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The delay in controlling the disease in patients who do not respond to first-line treatment with first generation somatostatin receptor ligands (first-generation SRLs) can be quantified in years, as every modification in the medical therapy requires some months to be fully evaluated. Considering this, acromegaly treatment should benefit from personalized medicine therapeutic approach by using biomarkers identifying drug response. Pasireotide has been positioned mostly as a compound to be used in first-generation SRLs resistant patients and after surgical failure, but sufficient data are now available to indicate it is a first line therapy for patients with certain characteristics. Pasireotide has been proved to be useful in patients in which hyperintensity T2 MRI signal is shown and in those depicting low SST2 and high expression of SST5, low or mutated AIP condition and sparsely granulated immunohistochemical pattern. This combination of clinical and pathological characteristics is unique for certain patients and seems to cluster in the same cases, strongly suggesting an etiopathogenic link. Thus, in this paper we propose to include this clinico-pathologic phenotype in the therapeutic algorithm, which would allow us to use as first line medical treatment those compounds with the highest potential for achieving the fastest control of GH hypersecretion as well as a positive effect upon tumor shrinkage, therefore accelerating the implementation of precision medicine for acromegaly. Moreover, we suggest the development, validation and clinical use of a pasireotide acute test, able to identify patients responsive to pasireotide LAR as the acute octreotide test is able to do for SRLs.

Alu repeats constitute a major fraction of human genome and for a small subset of them a role in gene regulation has been described. The number of studies focused on the functional characterization of particular Alu elements is very limited. Most Alu elements are DNA methylated and then assumed to lie in repressed chromatin domains. We hypothesize that Alu elements with low or variable DNA methylation are candidates for a functional role. In a genome-wide study in normal and cancer tissues, we pinpointed an Alu repeat (AluSq2) with differential methylation located upstream of the promoter region of the DIEXF gene. DIEXF encodes a highly conserved factor essential for the development of zebrafish digestive tract. To characterize the contribution of the Alu element to the regulation of DIEXF we analysed the epigenetic landscapes of the gene promoter and flanking regions in different cell types and cancers. Alternate epigenetic profiles (DNA methylation and histone modifications) of the AluSq2 element were associated with DIEXF transcript diversity as well as protein levels, while the epigenetic profile of the CpG island associated with the DIEXF promoter remained unchanged. These results suggest that AluSq2 might directly contribute to the regulation of DIEXF transcription and protein expression. Moreover, AluSq2 was DNA hypomethylated in different cancer types, pointing out its putative contribution to DIEXF alteration in cancer and its potential as tumoural biomarker.

Introduction: Epidural analgesia is an effective technique for postoperative pain relief. Our aim in this retrospective study was to assess the postoperative pain control and complications relating to epidural technique in laparoscopic radical prostatectomy (LRP). Material and methods: A retrospective analysis of 193 patients who underwent LRP, in which epidural analgesia was the postoperative pain approach, was performed. The procedure is generally performed under combined anesthesia. Data collected was postoperative pain data; appearance of neurological disorders (Bromage scale was used for motor weakness assessment); data related to the epidural technique and possible difficulties when performing it; data on epidural infusion; catheter-related complications; hospital stay, postoperative complications, and outcome. Results: Firstly, average VAS at rest was 1.2 ± 1.6; and upon movement, average VAS was 1.9 ± 1.8 during the hospital stay. Secondly, complications related to epidural technique appeared in 37 % of patients. There were 3 cases of hematic puncture; 3 accidental catheter disconnections; 1 dural puncture, and 1 subdural block. As for neurological secondary effects of local anesthetics in the epidural technique, 56 patients (30.1 %) presented with motor block of one or both lower extremities after surgery, and 5 (2.7 %) with paresthesia. Statistical analysis showed that motor weakness was not related to age, weight, type of local anesthetic used, infusion rate, level of epidural puncture nor length of catheter within the epidural space (p > 0.05). Conclusion: Postoperative epidural analgesia offers excellent analgesic quality but it can be associated with several complications secondary to the use of local anesthetics, which could disagree with the terms of Fast-track surgery. New techniques like the TAP block could offer the same analgesic quality, without the epidural´s technique potential complications. RESUMEN Objetivos: La analgesia epidural es una técnica eficaz para el control del dolor postoperatorio. Nuestro objetivo en este estudio retrospectivo fue evaluar el control del dolor postoperatorio mediante la escala visual analógica del dolor (EVA) y las complicaciones relacionadas con la técnica epidural, en la prostatectomía radical laparoscópica (PRL). Material y métodos: Llevamos a cabo un análisis retrospectivo de 193 pacientes sometidos a PRL, en los que se realizó la técnica epidural analgésica para el control del dolor postoperatorio. El procedimiento se hizo bajo una anestesia combinada. Registramos los datos relacionados con el dolor postoperatorio; la aparición de sintomatología neurológica (la escala de Bromage se utilizó para evaluar la debilidad motora); datos relacionados con la técnica epidural y posibles dificultades al realizarla; datos sobre la infusión epidural, como tipo de anestésico local utilizado; complicaciones relacionadas con el catéter y complicaciones postoperatorias asociadas al mismo, estancia hospitalaria y resultado. Resultados: En primer lugar, durante la estancia hospitalaria de los pacientes, el EVA promedio en reposo fue 1,2 ± 1,6; y durante el movimiento, el EVA promedio fue de 1,9 ± 1,8. En segundo lugar, las complicaciones relacionadas con la técnica epidural aparecieron en el 37 % de los pacientes. Hubo 3 casos de punción hemática; 3 desconexiones accidentales del catéter, 1 punción dural y 1 bloqueo subdural. En cuanto a las complicaciones neurológicas debidas a los efectos secundarios de los anestésicos locales en la técnica epidural, 56 (30,1 %) pacientes presentaron bloqueo motor de una o ambas extremidades inferiores después de la cirugía y 5 (2,7 %) refirieron parestesias. No hubo ninguna complicación neurológica que persistiese tras el alta hospitalaria. El análisis estadístico mostró que la debilidad motora no estaba relacionada con la edad, el peso, el tipo de anestésico local utilizado, la velocidad de infusión, el nivel de punción epidural ni la longitud del catéter en el espacio epidural (p > 0,05). Conclusión: La analgesia epidural postoperatoria ofrece una excelente calidad analgésica, pero puede estar asociada a varias complicaciones secundarias al uso de anestésicos locales, lo que podría estar en contraposición con las tendencias actuales de cirugía fastrack. Las nuevas técnicas emergentes podrían ofrecer la misma calidad analgésica evitando las potenciales complicaciones de la técnica epidural.

The aim was to determine in what areas the therapeutic application of soy predominates in clinical trials and to assess the emerging fields of its use by means of an analysis of bibliographic resources. A search was performed in the MEDLINE database up to 31 december 2004, limited to the Title/Abstract field, and Clinical Trials as the type of publication. The abstracts from the publications selected (n=86) were reviewed and different variables were assessed. A total of 3280 subjects were included: 15% men and 59% women (71% postmenopausal). The studies were performed basically in healthy individuals (71%). Twenty five percent of the studies investigated plasma levels of different metabolites and 21% determined hormone or lipid profiles. After the year 2000 a new population focus was detected, with the publication of two studies in elite gymnasts and judoists, with positive results. The present observations indicate that soy supplementation in the competitive sports elite may be an emerging application. El objetivo del estudio fue determinar cuales son las áreas de aplicación terapéutica de la soja que predominan en los ensayos clínicos y valorar los campos emergentes de su uso mediante un análisis bibliográfico. Para ello se realizó una busqueda en la base de datos de MEDLINE hasta el 31 de diciembre de 2004 limitando la busqueda en los campos Título/Resumen y Ensayo clínico como tipo de publicación. Se obtuvieron todos los resumenes de las publicaciones seleccionadas (n=86) eliminando los duplicados y se valoraron estadísticamente algunas variables reseñadas en ellos. Se incluyeron un total de 3280 sujetos: 15% de hombres y 59% de mujeres de las cuales un 71% eran menopaúsicas. Un 71% de los individuos se consideraron como sanos. Un 25% de los estudios habian investigado los niveles de algunos metabolitos plasmáticos y en un 21% de ellos los perfiles de lípidos u hormonas. A partir de las publicaciones del año 2000 se detectó un nuevo campo de aplicación con la publicación de dos estudios en deportistas de élite, gimnastas y judocas con resultados positivos. Las observaciones indican que la suplementación de la dieta de los deportistas de competición con proteina de soja puede ser una aplicación emergente

The aim was to determine in what areas the therapeutic application of soy predominates in clinical trials and to assess the emerging fields of its use by means of an analysis of bibliographic resources. A search was performed in the MEDLINE database up to 31 december 2004, limited to the Title/Abstract field, and Clinical Trials as the type of publication. The abstracts from the publications selected (n=86) were reviewed and different variables were assessed. A total of 3280 subjects were included: 15% men and 59% women (71% postmenopausal). The studies were performed basically in healthy individuals (71%). Twenty five percent of the studies investigated plasma levels of different metabolites and 21% determined hormone or lipid profiles. After the year 2000 a new population focus was detected, with the publication of two studies in elite gymnasts and judoists, with positive results. The present observations indicate that soy supplementation in the competitive sports elite may be an emerging application.