Prevalence, risk factors and evolution of diabetes mellitus after treatment in primary aldosteronism. Results from the SPAIN-ALDO registry.

PURPOSE: To evaluate the prevalence, risk factors and evolution of diabetes mellitus (DM) after targeted treatment in patients with primary aldosteronism (PA). METHODS: A retrospective multicenter study of PA patients in follow-up at 27 Spanish tertiary hospitals (SPAIN-ALDO Register). RESULTS: Overall, 646 patients with PA were included. At diagnosis, 21.2% (n = 137) had DM and 67% of them had HbA1c levels < 7%. In multivariate analysis, family history of DM (OR 4.00 [1.68-9.53]), the coexistence of dyslipidemia (OR 3.57 [1.51-8.43]) and advanced age (OR 1.04 per year of increase [1.00-1.09]) were identified as independent predictive factors of DM. Diabetic patients were on beta blockers (46.7% (n = 64) vs. 27.5% (n = 140), P < 0.001) and diuretics (51.1% (n = 70) vs. 33.2% (n = 169), p < 0.001) more frequently than non-diabetics. After a median follow-up of 22 months [IQR 7.5-63.0], 6.9% of patients developed DM, with no difference between those undergoing adrenalectomy and those treated medically (HR 1.07 [0.49-2.36], p = 0.866). There was also no significant difference in the evolution of glycemic control between DM patients who underwent surgery and those medically treated (p > 0.05). CONCLUSION: DM affects about one quarter of patients with PA and the risk factors for its development are common to those of the general population. Medical and surgical treatment provides similar benefit in glycemic control in patients with PA and DM.

Detección de nefrotóxicos y ajuste de dosis en pacientes con filtrado glomerular bajo realizado en farmacia comunitaria: metodología / Detection of nephrotoxicants and dose adjustment in patients with low glomerular filtration rate performed in community pharmacy: methodology

La enfermedad renal crónica es un problema prevalente y sin tratamiento específico. La detección tem prana es importante, siendo el Filtrado Glomerular estimado (FGe) una prueba muy asequible que puede realizarse en farmacia comunitaria. Si se presenta, es muy importante no dañar más el riñón evitando el uso de medicamentos nefrotóxicos y ajustar las dosis de otros medicamentos de eliminación renal, y la farmacia comunitaria está muy bien posicionada para ello. Objetivo: describir la metodología utilizada para detectar nefrotóxicos y ajustar dosis de otros medica mentos en farmacia comunitaria para su posterior derivación a atención primaria. Método: estudio experimental de seguimiento no controlado multicéntrico realizado en farmacias comunitarias de 4 comunidades autónomas de España. Se incluyen pacientes que cumplen criterios de inclusión y firman el consentimiento informado. Se estudian aquellos con FGe<60 ml/min/1,73m2 y se analiza su medicación utilizando el BOT Plus y otras 4 fuentes de información. Resultado: se incluyen 670 pacientes, 215 de ellos con FGe<60ml/min/1,73m2. De ellos 90 (41,9 %) necesitaron algún tipo de ajuste a juicio del farmacéutico. De estos 90 el 43,3 % (39) tuvieron algún tipo de cambio posteriormente a la intervención del farmacéutico. Conclusión: en pacientes con filtrado glomerular bajo, con la metodología adecuada, el farmacéutico comunitario es capaz de detectar la utilización de medicamentos nefrotóxicos o la utilización de medicamentos a dosis superiores a las recomendadas en función de su estado renal. Detección de nefrotóxicos y ajuste de dosis en pacientes con filtrado glomerular bajo realizado en farmacia comunitaria: metodología (AU)

Chronic kidney disease is a prevalent problem without specific treatment. Early detection is important and estimated glomerular filtration rate (eGFR) is a very affordable test that can be performed in community pharmacies. If present, it is very important not to further damage the kidney by avoiding the use of neph rotoxic drugs and adjusting the doses of other renal elimination drugs and the community pharmacy is very well positioned to do this. Objective: To describe the methodology used to detect nephrotoxic drugs and adjust doses of other drugs in community pharmacies for subsequent referral to primary care. Method: Multicentre experimental multicentre uncontrolled follow-up study carried out in communi ty pharmacies in 4 autonomous communities in Spain. Patients who met the inclusion criteria and signed the informed consent form were included. Those with eGFR <60 ml/min/1.73m2 were studied and their medication was analysed using the BOT Plus and 4 other sources of information. Result: 670 patients were included, 215 of them with eGFR<60ml/min/1.73m2. Of these 90 (41.9%) needed some type of adjustment in the pharmacist’s judgement. Of these 90, 43.3% (39) had some kind of change after the pharmacist’s intervention C onclusion: In patients with low glomerular filtration rate, with the appropriate methodology, the community pharmacist is able to detect the use of nephrotoxic drugs or the use of drugs at doses higher than those recommended according to their renal status (AU)

Functional analysis of mTERF5 and mTERF9 contribution to salt tolerance, plastid gene expression and retrograde signalling in Arabidopsis thaliana.

We previously showed that Arabidopsis mda1 and mterf9 mutants, defective in the chloroplast-targeted mitochondrial transcription termination factors mTERF5 and mTERF9, respectively, display altered responses to abiotic stresses and abscisic acid (ABA), as well as perturbed development, likely through abnormal chloroplast biogenesis. To advance the functional analysis of mTERF5 and mTERF9, we obtained and characterized overexpression (OE) lines. Additionally, we studied genetic interactions between sca3-2, affected in the plastid-RNA polymerase RpoTp, and the mda1-1 and mterf9 mutations. We also investigated the role of mTERF5 and mTERF9 in plastid translation and plastid-to-nucleus signalling. We found that mTERF9 OE reduces salt and ABA tolerance, while mTERF5 or mTERF9 OE alter expression of nuclear and plastid genes. We determined that mda1-1 and mterf9 mutations genetically interact with sca3-2. Further, plastid 16S rRNA levels were reduced in mda1-1 and mterf9 mutants, and mterf9 was more sensitive to chemical inhibitors of chloroplast translation. Expression of the photosynthesis gene LHCB1, a retrograde signalling marker, was differentially affected in mda1-1 and/or mterf9 compared to wild-type Col-0, after treatments with inhibitors of carotenoid biosynthesis (norflurazon) or chloroplast translation (lincomycin). Moreover, mterf9, but not mda1-1, synergistically interacts with gun1-1, defective in GUN1, a central integrator of plastid retrograde signals. Our results show that mTERF9, and to a lesser extent mTERF5, are negative regulators of salt tolerance and that both genes are functionally related to RpoTp, and that mTERF9 is likely required for plastid ribosomal stability and/or assembly. Furthermore, our findings support a role for mTERF9 in retrograde signalling.

NOTCH1 mutations identify a genetic subgroup of chronic lymphocytic leukemia patients with high risk of transformation and poor outcome.

NOTCH1 has been found recurrently mutated in a subset of patients with chronic lymphocytic leukemia (CLL). To analyze biological features and clinical impact of NOTCH1 mutations in CLL, we sequenced this gene in 565 patients. NOTCH1 mutations, found in 63 patients (11%), were associated with unmutated IGHV, high expression of CD38 and ZAP-70, trisomy 12, advanced stage and elevated lactate dehydrogenase. Sequential analysis in 200 patients demonstrated acquisition of mutation in one case (0.5%) and disappearance after treatment in two. Binet A and B patients with NOTCH1-mutated had a shorter time to treatment. NOTCH1-mutated patients were more frequently refractory to therapy and showed shorter progression-free and overall survival after complete remission. Overall survival was shorter in NOTCH1-mutated patients, although not independently from IGHV. NOTCH1 mutation increased the risk of transformation to diffuse large B-cell lymphoma independently from IGHV, with this being validated in resampling tests of replicability. In summary, NOTCH1 mutational status, that was rarely acquired during the course of the disease, identify a genetic subgroup with high risk of transformation and poor outcome. This recently identified genetic subgroup of CLL patients deserves prospective studies to define their best management.

Next-generation sequencing reveas the secrets of the chronic lymphocytic leukemia genome

The study of the detailed molecular history of cancer development is one of the most promising techniques to understand and fight this diverse and prevalent disease. Unfortunately, this history is as diverse as cancer itself. Therefore, even with next-generation sequencing techniques, it is not easy to distinguish significant (driver) from random (passenger) events. The International Cancer Genome Consortium (ICGC) was formed to solve this fundamental issue by coordinating the sequencing of samples from 50 different cancer types and/or sub-types that are of clinical and societal importance. The contribution of Spain in this consortium has been focused on chronic lymphocytic leukemia (CLL). This approach has unveiled new and unexpected events in the development of CLL. In this review, we introduce the approaches utilized by the consortium for the study of the CLL genome and discuss the recent results and future perspectives of this work (AU)

Deubiquitinases in cancer: new functions and therapeutic options.

Deubiquitinases (DUBs) have fundamental roles in the ubiquitin system through their ability to specifically deconjugate ubiquitin from targeted proteins. The human genome encodes at least 98 DUBs, which can be grouped into 6 families, reflecting the need for specificity in their function. The activity of these enzymes affects the turnover rate, activation, recycling and localization of multiple proteins, which in turn is essential for cell homeostasis, protein stability and a wide range of signaling pathways. Consistent with this, altered DUB function has been related to several diseases, including cancer. Thus, multiple DUBs have been classified as oncogenes or tumor suppressors because of their regulatory functions on the activity of other proteins involved in tumor development. Therefore, recent studies have focused on pharmacological intervention on DUB activity as a rationale to search for novel anticancer drugs. This strategy may benefit from our current knowledge of the physiological regulatory mechanisms of these enzymes and the fact that growth of several tumors depends on the normal activity of certain DUBs. Further understanding of these processes may provide answers to multiple remaining questions on DUB functions and lead to the development of DUB-targeting strategies to expand the repertoire of molecular therapies against cancer.

[Treatment of a giant serpentine type middle cerebral artery aneurysm with a high-flow bypass from the petrous internal carotid artery]. / Tratamiento de un aneurisma serpentino gigante de arteria cerebral media conbypass de alto flujo desde la arteria carótida interna petrosa.

A case report of a giant serpentine type aneurysm arising from the M1 segment of the middle cerebral artery (MCA) treated with a high-flow external saphenous vein graft from the petrous segment of the internal carotid artery is presented. The steps and challenges of this demanding surgical technique are also described. The elements to be taken into consideration in the indication, design and realization of the bypass surgery in the treatment of the MCA aneurysms are discussed.

Tratamiento de un aneurisma serpentino gigante de arteria cerebral media con bypass de alto flujo desde la arteria carótida interna petrosa / Treatment of a giant serpentine type middle cerebral artery aneurysm with a high-flow bypass from the petrous internal carotid artery

Se presenta un caso de aneurisma gigante del segmento M1 de la arteria cerebral media (ACM), de tipo serpentino, tratado mediante bypass de alto flujo con vena safena externa desde la arteria carótida interna petrosa. Se describen los pasos de la cirugía y se destacan las dificultades de la técnica. Se discuten los elementos a considerar en la toma de decisiones para la indicación, diseño y realización del bypass en el tratamiento de los aneurismas de la ACM (AU)

A case report of a giant serpentine type aneurysm arising from the M1 segment of the middle cerebral artery (MCA) treated with a high-flow external saphenous vein graft from the petrous segment of the internal carotid artery is presented. The steps and challenges of this demanding surgical technique are also described. The elements to be taken into consideration in the indication, design and realization of the bypass surgery in the treatment of the MCA aneurysms are discused (AU)

[Management and microsurgical treatment of infundibular dilatations of the posterior communicating artery. Series of nine cases and review of the literature]. / Manejo y traramiento microquirurgico de las dilataciones infundibulares de la arteria comunicante posterior. Seri de nueve casos y revision de la literatura.

INTRODUCTION: The infundibular dilatation (ID) of the posterior communicating (PCom) artery is defined as the conic, triangular or infundibular shaped, less than 3mm wide, origin of the PCom artery from the internal carotid artery. The purpose of this paper is to present the personal experience in the microsurgical management of the ID, to review the literature and to propose some algorithms to improve its clinical and microsurgical management. MATERIAL AND METHODS: Nine cases of ID have been operated on through a pterional approach. In four patients with subarachnoid hemorrhage (SAH) the ID was considered as the potential source of the bleeding; in four cases the ID was treated after a SAH due to the rupture of an aneurysm; finally, an ID was treated in patient with diagnosis of pseudoxantoma elasticum. RESULTS: In eight cases the ID was clipped and the Pcom artery subsequently occluded and in the remaining case the ID was associated with a fetal PComA and the ID was reinforced. There were no complications excepting a transitory third cranial nerve paresis. The Glasgow Outcome Scale was 5 in all cases at discharge and one year later. CONCLUSIONS: The true significance of the ID remains unknown, but in some instances it is necessary to consider its management: 1. In patients with ruptured aneurysms submitted to microsurgical clipping and with an ipsilateral ID, the lesion must be explored and treated; 2. In patients with ruptured aneurysms treated with endovascular procedures or harbouring an ID contralateral to a microsurgically treated aneurysm, the microsurgical indication will be done after considering all risk factors; 3. In patients with SAH and an ID as the only potential source of the bleeding there would be an indication for microsurgical exploration; 4. The incidental finding of an ID should be indication for observation in absence of major risk factors.

Manejo y tratamiento microquirúrgico de las dilataciones infundibulares de la arteria comunicante posterior. Serie de nueve casos y revisión de la literatura / Management and microsurgical treatment of infun-dibular dilatations of the posterior communicating artery. Series of nine cases and review of the literature

Introducción. La dilatación infundibular (DI) de la arteria comunicante posterior (AComP) se define como la dilatación cónica, triangular o en forma de embudo, menor de 3 mm, en el origen de la AComP de la arte­ria carótida interna. El propósito del presente trabajo es presentar la experiencia propia en el tratamiento microquirúrgico de la DI de la AComP, revisar la biblio­grafía y proponer algoritmos para optimizar su manejo clínico y microquirúrgico. Material y métodos. Se han estudiado nueve casos de DI intervenidos a través de un abordaje pterional. En cuatro pacientes con hemorragia subaracnoidea (HSA) la DI se consideró la única causa del sangrado; en otros cuatro pacientes la DI se intervino tras una HSA por ruptura de otra lesión aneurismática; finalmente, en un paciente con pseudoxantoma elástico la DI se intervino de forma preventiva. Resultados. En ocho casos se procedió al clipaje de la DI y cierre de la AComP y en uno al reforzamiento de la DI al tratarse de una AComP del tipo fetal. No aparecie­ron complicaciones salvo una paresia transitoria del III par. El Glasgow Outcome Scale al alta y al año fue de 5 en todos los casos. Conclusiones. La DI de la AComP es una lesión de significado no aclarado, pero que plantea la necesidad de considerar su tratamiento en algunas ocasiones: 1. En pacientes con aneurismas rotos sometidos a cirugía y DI homolateral se recomienda explorar y tratar la lesión; (..) (AU)

Introduction. The infundibular dilatation (ID) of the posterior communicating (PCom) artery is defined as the conic, triangular or infundibular shaped, less than 3mm wide, origin of the PCom artery from the internal carotid artery. The purpose of this paper is to present the personal experience in the microsurgical manage­ment of the ID, to review the literature and to propose some algorithms to improve its clinical and microsurgi­cal management. Material and methods. Nine cases of ID have been operated on through a pterional approach. In four patients with subarachnoid hemorrhage (SAH) the ID was considered as the potential source of the bleeding; in four cases the ID was treated after a SAH due to the rupture of an aneurysm; finally, an ID was treated in patient with diagnosis of pseudoxantoma elasticum. Results. In eight cases the ID was clipped and the Pcom artery subsequently occluded and in the remai­ning case the ID was associated with a fetal PComA and the ID was reinforced. There were no complications excepting a transitory third cranial nerve paresis. The Glasgow Outcome Scale was 5 in all cases at discharge and one year later. Conclusions. The true significance of the ID remains unknown, but in some instances it is necessary to con­sider its management: 1. In patients with ruptured aneurysms submited to microsurgical clipping and with an ipsilateral ID, the lesion must be explored and treated; 2. In patients with ruptured aneurysms treated with endovascular procedures or harbouring an ID contralateral to a microsurgically treated aneurysm, the microsurgical indication will be done after conside­ring all risk factors; 3. In patients with SAH and an ID as the only potential source of the bleeding there would be an indication for microsurgical exploration; 4. The incidental finding of an ID should be indication for (..) (AU)

[Olfactory groove meningiomas. Radical microsurgical treatment through the bifrontal approach]. / Meningiomas del surco olfatorio. Tratamiento microquirúrgico radical por via bifrontal.

OBJECTIVES: To describe the microsurgical technique for the radical removal of olfactory groove meningiomas through the bifrontal approach. To review the diagnostic elements to be taken into account in the selection of the surgical approach to these tumours. MATERIALS AND METHODS: A microsurgical series of 35 olfactory groove meningiomas operated on through a bifrontal craniotomy is reviewed. RESULTS: The mean tumoral volume was 85cc (4.4cm diameter). A relevant peritumoral brain edema was found in 65.7% of cases, hyperostosis in the implantation base in 80% and paranasal sinus invasion in 28.6%. A Sipmson grade 1 resection was achieved in every case. A patient died due to a postoperative pneumonia. Postoperative hospitalization time was between 3 and 20 days and at discharge all patients had a Glasgow Outcome Scale grade 4-5. The mean follow-up was 55.2 months. Two patients had postoperative transient rhinolicuorrhea and an additional patient developed hydrocephalus. An asymptomatic recurrence have been identified in a patient four years after surgery. CONCLUSIONS: In our experience the bifrontal approach allowed the radical removal of huge olfactory groove meningiomas. The microdissection of the anterior cerebral artery A2 segments is possible thanks to the arachnoidal plane between vessels and tumor. Tumoral blood flow is secured by the early approaching of the base of the tumor and preoperative embolization is not necessary. Bifrontal approach allows an aggressive treatment of the hyperostosis, bone infiltration and paranasal sinus invasion. Anterior fossa reconstruction is done using a vascularized periosteal flap.

Meningiomas del surco olfatorio. Tratamiento microquirúrgico radical por vía bifrontal / Olfactory groove meningiomas. Radical microsurgical treatment through the bifrontal approach

Objetivos. Describir los detalles técnicos del abordajebifrontal para el tratamiento microquirúrgicoradical de los meningiomas del surco olfatorio. Revisarlos factores diagnósticos a valorar en la selección delabordaje quirúrgico de estos tumores.Material y métodos. Se revisa una serie microquirúrgicade 35 tumores del surco olfatorio intervenidospor vía bifrontal.Resultados. El volumen medio de las lesiones era de85 cc (4.4 cm de diámetro). El 65.7% presentaban edemacerebral perilesional relevante, el 80% hiperostosis enla base de implantación y el 28.6% invasión de los senosparanasales. En todos los casos se realizó una exéresisgrado 1 de Simpson. Hubo un éxitus por neumonía. Laestancia hospitalaria fue de 3-20 días, con un GlasgowOutcome Scale 4-5 al alta en todos los casos y seguimientomedio de 55.2 meses. Como complicacionesrelevantes destacan rinolicuorrea transitoria en doscasos e hidrocefalia en otro caso. Se ha identificado unarecidiva local asintomática en un paciente a los 4 años (..) (AU)

Objectives. To describe the microsurgical techniquefor the radical removal of olfactory groove meningiomasthrough the bifrontal approach. To review the diagnosticelements to be taken into account in the selection ofthe surgical approach to these tumours.Materials and methods. A microsurgical series of 35olfactory groove meningiomas operated on through abifrontal craniotomy is reviewed.Results. The mean tumoral volume was 85cc (4.4cmdiameter). A relevant peritumoral brain edema wasfound in 65.7% of cases, hyperostosis in the implantationbase in 80% and paranasal sinus invasion in28.6%. A Sipmson grade 1 resection was achievedin every case. A patient died due to a postoperativepneumonia. Postoperative hospitalization time wasbetween 3 and 20 days and at discharge all patientshad a Glasgow Outcome Scale grade 4-5. The meanfollow-up was 55.2 months. Two patients had postoperativetransient rhinolicuorrhea and an additional (..) (AU)

[Treatment of intrinsic brain tumors located in motor eloquent areas. Results of a protocol based in navigation, tractography and neurophysiological monitoring of cortical and subcortical structures]. / Tratamiento de los tumores cerebrales intrínsecos de áreas motoras elocuentes. Resultados de un protocolo basado en la navegación, tractografía y monitorización neurofisiológica de estructuras corticales y subcorticales.

OBJECTIVES: The role of the microsurgical management of intrinsic brain tumors is to maximize the volumetric resection of the tumoral tissue minimizing the postoperative morbidity. The purpose of our paper has been to study the benefits of an original protocol developed for the microsurgical treatment of tumors located in eloquent motor areas where the navigation and electrical stimulation of motor subcortical pathways have been implemented. MATERIALS AND METHODS: A total of 17 patients operated on for resection of cortical or subcortical tumors in motor areas were included in the series. Preoperative planning for multimodal navigation was done integrating anatomic studies, motor functional MRI (f-MRI) and subcortical pathways volumes generated by diffusion tensor imaging (DTI). Intraoperative neuromonitorization included motor mapping by direct cortical and subcortical electrical stimulation (CS and sCS) and localization of the central sulcus using cortical multipolar electrodes and the N20 wave inversion technique. The location of all cortical and subcortical stimulated points with positive motor response was stored in the navigator and correlated with the cortical or subcortical motor functional structures defined preoperatively. RESULTS: The mean tumoral volumetric resection was 89.1±14.2% of the preoperative volume, with a total resection (≥100%) in twelve patients. Preoperatively a total of 58.8% of the patients had some motor deficit, increasing 24 hours after surgery to 76.5% and decreasing to 41.1% a month later. There was a great correlation between anatomic and functional data, both cortically and subcortically. However, in six cases it was not possible to identify the central sulcus and in many cases fMRI gave contradictory information. A total of 52 cortical points submitted to CS had positive motor response, with a positive correlation of 83.7%. Also, a total of 55 subcortical points had positive motor response, being in these cases 7.3±3.1 mm the mean distance from the stimulated point to the subcortical tract. CONCLUSIONS: The integration of preoperative and intraoperative anatomic and functional studies allows a safe functional resection of the brain tumors located in eloquent areas, compared to the tumoral resection based on anatomic imaging studies. Multimodal navigation allows the integration and correlation among preoperative and intraoperative anatomic and functional data. Cortical motor functional areas are anatomically and functionally located preoperatively thanks to MRI and fMRI and subcortical motor pathways with TDI and tractography. Intraoperative confirmation is done with CS and N20 inversion wave for cortical structures and with sCS for subcortical pathways. With this protocol we achieved a mean of 90% of volumetric resection in cortical and subcortical tumors located in eloquent motor areas with an increase of neurological deficits in the immediate postoperative period that significantly decreased one month later. Ongoing studies will define the safe limits for functional resection taking into account the intraoperative brain shift. Finally, it must be demonstrated if this protocol has any benefit for patients concerning disease free or overall survival.

Tratamiento de los tumores cerebrales intrínsecos de áreas motoras elocuentes. Resultados de un protocolo basado en la navegación, tractografía y monitorizaciónneurofisiológica de estructuras corticales y subcorticales / Treatment of intrinsic brain tumors located in motor eloquent areas. results of a protocol based in navegation, tractography and neurophysiological monitoring of cortical and subcortical structures

Objetivos. El papel actual del tratamiento microquirúrgicode los tumores cerebrales intrínsecos se basaen alcanzar la máxima resección volumétrica del tumorminimizando la morbilidad postoperatoria. El propósitodel trabajo es estudiar los beneficios de un protocolodiseñado para tratar tumores localizados en áreaselocuentes motoras, en el que se incluye la navegación yla estimulación de tractos motores subcorticales.Material y métodos. Se han incluido 17 pacientescon tumores corticales y subcorticales de área motoratratados quirúrgicamente. Para la planificación preoperatoriase fusionaron en el sistema de navegaciónestudios anatómicos, de resonancia funcional motora(RNM-f) y los tractos subcorticales generados porestudios de tensor de difusión (DTI). La monitorizaciónintraoperatoria incluía el mapeo motor por estimulacióncortical y subcortical directa (ECD y EsCD) e identificacióndel surco central por inversión de la onda N20con electrodos corticales multipolares. La localizaciónde los puntos con respuesta positiva a la ECD o EsCD secorrelacionaba con las áreas corticales o tractos funcionalesmotores definidos en los estudios preoperatoriosgracias al navegador.Resultados. La resección volumétrica tumoral mediafue del 89.1±14.2% del volumen tumoral calculado enlos estudios preoperatorios, con resección total (≥100%)en doce pacientes. En el preoperatorio había focalidadneurológica deficitaria motora en el 58.8% de lospacientes, que aumentó al 76.5% a las 24 horas de lacirugía y se redujo a los 30 días al 41.1%. Hubo una (..) (AU)

Objectives. The role of the microsurgical managementof intrinsic brain tumors is to maximize the volumetricresection of the tumoral tissue minimizing thepostoperative morbidity. The purpose of our paper hasbeen to study the benefits of an original protocol developedfor the microsurgical treatment of tumors locatedin eloquent motor areas where the navigation and electricalstimulation of motor subcortical pathways havebeen implemented.Materials and methods. A total of 17 patients operatedon for resection of cortical or subcortical tumors inmotor areas were included in the series. Preoperativeplanning for multimodal navigation was done integratinganatomic studies, motor functional MRI (f-MRI)and subcortical pathways volumes generated by diffusiontensor imaging (DTI). Intraoperative neuromonitorizationincluded motor mapping by direct corticaland subcortical electrical stimulation (CS and sCS) andlocalization of the central sulcus using cortical multipolarelectrodes and the N20 wave inversion technique.The location of all cortical and subcortical stimulatedpoints with positive motor response was stored in thenavigator and correlated with the cortical or subcorticalmotor functional structures defined preoperatively.Results. The mean tumoral volumetric resection (..) (AU)

Use of basiliximab induction in low-immunological risk renal transplant recipients receiving tacrolimus-based immunosuppression.

Basiliximab induction treatment has been shown to reduce the incidence of acute rejection episodes without the secondary side effects observed with antilymphocyte polyclonal antibodies. We analyzed our experience with basiliximab induction associated with tacrolimus-based immunosuppression among low-immunological risk renal transplant recipients. We retrospectively analyzed 55 renal transplantation patients of low inmunological risk who received organs from donors younger than 55 years. We compared a group of 21 patients (38.9%; group 1) treated with basiliximab (Simulect, Novartis, Basel, Switzerland) with 33 patients (61.1%; group 2) without induction. The patient groups did not differ in recipient age (46.39 +/- 11.1 in group 1 vs 41.82 +/- 11.02 years in group 2; P = .25), donor age (36.71 +/- 14.72 vs 35.09 +/- 14.63 years; P = .69), or recipient and donor gender. No differences were observed in dose or tacrolimus levels during follow-up. The incidences of delayed graft function (DGF; 28.6% vs 28.1%; P = .97) and of acute rejection episodes (9.5% vs 15.6%; P = .52) were similar in both groups. Serum creatinine and proteinuria levels (P > .05) and hospital admissions due to infections (36.4 vs 35.7%; P = .97) were also similar in both groups. At 1 year graft survival rates were 92% and 96% (P = .97) in groups 1 and 2, respectively. Considering our findings and the costs of basiliximab treatment, we conclude that routine administration of basiliximab cannot be justified in young, low-immunological risk transplant recipients undergoing tacrolimus-based immunosuppression.

[Analysis of variability in determining intact parathyroid hormone (iPTH) according to the method used to process the sample]. / Análisis de la variabilidad en la determinación de la hormona paratiroidea (PTH-i) según el método empleado para procesar la muestra.

BACKGROUND: The measurement of i-PTH circulating is not easy due to its analytical variablity. Variability that appears in the process that goes from the sample collection to the final result determination. There are several important aspects that can influence within the pre-test variability: type of sample (serum o plasma), temperature, time elapses from blood extraction to freezing and from freezing to i-PTH quantification. Blood coming from centres far from our laboratory do not always meet the required processing conditions. Our aim was to study the stability of i-PTH with varying conditions of temperature and time until freezing in patients with chronic kidney disease (CKD). METHODS: We have analyzed 294 blood samples of 49 patients with chronic kidney disease (18 transplantated patients (36.7%) and 31 patients in haemodyalisis (63.3%)). The blood samples were collected using tubes treated with ethylenediaminotetraacetic acid (EDTA); these samples were subjected to different conditions of temperature and time before they were frozen, constituting 6 groups: blood centrifuged and plasma immediately frozen (group A or reference group); blood maintained 1 hour at room temperature and plasma stored at 2-8 masculineC during 0, 8 and 24 hours (groups B,C,D); blood maintained 3 hours at room temperature and plasma stored at 2-8 masculineC during 0 and 8 hours (groups E,F). The intact PTH (i-PTH) was measured using the immunoradiometric assay (IRMA Total Intact Scantibodies assay). We have analyzed the differences between the PTH-i mean values in the referenced groud and the others. We have applied the tests of homogeneity variance and normality and we have perform a comparation by pairs with the t-test including the Bonferroni correction. RESULTS: The mean value of intact-PTH in the referente Group was 202.5+/-199.72 pg/ml. The means values of intact-PTH in the other groups were 196 +/- 203.23 pg/ml, 202.8 +/- 200.2 pg/ml, 200.06 +/- 194.87 pg/ml, 204.08 +/- 204.073 pg/ml, 197.94 +/- 182.31 pg/ml. The results were practically identical for each group. We did not find important differences with respect to the reference group (p = 0.87, p = 0,99, p = 0,95, p = 0,96, p = 0,90 when comparing with groups 2a, 2b, 2c, 3a y 3b). CONCLUSIONS: The use of EDTA maintain the PTH stability during a longer period without the necessity of freezing the samples immediately. These results can help to state strategies to management the samples in patients with ERC.

Analysis of variability in determining intact parathyroid hormone (iPTH) according to the method used to process the sample

Background: The measurement of i-PTH circulating is not easy due to its analytical variablity. Variability that appears in the process that goes from the sample collection to the final result determination. There are several important aspects that can influence within the pre-test variability: type of sample (serum o plasma),temperature, time elapses from blood extraction to freezing and from freezing to i-PTH quantification. Blood coming from centres far from our laboratory do not always meet the required processing conditions. Our aim was to study the stability of i-PTH with varying conditions of temperature and time until freezing in patients with chronic kidney disease (CKD). Method: We have analyzed294 blood samples of 49 patients with chronic kidney disease (18 transplantated patients (36.7%) and 31 patients in haemodyalisis (63.3%)). The blood samples were collected using tubes treated with ethylenediamino tetraacetic acid(EDTA); these samples were subjected to different conditions of temperature and time before they were frozen, constituting 6 groups: blood centrifuged and plasma immediately frozen (group A or reference group);blood maintained 1 hour at room temperature and (..) (AU)

Background: The measurement of i-PTH circulating is not easy due to its analytical variablity. Variability that appears in the process that goes from the sample collection to the final result determination. There are several important aspects that can influence within the pre-test variability: type of sample (serum o plasma), temperature, time elapses from blood extraction to freezing and from freezing to i-PTH quantification. Blood coming from centres far from our laboratory do not always meet the required processing conditions. Our aim was to study the stability of i-PTH with varying conditions of temperature and time until freezing in patients with chronic kidney disease (CKD). Method: We have analyzed 294 blood samples of 49 patients with chronic kidney disease (18 transplantated patients (36.7%) and 31 patients in haemodyalisis (63.3%)). The blood samples were collected using tubes treated with ethylenediaminotetraacetic acid (EDTA); these samples were subjected to different conditions of temperature and time before they were frozen, constituting 6 groups: blood centrifuged and plasma immediately frozen (group A or reference group); blood maintained 1 hour at room temperature and plasma stored at 2-8 ºC during 0, 8 and 24 hours (groups B,C,D); blood maintained 3 hours at room temperature and plasma stored at 2-8 ºC during 0 and 8 hours (groups E,F). The intact PTH (i-PTH) was measured using the immunoradiometric assay (IRMA Total Intact Scantibodies assay). We have analyzed the differences between the PTH-i mean values in the referenced groud and the others. We have applied the tests of homogeneity variance and normality and we have perform a comparation by pairs with the t-test including the Bonferroni correction. Results: The mean value of intact- PTH in the referente Group was 202.5±199.72 pg/ml. The means values of intact-PTH in the other groups were 196 ± 203.23 pg/ml, 202.8 ± 200.2 pg/ml, 200.06 ± 194.87 pg/ml, 204.08 ± 204.073 pg/ml, 197.94 ± 182.31 pg/ml. The results were practically identical for each group. We did not find important differences with respect to the reference group (p = 0.87, p = 0,99, p = 0,95, p = 0,96, p = 0,90 when comparing with groups 2a, 2b, 2c, 3a y 3b). Conclusions: The use of EDTA maintain the PTH stability during a longer period without the necessity of freezing the samples immediately. These results can help to state strategies to management the samples in patients with ERC (AU)

Introducción: Las alteraciones del metabolismo óseo-mineral presentan una alta prevalencia en los pacientes con enfermedad renal crónica (ERC), siendo mayor conforme avanza el estadio de enfermedad. El diagnóstico de dichas alteraciones se basa fundamentalmente en la determinación de niveles de hormona paratiroide (PTH-i). Sin embargo, la determinación de esta hormona no es sencilla y está sometida a gran variabilidad. Los métodos para procesar las muestras de PTH-i no están estandarizados, hecho que podría ser una fuente importante de variabilidad preanalítica. Objetivo: Analizar la variabilidad en los resultados de la determinación de la PTH-i comparando distintas formas de procesar la misma muestra de plasma tratado conácido etilendiaminotetraacético (EDTA) en pacientes con ERC. Material y métodos: Se han analizado 294 muestras, correspondientes a 49 pacientes con ERC, 18 procedentes de la Consulta de Trasplante Renal (36,7%) y 31 del programa de Hemodiálisis Crónica de nuestro Centro (63,3%). Se ha procesado la misma muestra de cada uno de nuestros pacientes de seis maneras distintas, comparando las medias entre el grupo de referencia o gold standard y los otros grupos a estudio. Las muestras se procesaron con diferentes condiciones de temperatura y tiempo antes de ser congeladas, constituyendo seis grupos: centrifugación y congelación inmediata (grupo 1, de referencia); muestra a temperatura ambiente una hora, centrifugación y mantenimiento en nevera (2-8 ºC) durante 0, 8 o 24 horas (grupos 2 A, 2B y 2C, respectivamente); mantenimiento de sangre a temperatura ambiente 3 horas, mantenimiento en nevera (2-8 ºC) durante 0 y 8 horas (grupos 3A y 3B). La PTH-i se ha determinado mediante Inmunoradiometria (IRMA Total Intact Scantibodies assay). Se ha realizado el test de homogeneidad de varianzas y normalidad, y depués comparaciones por pares con el t-test con la corrección de Bonferroni. Resultados: La PTH-intacta media en el grupo de referencia fue 202,5 ± 199,72 pg/ml. Las medias de PTH-intacta en distintos grupos analizados fueron 196 ± 203,23 pg/ml, 202,8 ± 200,2 pg/ml, 200,06 ± 194,87 pg/ml, 204,08 ± 204,073 pg/ml, 197,94 ± 182,31 pg/ml. Los resultados fueron prácticamente superponibles, no encontrando diferencias significativas respecto al grupo de referencia (p = 0,87, p = 0,99, p = 0,95, p = 0,96, p = 0,90 al comparar con grupos 2A, 2B, 2C, 3A y 3B, respectivamente). Conclusiones: La utilización de EDTA como conservante en el procesamiento de las muestras analíticas para la determinación sanguínea de PTH-i permite un mayor tiempo de procesamiento de la misma, sin la exigencia de su congelación inmediata, mostrando una mínima variabilidad en los resultados obtenidos según diferentes formas de procesamiento. Estos resultados pueden ayudar a establecer estrategias logísticas para el procesamiento de muestras sanguíneas en los pacientes con ERC (AU)

Induction treatment with low-dose thymoglobulin or basiliximab in renal transplants from older donors.

Transplantation of kidneys from older donors is followed by an increase in delayed graft function (DGF) and acute rejection episodes (ARE). In these circumstances, induction treatment, whether with antithymocyte globulin or with interleukin-2 receptor blockers, may delay the introduction of calcineurin inhibitors (CNI) with effective prevention of ARE. We examined the efficacy and safety of induction treatment with 2 low doses of thymoglobulin compared with 2 doses of basiliximab. A group of 27 patients were treated with thymoglobulin and another 36 with basiliximab. CNI introduction was delayed until day 3 posttransplantation. The thymoglobulin group received 2 doses of 1.25 mg/kg on alternate days and the basiliximab group 2 doses of 20 mg. A trend to a lower incidence of DGF was observed in the thymoglobulin group (33% vs 55.6%; P = .08), with lower levels of serum creatinine on days 7 (P = .02) and 14 (P = .02) posttransplantation. No patient in the thymoglobulin group experienced ARE, but 11 patients (30.6%) in the basiliximab group did (P < .001), and 5 needed rescue treatment with thymoglobulin. We found no differences in the incidence of cytomegalovirus (CMV) disease (P = .945), admission due to infections (P = .274), or neoplasia (P = .340), or differences in graft (P = .69) and patient (P = .21) survivals at 1 and 3 years. Low-dose thymoglobulin was more effective at preventing DGF and ARE in renal transplant recipients of organs from older donors, with no differences in infectious complications or graft and patient survivals.