[Impact of the Covid-19 pandemic on specialized healthcare training in a teaching center]. / Impacto de la pandemia COVID-19 en la formación sanitaria especializada en un centro docente.

OBJECTIVE: Evaluation of the impact of the health crisis caused by the Covid-19 pandemic on specialized healthcare training in a teaching center. METHODS: Cross-sectional descriptive study, by means of an electronic questionnaire sent to 167 residents in June 2020, to evaluate the burden of care, suspension of rotations and Covid-19 symptoms. The impact on the acquisition of professional competencies was measured using a four-level Likert scale (none, a little, quiet, a lot). The profile of acquired competencies was constructed and its association with the professional profile was studied using Generalized Linear Models. The qualitative approach was carried out through an open question on how it influenced their learning and the different categories were extracted through triangulation. RESULTS: The impact on learning was important for 94.8% of the residents. A total of 81.4% left the rotations they were doing and reported high workload, loss of training opportunities, uncertainty and ethical conflicts. They appreciated significant learning in the competencies of teamwork (93.2%), professionalism (86.2%), ethics (79.9%) and communication (78%). Technical competencies were deficient. The final balance of learning was perceived as positive by 54.4%, especially residents in central services and medical specialties. A total of 67.8% felt overwhelmed at times due to fatigue-emotional impact, care overload, ethical conflicts and lack of resources. CONCLUSIONS: The Covid-19 pandemic had an exceptional impact on specialized health care training. It is necessary to re-evaluate training programs to ensure the acquisition of the technical competencies that are lacking.

Una estrategia para la formación en seguridad del paciente durante la residencia: desde el incidente crítico a la simulación. Parte 2 / A strategy for training in patient safety during residency programme: From critical incident to simulation. Part 2

La formación en seguridad del paciente durante la residencia contribuye a la cultura de la seguridad y a la calidad asistencial. Un currículum para formar en seguridad incorpora distintas actividades formativas a lo largo de la especialidad y adecuadas a cada momento: cursos, talleres, sesiones de incidente crítico, rondas de seguridad, que se han descrito anteriormente, y simulación. La simulación permite el entrenamiento seguro de situaciones clínicas complejas en equipos multiprofesionales. Estructurar el aprendizaje de factor humano mediante el manejo de recursos en las crisis, y proporcionar feedback en el debriefing mejora la competencia. La simulación puede formar parte de la evaluación formativa objetiva de los residentes. Se ha demostrado que tiene resultados en el desempeño de los profesionales sanitarios, mejora la calidad de la asistencia y tiene efectos sobre los pacientes

Patient safety training during residency contributes to the culture of safety and quality of care. Patient safety curriculum incorporates different activities throughout the specialty and appropriate to each moment: courses, workshops, critical incident sessions, safety rounds, which have been described above, and simulation. The simulation allows the safe training of complex clinical situations in multiprofessional teams. Structure the learning of human factor through the management of resources in crises, and provide feedback in debriefing improves competition. The simulation can be part of the objective formative evaluation of the residents. It has been shown to have results in the performance of health professionals, improves the quality of care and has effects on patients

Una estrategia para la formación en seguridad del paciente durante la residencia: desde el incidente crítico hasta la simulación. Parte 1 / A strategy for training in patient safety during residency programme: From critical incident to simulation. Part 1

La formación en seguridad del paciente durante la residencia contribuye a la cultura de la seguridad y a la calidad asistencial. Un currículum para formar en seguridad incorpora distintas actividades formativas a realizar a lo largo de la especialidad y adecuadas a cada momento formativo. Desde la incorporación del residente, los cursos de seguridad, comunicación, ética, los talleres de lavado de manos, de técnicas, junto con los recursos de Internet, lo van dotando de diferentes competencias. Adquiere la competencia en seguridad con la integración en la actividad asistencial diaria de la valoración de los riesgos, la detección y la comunicación de incidentes, y el análisis de eventos adversos. Acelera el aprendizaje reflexionando de forma estructurada y aprendiendo del error con los incidentes críticos y la simulación

Patient safety training during residency contributes to the culture of safety and quality of care. Patient safety curriculum incorporates different activities to be carried out throughout the residence and appropriate to each training moment. Since the incorporation of the resident the courses of security, communication, ethics, hand washing workshops, techniques, together with Internet resources are endowing him with knowledge and skills. Acquires security competence with the integration of risk assessment, detection and communication of incidents and the analysis of adverse events into the daily assistance activity. Accelerates learning by reflecting in a structured way and learning from error with critical incidents and simulation

Tuning porosity in macroscopic monolithic metal-organic frameworks for exceptional natural gas storage.

Widespread access to greener energy is required in order to mitigate the effects of climate change. A significant barrier to cleaner natural gas usage lies in the safety/efficiency limitations of storage technology. Despite highly porous metal-organic frameworks (MOFs) demonstrating record-breaking gas-storage capacities, their conventionally powdered morphology renders them non-viable. Traditional powder shaping utilising high pressure or chemical binders collapses porosity or creates low-density structures with reduced volumetric adsorption capacity. Here, we report the engineering of one of the most stable MOFs, Zr-UiO-66, without applying pressure or binders. The process yields centimetre-sized monoliths, displaying high microporosity and bulk density. We report the inclusion of variable, narrow mesopore volumes to the monoliths' macrostructure and use this to optimise the pore-size distribution for gas uptake. The optimised mixed meso/microporous monoliths demonstrate Type II adsorption isotherms to achieve benchmark volumetric working capacities for methane and carbon dioxide. This represents a critical advance in the design of air-stable, conformed MOFs for commercial gas storage.

Análisis de la actividad de interconsulta realizada por los servicios de medicina interna. Estudio REINA-SEMI: Registro de Interconsultas y Asistencia Compartida de la Sociedad Española de Medicina Interna / Analysis of the activity of interconsultations conducted by the departments of internal medicine. REINA-SEMI study: Registry of Interconsultations and Shared Care of the Spanish Society of Internal Medicine

Objetivo: Analizar la actividad de interconsulta (IC) realizada por los servicios de medicina interna (MI), sus aspectos formales, el perfil de la atención clínica requerida y cuantificar la carga de trabajo que supone. Material y método: Estudio multicéntrico, observacional, prospectivo, sobre enfermos consecutivos hospitalizados atendidos por servicios de MI mediante IC entre el 15 de mayo y el 15 de junio del año 2016. Se estimó la carga de trabajo relacionada con dicha actividad (1UT=10min). Resultados: Se registraron 1.141 IC procedentes de 43 hospitales, edad 69,4 (DE: 16,2) años, 51,2% hombres. El índice de Charlson fue 2,3 (DE: 2,2). Los motivos de consulta más frecuentes fueron: valoración general (27,4%), fiebre (18,1%), disnea (13,6%), trastorno metabólico (9,6%), HTA (6,3%) y síndrome confusional (5,3%). Las UT estimadas fueron 4 (DE: 5,9) para la primera visita y 7,3 (DE: 21,5) para la suma de las sucesivas. Los pacientes quirúrgicos fueron mayores (70,6 [DE: 15,9] vs 64,4 [DE: 16,3]; p=0,0001) y precisaron más días de seguimiento (5 [DE: 7,3] vs 3,5 [DE: 4,2]; p=0,009). Los siguientes aspectos fueron más frecuentes en el formato de las IC realizadas por servicios médicos: número de IC ordinarias (respuesta >24h), especificación del motivo de IC, datos mínimos referentes a la historia clínica y coincidencia de la adecuación en el tiempo con el consultor. Conclusión: Los pacientes atendidos mediante IC por los servicios de MI representan una carga de trabajo importante. La adecuación al formato de solicitud de IC es mayor en las procedentes de servicios médicos

Objective: To analyse the activity of interconsultations conducted by internal medicine (IM) departments, their formal aspects and the profile of clinical care required and to quantify the workload they represent. Material and method: A multicentre, observational prospective study was conducted with consecutive hospitalised patients treated by IM departments using interconsultations between May 15 and June 15, 2016. We estimated the workload related to this activity (1time unit [TU]=10min). Results: We recorded 1,141 interconsultations from 43 hospitals. The mean age of the patients involved was 69.4 years (SD: 16.2), and 51.2% were men. The mean Charlson index was 2.3 (SD: 2.2). The most common reasons for the consultations were general assessments (27.4%), fever (18.1%), dyspnoea (13.6%), metabolic disorder (9.6%), arterial hypertension (6.3%) and delirium (5.3%). The duration of the first visit was 4 TUs (SD: 5.9) and 7.3 (SD: 21.5) for the sum of all subsequent visits. The surgical patients were older (70.6 [SD, 15.9] vs. 64.4 [SD, 16.3] years; P=.0001) and required more follow-up time (5 [SD, 7.3] vs. 3.5 [SD, 4.2] days; P=.009). The following issues were more common in the interconsultation format performed by medical services: number of regular interconsultations (response >24h), specification of the reason for the interconsultation, minimal data regarding the medical history and agreement on the appropriateness of the time spent with the consultant. Conclusion: The patients treated through interconsultations by the IM departments represented a significant workload. The interconsultations from the medical departments were more in line with the request format

Mechanical reliability of dental grade zirconia after laser patterning.

The aim of this work is to test the mechanical properties of dental zirconia surfaces patterned with Nd:YAG laser interference (λ = 532 nm and 10 ns pulse). The laser treatment produces an alteration of the topography, engraving a periodic striped pattern. Laser-material interaction results mainly in thermal effects producing microcracking, phase transformation and texturization. The role of such microstructural modifications and collateral damage on the integrity and mechanical performances has been assessed. Laser patterned discs of zirconia doped with 3% mol yttria (3Y-TZP) have been tested before and after a thermal treatment to anneal residual stresses and revert phase transformation. Both groups of samples behave in a similar manner, excluding residual stresses and phase transformation from the origin of properties modification. Result show that laser patterning induces a minor decrease in mechanical properties and surface integrity of 3Y-TZP surfaces. The biaxial strength decreases as a consequence of the damage induced by laser patterning. Fractographic observations identify preexisting defects enlarged by local laser interaction as the fracture origins. The Hardness and Young modulus of treated surfaces tested with nanoindentation also decrease slightly after laser treatment and this may be attributed to laser-induced microcracking.

Analysis of the activity of interconsultations conducted by the departments of internal medicine. REINA-SEMI study: Registry of Interconsultations and Shared Care of the Spanish Society of Internal Medicine. / Análisis de la actividad de interconsulta realizada por los servicios de medicina interna. Estudio REINA-SEMI: Registro de Interconsultas y Asistencia Compartida de la Sociedad Española de Medicina Interna.

OBJECTIVE: To analyse the activity of interconsultations conducted by internal medicine (IM) departments, their formal aspects and the profile of clinical care required and to quantify the workload they represent. MATERIAL AND METHOD: A multicentre, observational prospective study was conducted with consecutive hospitalised patients treated by IM departments using interconsultations between May 15 and June 15, 2016. We estimated the workload related to this activity (1time unit [TU]=10min). RESULTS: We recorded 1,141 interconsultations from 43 hospitals. The mean age of the patients involved was 69.4 years (SD: 16.2), and 51.2% were men. The mean Charlson index was 2.3 (SD: 2.2). The most common reasons for the consultations were general assessments (27.4%), fever (18.1%), dyspnoea (13.6%), metabolic disorder (9.6%), arterial hypertension (6.3%) and delirium (5.3%). The duration of the first visit was 4 TUs (SD: 5.9) and 7.3 (SD: 21.5) for the sum of all subsequent visits. The surgical patients were older (70.6 [SD, 15.9] vs. 64.4 [SD, 16.3] years; P=.0001) and required more follow-up time (5 [SD, 7.3] vs. 3.5 [SD, 4.2] days; P=.009). The following issues were more common in the interconsultation format performed by medical services: number of regular interconsultations (response >24h), specification of the reason for the interconsultation, minimal data regarding the medical history and agreement on the appropriateness of the time spent with the consultant. CONCLUSION: The patients treated through interconsultations by the IM departments represented a significant workload. The interconsultations from the medical departments were more in line with the request format.

Identification and Characterization of a Secondary Sodium-Binding Site and the Main Selectivity Determinants in the Human Concentrative Nucleoside Transporter 3.

The family of concentrative Na+/nucleoside cotransporters in humans is constituted by three subtypes, namely, hCNT1, hCNT2, and hCNT3. Besides their different nucleoside selectivity, hCNT1 and hCNT2 have a Na+/nucleoside stoichiometry of 1:1, while for hCNT3 it is 2:1. This distinct stoichiometry of subtype 3 might hint the existence of a secondary sodium-binding site that is not present in the other two subtypes, but to date their three-dimensional structures remain unknown and the residues implicated in Na+ binding are unclear. In this work, we have identified and characterized the Na+ binding sites of hCNT3 by combining molecular modeling and mutagenesis studies. A model of the transporter was obtained by homology modeling, and key residues of two sodium-binding sites were identified and verified with a mutagenesis strategy. The structural model explains the altered sodium-binding properties of the hCNT3C602R polymorphic variant and supports previously generated data identifying the determinant residues of nucleoside selectivity, paving the way to understand how drugs can target this plasma membrane transporter.

Intercambiabilidad de resultados entre los diferentes laboratorios clínicos Catlab / Comparability study of analytical results between a group of clinical laboratories

Objetivo. Describir el estudio de la intercambiabilidad de los resultados de las magnitudes de bioquímica que se procesan indistintamente en los 4 laboratorios de Catlab. Material y métodos. Se establecieron requisitos de calidad de coeficiente de variación y error total (CV% y ET%). Se verificó, con materiales de control comercial, el cumplimiento del CV% en cada magnitud y para cada analizador de cada laboratorio y se estudió la intercambiabilidad con muestras recientes de suero. Se analizaron las diferencias con una aplicación en Microsoft Access® que genera gráficos de Bland-Altman modificados. Resultados. La intercomparación de las 32 magnitudes que se realizan en más de un laboratorio o analizador generó 306 gráficas de Bland-Altman: 101 (33,1%) cumplían directamente el requisito de ET% establecido a partir de la variabilidad biológica y 205 (66,9%) requirieron revisión. Se reprocesaron los datos según los requisitos mínimos de consenso de la Asociación Española de Farmacéuticos Analistas (AEFA), la Sociedad Española de Bioquímica Clínica y Enfermedad Molecular (SEQC), la Asociación Española de Biopatología Médica (AEBM) y de la Sociedad Española de Hematología y Hemoterapia (SEHH) de octubre del 2013. Aplicándolos, 170 comparaciones (56%) cumplían directamente los requisitos y 136 (44%) requerían revisión. Al valorar el número de puntos que excedían el requisito, los errores aleatorios, el intervalo de resultados en el que se detectaban discrepancias y el intervalo de decisión clínica se consideró que todos los resultados se podían aceptar y que las 32 magnitudes eran intercambiables en todos los centros y analizadores. Conclusiones. A partir del requisito de consenso de las 4 sociedades, los resultados de todas las magnitudes comparadas eran intercambiables. No obstante, cada uno de los laboratorios debe cumplir con criterios más estrictos de error total (AU)

Objective. To describe the study of the comparability of the measurements levels of biological tests processed in biochemistry in Catlab's 4 laboratories. Material and methods. Quality requirements, coefficients of variation and total error (CV% and TE %) were established. Controls were verified with the precision requirements (CV%) in each test and each individual laboratory analyser. Fresh serum samples were used for the comparability study. The differences were analysed using a Microsoft Access® application that produces modified Bland-Altman plots. Results. The comparison of 32 biological parameters that are performed in more than one laboratory and/or analyser generated 306 Bland-Altman graphs. Of these, 101 (33.1%) fell within the accepted range of values based on biological variability, and 205 (66.9%) required revision. Data were re-analysed based on consensus minimum specifications for analytical quality (consensus of the Asociación Española de Farmacéuticos Analistas (AEFA), the Sociedad Española de Bioquímica Clínica y Patología Molecular (SEQC), the Asociación Española de Biopatología Médica (AEBM) and the Sociedad Española de Hematología y Hemoterapia (SEHH), October 2013). With the new specifications, 170 comparisons (56%) fitted the requirements and 136 (44%) required additional review. Taking into account the number of points that exceeded the requirement, random errors, range of results in which discrepancies were detected, and range of clinical decision, it was shown that the 44% that required review were acceptable, and the 32 tests were comparable in all laboratories and analysers. Conclusions. The analysis of the results showed that the consensus requirements of the 4 scientific societies were met. However, each laboratory should aim to meet stricter criteria for total error (AU)

Role of SLC22A1 polymorphic variants in drug disposition, therapeutic responses, and drug-drug interactions.

The SCL22A1 gene encodes the broad selectivity transporter hOCT1. hOCT1 is expressed in most epithelial barriers thereby contributing to drug pharmacokinetics. It is also expressed in different drug target cells, including immune system cells and others. Thus, this membrane protein might also contribute to drug pharmacodynamics. Up to 1000 hOCT1 polymorphisms have been identified so far, although only a small fraction of those have been mechanistically studied. A paradigm in the field of drug transporter pharmacogenetics is the impact of hOCT1 gene variability on metformin clinical parameters, affecting area under the concentration-time curve, Cmax and responsiveness. However, hOCT1 also mediates the translocation of a variety of drugs used as anticancer, antiviral, anti-inflammatory, antiemetic agents as well as drugs used in the treatment of neurological diseases among. This review focuses exclusively on those drugs for which some pharmacogenetic data are available, and aims at highlighting the need for further clinical research in this area.

[Comparability study of analytical results between a group of clinical laboratories]. / Intercambiabilidad de resultados entre los diferentes laboratorios clínicos Catlab.

OBJECTIVE: To describe the study of the comparability of the measurements levels of biological tests processed in biochemistry in Catlab's 4 laboratories. MATERIAL AND METHODS: Quality requirements, coefficients of variation and total error (CV% and TE %) were established. Controls were verified with the precision requirements (CV%) in each test and each individual laboratory analyser. Fresh serum samples were used for the comparability study. The differences were analysed using a Microsoft Access® application that produces modified Bland-Altman plots. RESULTS: The comparison of 32 biological parameters that are performed in more than one laboratory and/or analyser generated 306 Bland-Altman graphs. Of these, 101 (33.1%) fell within the accepted range of values based on biological variability, and 205 (66.9%) required revision. Data were re-analysed based on consensus minimum specifications for analytical quality (consensus of the Asociación Española de Farmacéuticos Analistas (AEFA), the Sociedad Española de Bioquímica Clínica y Patología Molecular (SEQC), the Asociación Española de Biopatología Médica (AEBM) and the Sociedad Española de Hematología y Hemoterapia (SEHH), October 2013). With the new specifications, 170 comparisons (56%) fitted the requirements and 136 (44%) required additional review. Taking into account the number of points that exceeded the requirement, random errors, range of results in which discrepancies were detected, and range of clinical decision, it was shown that the 44% that required review were acceptable, and the 32 tests were comparable in all laboratories and analysers. CONCLUSIONS: The analysis of the results showed that the consensus requirements of the 4 scientific societies were met. However, each laboratory should aim to meet stricter criteria for total error.

Contact fatigue of veneer feldspathic porcelain on dental zirconia.

OBJECTIVES: To understand the resistance to cyclic and static contact loading of feldspathic porcelain on dental zirconia (3Y-TZP), in order to understand the partial failure of porcelain (chipping or cracking). METHODS: Hertzian contact techniques were used to evaluate the appearance of damage as a ring crack in terms of applied load and number of cycles in air and simulated saliva. RESULTS: Static contact loading showed the presence of stress corrosion cracking in the porcelain; the environmental crack growth in air was determined from the results of time to damage under static load. There was also a contribution of fatigue effects due to the interactions of the crack with the microstructure. From the obtained results, a time to failure was estimated depending on the material counterpart. Cracking can occur on porcelain coatings if the contact counterpart is teeth or porcelain in a time interval of a few years, consistent with clinical studies. SIGNIFICANCE: Contact loading, particularly against teeth or other ceramic materials can be a significant cause of failure and chipping of feldspathic porcelain on zirconia, especially if the patient suffers from bruxism. Protection, by e.g. a guard, against repetitive contact against the porcelain can increase the lifetime of the veneer.

Human organic cation transporter 1 (hOCT1) as a mediator of bendamustine uptake and cytotoxicity in chronic lymphocytic leukemia (CLL) cells.

Bendamustine is used in the treatment of chronic lymphocytic leukemia (CLL). Routes for bendamustine entry into target cells are unknown. This study aimed at identifying transporter proteins implicated in bendamustine uptake. Our results showed that hOCT1 is a bendamustine transporter, as bendamustine could cis-inhibit the uptake of a canonical hOCT1 substrate, with a Ki in the micromolar range, consistent with the EC50 values of the cytotoxicity triggered by this drug in HEK293 cells expressing hOCT1. hOCT1 polymorphic variants determining impaired bendamustine-transporter interaction, consistently reduced bendamustine cytotoxicity in HEK293 cells stably expressing them. Exome genotyping of the SLC22A1 gene, encoding hOCT1, was undertaken in a cohort of 241 CLL patients. Ex vivo cytotoxicity to bendamustine was measured in a subset of cases and shown to correlate with SLC22A1 polymorphic variants. In conclusion, hOCT1 is a suitable bendamustine transporter, thereby contributing to its cytotoxic effect depending upon the hOCT1 genetic variants expressed.

Nucleoside transporters and human organic cation transporter 1 determine the cellular handling of DNA-methyltransferase inhibitors.

BACKGROUND AND PURPOSE: Inhibitors of DNA methyltransferases (DNMTs), such as azacytidine, decitabine and zebularine, are used for the epigenetic treatment of cancer. Their action may depend upon their translocation across the plasma membrane. The aim of this study was to identify transporter proteins contributing to DNMT inhibitor action. EXPERIMENTAL APPROACH: Drug interactions with selected hCNT and hENT proteins were studied in transiently transfected HeLa and MDCK cells. Interaction with human organic cation transporters (hOCTs) was assessed in transiently transfected HeLa cells and Xenopus laevis oocytes. KEY RESULTS: Zebularine uptake was mediated by hCNT1, hCNT3 and hENT2. Decitabine interacted with but was not translocated by any nucleoside transporter (NT) type. hCNT expression at the apical domain of MDCK cells promoted net vectorial flux of zebularine. Neither hOCT1 nor hOCT2 transported decitabine, but both were involved in the efflux of zebularine, suggesting these proteins act as efflux transporters. hOCT1 polymorphic variants, known to alter function, decreased zebularine efflux. CONCLUSIONS AND IMPLICATIONS: This study highlights the influence of human NTs and hOCTs on the pharmacokinetics and pharmacodynamics of selected DNMT inhibitors. As hOCTs may also behave as efflux transporters, they could contribute either to chemoresistance or to chemosensitivity, depending upon the nature of the drug or combination of drugs being used in cancer therapy.

Concentrative nucleoside transporter 1 (hCNT1) promotes phenotypic changes relevant to tumor biology in a translocation-independent manner.

Nucleoside transporters (NTs) mediate the uptake of nucleosides and nucleobases across the plasma membrane, mostly for salvage purposes. The canonical NTs belong to two gene families, SLC29 and SLC28. The former encode equilibrative nucleoside transporter proteins (ENTs), which mediate the facilitative diffusion of natural nucleosides with broad selectivity, whereas the latter encode concentrative nucleoside transporters (CNTs), which are sodium-coupled and show high affinity for substrates with variable selectivity. These proteins are expressed in most cell types, exhibiting apparent functional redundancy. This might indicate that CNTs have specific roles in the physiology of the cell beyond nucleoside salvage. Here, we addressed this possibility using adenoviral vectors to restore tumor cell expression of hCNT1 or a polymorphic variant (hCNT1S546P) lacking nucleoside translocation ability. We found that hCNT1 restoration in pancreatic cancer cells significantly altered cell-cycle progression and phosphorylation status of key signal-transducing kinases, promoted poly-(ADP-ribose) polymerase hyperactivation and cell death and reduced cell migration. Importantly, the translocation-defective transporter triggered these same effects on cell physiology. Moreover, this study also shows that restoration of hCNT1 expression is able to reduce tumor growth in a mouse model of pancreatic adenocarcinoma. These data predict a novel role for a NT protein, hCNT1, which appears to be independent of its role as mediator of nucleoside uptake by cells. Thereby, hCNT1 fits the profile of a transceptor in a substrate translocation-independent manner and is likely to be relevant to tumor biology.

Comparación de 3 combinaciones de levobupivacaína al 0,5 por ciento y de mepivacaína al 1 por ciento en el bloqueo del nervio ciático poplíteo, en la cirugía ambulatoria del hallux valgus / Comparison of 3 combinations of 0.5 percent levobupivacaine and 1percent mepivacaine in popliteal sciatic block in hallux valgus outpatient surgery

Objetivo: Comparar 3 combinaciones de levobupivacaína 0,5% con mepivacaína 1% en bloqueo del ciático poplíteo con dosis única para cirugía del hallux valgus. Métodos: Estudio prospectivo, doble ciego, en pacientes programados para cirugía ambulatoria de hallux valgus con bloqueo del nervio ciático poplíteo guíado por ultrasonidos. Los pacientes se distribuyeron aleatoriamente en 3 grupos, según el volumen de cada uno de los anestésicos locales: G1, levobupivacaína 20 mL + mepivacaína 10 mL, G2, levobupivacaína 10 mL + mepivacaína 20 mL y G3, levobupivacaína 15 mL + mepivacaína 15 mL. Fueron evauados el tiempo de inicio, de reversión y el tiempo total del bloqueo de los nervios tibial y peroneo; control del dolor postoperatorio a las 12, 24, 72 h y al séptimo día del postoperatorio mediante escala visual analógica (EVA), escala descriptiva simple (EDS) y la calidad del descanso nocturno; complicaciones postoperatorias y satisfacción del paciente. Resultados: Se incluyó a 120 pacientes, 40 por grupo. Los grupos fueron homogéneos y ningún paciente precisó anestesia complementaria. El tiempo de latencia del bloqueo fue significativamente mayor en el G1 respecto a G2 y G3 (39,4 ± 14,7 min frente a 32,2 ± 16,5 y 33,2 ± 12 min). El tiempo de reversión del bloqueo sensitivo y motor fue significativamente mayor en G1 respecto a G2 y G3 (29,5 ± 9,3 h frente a 22,2 ± 8,2 y 24,8 ± 7,9 h). El nivel máximo de dolor se registró a las 24 h del postoperatorio y fue significativamente superior en el G2 respecto al G1. El descanso nocturno también fue peor la primera noche en el G2 respecto al G1. La satisfacción del paciente fue buena o muy buena y no se registraron complicaciones. Conclusiones: El tiempo de latencia del bloqueo y la eficacia anestésica fueron adecuados en los 3 grupos. La combinación de levobupivacaína 0,5% 20 ml y mepivacaína 1% 10 ml es una buena alternativa para una analgesia postoperatoria más duradera(AU)

Background: To compare 3 combinations of 0.5% levobupivacaine (L) and 1% mepivacaine (M) for popliteal block for hallux valgus surgery. Methods: Prospective, double blind study of 120 patients undergoing unilateral hallux valgus outpatient surgery with posterior popliteal block with ultrasound-guided single injection. Patients were randomly allocated into three groups: G1: 20 mL L + 10 mL M; G2: 10 mL L + 20 mL M; and G3: 15 mL L + 15 mL M. Recorded variables were: time of block, onset and reversal times for tibial and peroneal nerves block; postoperative pain until the 7th day by means of visual analogue scale (VAS), simple descriptive scale and the quality of nocturnal rest, complications, and patient satisfaction. ANOVA and chi2 were applied in the statistical analysis, with a P < 0.05 considered significant. Results: Groups were homogeneous for demographic and surgical characteristics. None of the patients required intraoperative complementary analgesia or anaesthesia. Block onset was significantly longer in G1 than in G2 and G3 (39.4 ± 14.7 versus 32.2 ± 16.5 and 33.2 ± 12 minutes). Recovery time from sensory and motor block was significantly longer in G1 than in G2 and G3 (29.5 ± 9.3 versus 22.2 ± 8.2 and 24.8 ± 7.9 hours). Postoperative pain level was below VAS 30 (1-100) in the three groups; none of the patients experienced severe pain. Maximum pain level appeared at 24 h postoperatively. Patient satisfaction was high and there were no complications. Conclusions: Block onset time and anaesthetic efficacy was adequate in the three groups. The combination of 20 mL levobupivacaine 0.5% with 10 mL mepivacaine 1% provide a good alternative for a lasting postoperative analgesia(AU)

[Comparison of 3 combinations of 0.5% levobupivacaine and 1% mepivacaine in popliteal sciatic block in hallux valgus outpatient surgery]. / Comparación de 3 combinaciones de levobupivacaína al 0,5% y de mepivacaína al 1% en el bloqueo del nervio ciático poplíteo, en la cirugía ambulatoria del hallux valgus.

BACKGROUND: To compare 3 combinations of 0.5% levobupivacaine (L) and 1% mepivacaine (M) for popliteal block for hallux valgus surgery. METHODS: Prospective, double blind study of 120 patients undergoing unilateral hallux valgus outpatient surgery with posterior popliteal block with ultrasound-guided single injection. Patients were randomly allocated into three groups: G1: 20mL L+10mL M; G2: 10mL L+20mL M; and G3: 15mL L+15mL M. Recorded variables were: time of block, onset and reversal times for tibial and peroneal nerves block; postoperative pain until the 7(th) day by means of visual analogue scale (VAS), simple descriptive scale and the quality of nocturnal rest, complications, and patient satisfaction. ANOVA and chi2 were applied in the statistical analysis, with a P<0.05 considered significant. RESULTS: Groups were homogeneous for demographic and surgical characteristics. None of the patients required intraoperative complementary analgesia or anaesthesia. Block onset was significantly longer in G1 than in G2 and G3 (39.4±14.7 versus 32.2±16.5 and 33.2±12minutes). Recovery time from sensory and motor block was significantly longer in G1 than in G2 and G3 (29.5±9.3 versus 22.2±8.2 and 24.8±7.9hours). Postoperative pain level was below VAS 30 (1-100) in the three groups; none of the patients experienced severe pain. Maximum pain level appeared at 24h postoperatively. Patient satisfaction was high and there were no complications. CONCLUSIONS: Block onset time and anaesthetic efficacy was adequate in the three groups. The combination of 20mL levobupivacaine 0.5% with 10mL mepivacaine 1% provide a good alternative for a lasting postoperative analgesia.

Up-regulation of FXR isoforms is not required for stimulation of the expression of genes involved in the lack of response of colon cancer to chemotherapy.

Several mechanisms are involved in the poor response of colorectal adenocarcinoma (CRAC) to pharmacological treatment. Since preliminary evidences have suggested that the enhanced expression of farnesoid X receptor (FXR) results in the stimulation of chemoresistance, we investigated whether FXR up-regulation is required for the expression of genes that characterize the multidrug resistance (MDR) phenotype of CRAC. Samples of tumours and adjacent healthy tissues were collected from naive patients. Using Taqman Low-Density Arrays, the abundance of mRNA of 87 genes involved in MDR was determined. Relevant changes were re-evaluated by conventional RT-QPCR. In healthy tissue the major FXR isoforms were FXRα2(+/-) (80%). In tumours this predominance persisted (91%) but was accompanied by a consistent reduction (3-fold) in total FXR mRNA. A lower FXR expression was confirmed by immunostaining, in spite of which there was a significant change in the expression of MDR genes. Pharmacological challenge was simulated "in vitro" using human CRAC cells (LS174T cells). Short-term (72h) treatment with cisplatin slightly increased the almost negligible expression of FXR in wild-type LS174T cells, whereas long-term (months) treatment induced a cisplatin-resistant phenotype (LS174T/R cells), which was accompanied by a 350-fold up-regulation of FXR, mainly FXRα1(+/-). However, the changed expression of MDR genes in LS174T/R cells was not markedly affected by incubation with the FXR antagonist Z-guggulsterone. In conclusion, although the enhanced expression of FXR may be involved in the stimulation of chemoresistance that occurs during pharmacological treatment, FXR up-regulation is not required for the presence of the MDR phenotype characteristic of CRAC.

No correlation between the expression of FXR and genes involved in multidrug resistance phenotype of primary liver tumors.

Farnesoid X receptor (FXR) has been recently reported to enhance chemoresistance through bile acid-independent mechanisms. Thus, FXR transfection plus activation with GW4064 resulted in reduced sensitivity to cisplatin-induced toxicity. This is interesting because primary tumors of the liver, an organ where FXR is expressed, exhibit marked refractoriness to pharmacological treatment. Here we have determined whether FXR is upregulated in hepatocellular carcinoma (HCC), cholangiocarcinoma (CGC) and hepatoblastoma (HPB) and whether this is related with the expression of genes involved in mechanisms of chemoresistance. Using RT-QPCR and Taqman low density arrays we have analyzed biopsies from healthy livers or surgically removed tumors from naive patients and cell lines derived from HCC (SK-HEP-1, Alexander and Huh7), CGC (TFK1) and HPB (HepG2), before and after exposure to cisplatin at IC50 for 72 h. In liver tumors FXR expression was not enhanced but significantly decreased (healthy liver > HCC > HPB ≈ CGC). Except for CGC, this was not accompanied by changes in the proportions of FXR isoforms. Changes in 36 genes involved in drug uptake/efflux and metabolism, expression/function of molecular targets, and survival/apoptosis balance were found. Changes affecting SLC22A1, CYP2A1 and BIRC5 were shared by HCC, CGC and HPB. Similarity in gene expression profiles between cell lines and parent tumors was found. Pharmacological challenge with cisplatin induced changes that increased this resemblance. This was not dependent upon FXR expression. Thus, although FXR may play a role in inducing chemoresistance under certain circumstances, its upregulation does not seem to be involved in the multidrug resistance phenotype characteristic of HCC, CGC and HPB.