trials, the development of siRNA therapeutics as a new drug class will require the development of improved delivery technologies. In this study, a reporter mouse model (transgenic click beetle luciferase/humanized monster green fluorescent protein) was developed to enable the study of siRNA delivery to skin; in this transgenic mouse, green fluorescent protein reporter gene expression is confined to the epidermis. Intradermal injection of siRNAs targeting the reporter gene resulted in marked reduction of green fluorescent protein expression in the localized treatment areas as measured by histology, real-time quantitative polymerase chain reaction and intravital imaging using a dual-axes confocal fluorescence microscope. These results indicate that this transgenic mouse skin model, coupled with in vivo imaging, will be useful for development of efficient and 'patient-friendly' siRNA delivery techniques and should facilitate the translation of siRNA-based therapeutics to the clinic for treatment of skin disorders.

Probiotics and autoimmunity: an evolutionary perspective.

Probiotics are microorganisms that have demonstrated beneficial effects on human health. Probiotics are usually isolated from the commensal microflora that inhabits the skin and mucosas. We propose that probiotics represent the species of microorganisms that have established a symbiotic relationship with humans for the longest time. Cultural practices of ancient human societies used to favor that symbiosis and the transmission of probiotics from generation to generation. New practices, introduced as a result of industrialization, such as childbirth by surgical delivery, ingestion of pasteurized and synthetic compounds-supplemented food, cleaner homes, indiscriminate use of antibiotics and so on, have led in recent years to the replacement of probiotics by other microorganisms that are not as well adapted to the microenvironments of the human body. These newly settled microorganisms lack many of the beneficial effects of probiotics. Our hypothesis is that the sudden change (from an evolutive perspective) in human intestinal microflora may importantly contribute to the rise in the incidence of autoimmune diseases, observed in the last half a century.

Impact of Transcription Units rearrangement on the evolution of the regulatory network of gamma-proteobacteria

In the past years, several studies begun to unravel the structure, dynamical properties, and evolution of transcriptional regulatory networks. However, even those comparative studies that focus on a group of closely related organisms are limited by the rather scarce knowledge on regulatory interactions outside a few model organisms, such as E. coli among the prokaryotes. Results: In this paper we used the information annotated in Tractor_DB (a database of regulatory networks in gamma-proteobacteria) to calculate a normalized Site Orthology Score (SOS) that quantifies the conservation of a regulatory link across thirty genomes of this subclass. Then we used this SOS to assess how regulatory connections have evolved in this group, and how the variation of basic regulatory connection is reflected on the structure of the chromosome. We found that individual regulatory interactions shift between different organisms, a process that may be described as rewiring the network. At this evolutionary scale (the gamma-proteobacteria subclass) this rewiring process may be an important source of variation of regulatory incoming interactions for individual networks. We also noticed that the regulatory links that form feed forward motifs are conserved in a better correlated manner than triads of random regulatory interactions or pairs of co-regulated genes. Furthermore, the rewiring process that takes place at the most basic level of the regulatory network may be linked to rearrangements of genetic material within bacterial chromosomes, which change the structure of Transcription Units and therefore the regulatory connections between Transcription Factors and structural genes. Conclusion: The rearrangements that occur in bacterial chromosomes-mostly inversion or horizontal gene transfer events are important sources of variation of gene regulation at this evolutionary scale(AU)

En los últimos años, varios estudios han comenzado a desentrañar la estructura, la dinámica de las propiedades, y la evolución de las redes de regulación transcripcional. Sin embargo, incluso los estudios comparativos que se centran en un grupo de organismos estrechamente relacionados son limitados por la escasez de conocimientos en lugar de reglamentación sobre las interacciones fuera de unos pocos organismos modelo, como la E. coli entre los procariotas. Resultados En este trabajo se utilizó la información anotada en Tractor_DB (una base de datos de redes reguladoras en gamma proteobacteria) para calcular un sitio normalizado Orthology Puntuación (SOS) que cuantifica la conservación de un vínculo de reglamentación a través de treinta genomas de esta subclase. A continuación, hemos utilizado este SOS para evaluar cómo han evolucionado las conexiones de reglamentación en este grupo, y cómo la variación de la relación básica de regulación se refleja en la estructura del cromosoma. Se encontró que cada cambio de reglamentación interacciones entre los diferentes organismos, proceso que puede describirse como el cableado de la red. En esta escala evolutiva (la gamma-proteobacteria subclase) este proceso de cableado pueden ser una importante fuente de variación de la reglamentación de las interacciones individuales redes. Hemos observado también que la reglamentación que forman enlaces de alimentación hacia adelante motivos se conservan en una mejor correlación de las tríadas de manera aleatoria o reglamentario interacciones de pares de genes co-regulados. Además, el proceso de cableado que se lleva a cabo en el nivel más básico de regulación de la red pueden estar relacionados con reordenamientos del material genético de bacterias dentro de los cromosomas, que cambiar la estructura de las unidades de transcripción y, por tanto, el marco regulador conexiones entre factores de transcripción y genes estructurales......

Aneurisma de carótida extracraneal con estenosis crítica contralateral / Extracranial carotid aneurysm with contralateral critical stenosis

Introducción. Los aneurismas de carótida extracraneal son una patología poco frecuente y de etiología variable, aunque con una gran relevancia clínica. Sus manifestaciones son principalmente neurológicas y de origen tromboembólico. El tratamiento de elección es quirúrgico en la mayoría de casos, mediante la resección y revascularización. Caso clínico. Presentamos el caso de un paciente con un aneurisma de bulbo carotídeo, y una estenosis crítica contralateral tratado en nuestro servicio. El diagnóstico se realizó mediante ecografía Doppler asociada a una tomografía axial computarizada y una angiografía. El tratamiento consistió en una endarterectomía carotídea contralateral, seguida ocho semanas después de la resección del aneurisma y la reconstrucción mediante un injerto de Dacron impregnado en rifampicina, y el reimplante de la carótida externa. La evolución posterior ha sido favorable, sin complicaciones neurológicas. Discusión. Los aneurismas de carótida extracraneal son raros, pero tienen una gran relevancia clínica debido al alto porcentaje de complicaciones neurológicas que presentan. Además, debe tenerse en cuenta su posible etiología infecciosa. El tratamiento conservador sólo se justifica en una minoría de los casos, ya que el resto requiere únicamente un tratamiento quirúrgico. Los resultados de la reconstrucción justifican esta actitud; la ligadura carotídea se reserva en escasas indicaciones. Existen pocas publicaciones sobre la terapéutica endoluminal aplicada a esta patología, por lo que aún no puede considerarse una clara alternativa (AU)

One gene determines maize B chromosome accumulation by preferential fertilisation; another gene(s) determines their meiotic loss.

Genotypes of high (H(m)) and low (L(m)) male B transmission rate (B-TR) were obtained. B-TR segregation in the F2 is reported, showing that the H(m) and L(m) lines differ in a single locus we call mBt (male B transmission), controlling B preferential fertilisation in maize. The egg cells control which one of the sperm nuclei is going to fertilise them, mBt(h) egg cells being preferentially fertilised by the sperm nucleus carrying the supernumerary B chromosomes (Bs). It is hypothesised that the mBt gene is involved in the normal fertilisation of maize but the parasitic Bs take advantage of the mBt(h) allele to increase their own transmission. Selection was also carried out when the Bs were transmitted on the female side (H(f) and L(f) lines). The F1 hybrids show that the gene(s) that we call fBt (female B transmission), controlling female B-TR, is located on the A chromosomes acting at diploid level, the fBt(l) allele(s) for low transmission being dominant. This allele causes the loss of Bs at meiosis, which is shown using a specific B molecular probe to determine B presence/absence in microspores of both lines and hybrids. Maize Bs are a nice example of intragenome conflict, because the mBt and fBt loci are a polymorphic system of attack and defence between A and B chromosomes.

[Screening for colorectal cancer predisposition]. / Detección de la predisposición al cáncer colorrectal.

In the last years the advantages in molecular biology have developed a variety of useful tests in order to detect genetic mutations. These mutations are associated to a susceptibility of suffering a colo-rectal cancer. The genetic tests are designed to screen the disease although many problems can emerge when they are offered to the population. In this article, we will try to analyze the advantages, disadvantages and the present indications for genetic testing in colo-rectal cancer, particularity in cases of familial adenomatous polyposis and nonpolyposis inherited colon cancer.