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BACKGROUND: Delaying the transition from minimal cognitive impairment to Alzheimer's dementia is a major concern in Alzheimer's disease (AD) therapeutics. Pathological signs of AD occur years before the onset of clinical dementia. Thus, long-term therapeutic approaches, with safe, minimally invasive, and yet effective substances are recommended. There is a need to develop new drugs to delay Alzheimer's dementia. We have taken a nutritional supplement approach with genistein, a chemically defined polyphenol that acts by multimodal specific mechanisms. Our group previously showed that genistein supplementation is effective to treat the double transgenic (APP/PS1) AD animal model. METHODS: In this double-blind, placebo-controlled, bicentric clinical trial, we evaluated the effect of daily oral supplementation with 120 mg of genistein for 12 months on 24 prodromal Alzheimer's disease patients. The amyloid-beta deposition was analyzed using 18F-flutemetamol uptake. We used a battery of validated neurocognitive tests: Mini-Mental State Exam (MMSE), Memory Alteration Test (M@T), Clock Drawing Test, Complutense Verbal Learning Test (TAVEC), Barcelona Test-Revised (TBR), and Rey Complex Figure Test. RESULTS: We report that genistein treatment results in a significant improvement in two of the tests used (dichotomized direct TAVEC, p = 0.031; dichotomized delayed Centil REY copy p = 0.002 and a tendency to improve in all the rest of them. The amyloid-beta deposition analysis showed that genistein-treated patients did not increase their uptake in the anterior cingulate gyrus after treatment (p = 0.878), while placebo-treated did increase it (p = 0.036). We did not observe significant changes in other brain areas studied. CONCLUSIONS: This study shows that genistein may have a role in therapeutics to delay the onset of Alzheimer's dementia in patients with prodromal Alzheimer's disease. These encouraging results indicate that this should be followed up by a new study with more patients to further validate the conclusion that arises from this study. TRIAL REGISTRATION: NCT01982578, registered on November 13, 2013.

BACKGROUND: The microvessels area (MVA), derived from microvascular proliferation, is a biomarker useful for high-grade glioma classification. Nevertheless, its measurement is costly, labor-intense, and invasive. Finding radiologic correlations with MVA could provide a complementary non-invasive approach without an extra cost and labor intensity and from the first stage. This study aims to correlate imaging markers, such as relative cerebral blood volume (rCBV), and local MVA in IDH-wildtype glioblastoma, and to propose this imaging marker as useful for astrocytoma grade 4 classification. METHODS: Data from 73 tissue blocks belonging to 17 IDH-wildtype glioblastomas and 7 blocks from 2 IDH-mutant astrocytomas were compiled from the Ivy GAP database. MRI processing and rCBV quantification were carried out using ONCOhabitats methodology. Histologic and MRI co-registration was done manually with experts' supervision, achieving an accuracy of 88.8% of overlay. Spearman's correlation was used to analyze the association between rCBV and microvessel area. Mann-Whitney test was used to study differences of rCBV between blocks with presence or absence of microvessels in IDH-wildtype glioblastoma, as well as to find differences with IDH-mutant astrocytoma samples. RESULTS: Significant positive correlations were found between rCBV and microvessel area in the IDH-wildtype blocks (p < 0.001), as well as significant differences in rCBV were found between blocks with microvascular proliferation and blocks without it (p < 0.0001). In addition, significant differences in rCBV were found between IDH-wildtype glioblastoma and IDH-mutant astrocytoma samples, being 2-2.5 times higher rCBV values in IDH-wildtype glioblastoma samples. CONCLUSIONS: The proposed rCBV marker, calculated from diagnostic MRIs, can detect in IDH-wildtype glioblastoma those regions with microvessels from those without it, and it is significantly correlated with local microvessels area. In addition, the proposed rCBV marker can differentiate the IDH mutation status, providing a complementary non-invasive method for high-grade glioma classification.

Palliative care is referred to a set of programs for patients that suffer life-limiting illnesses. These programs aim to maximize the quality of life (QoL) for the last stage of life. They are currently based on clinical evaluation of the risk of 1-year mortality. The main aim of this work is to develop and validate machine-learning-based models to predict the exitus of a patient within the next year using data gathered at hospital admission. Five machine-learning techniques were applied using a retrospective dataset. The evaluation was performed with five metrics computed by a resampling strategy: Accuracy, the area under the ROC curve, Specificity, Sensitivity, and the Balanced Error Rate. All models reported an AUC ROC from 0.857 to 0.91. Specifically, Gradient Boosting Classifier was the best model, producing an AUC ROC of 0.91, a sensitivity of 0.858, a specificity of 0.808, and a BER of 0.1687. Information from standard procedures at hospital admission combined with machine learning techniques produced models with competitive discriminative power. Our models reach the best results reported in the state of the art. These results demonstrate that they can be used as an accurate data-driven palliative care criteria inclusion.

Prevalence of overweight and obesity are increas- ing in the last decades, and with them, diseases and health conditions such as diabetes, hypertension or cardiovascular diseases. However, hos- pital databases usually do not record such conditions in adults, neither anthropomorfic measures that facilitate their identification.

To evaluate the effects of Process-Reengineering interventions on the Electronic Health Records (EHR) of a hospital over 7 years.

Resumen Objetivos: Las fracturas atípicas de fémur (FAF) son un tipo de fracturas poco frecuentes, a menudo relacionadas con un tratamiento prolongado con bisfosfonatos (BPs). Actualmente no se conocen con exactitud sus mecanismos patogénicos y no hay pruebas para identificar aquellos pacientes con un alto riesgo de sufrir una FAF. El objetivo de este trabajo es investigar las bases genéticas de las FAFs. Material y métodos: Se secuenció el exoma completo de 3 hermanas y de 3 pacientes adicionales no relacionadas, todas tratadas con BPs durante más de 5 años. Se seleccionaron variantes compartidas por las hermanas, de baja frecuencia y potencialmente patogénicas, y se construyó una red de interacciones de genes y proteínas con los datos hallados. Resultados: Identificamos 37 variantes raras (en 34 genes) compartidas por las 3 hermanas, algunas de ellas no descritas anteriormente. La variante más llamativa fue la mutación p.Asp188Tyr en el enzima geranilgeranil pirofosfato sintasa (codificada por el gen GGPS1), de la vía del mevalonato y esencial para la función del osteoclasto. Otro hallazgo interesante fueron dos mutaciones (una en las 3 hermanas y una en una paciente no relacionada) en el gen CYP1A1, implicado en el metabolismo de los esteroides. Identificamos otras variantes que también podrían estar involucradas en la susceptibilidad a las FAFs o en el fenotipo osteoporótico subyacente, tales como las presentes en los genes SYDE2, NGEF. COG4 y la FN1. Conclusiones: Nuestros datos son compatibles con un modelo donde la acumulación de variantes de susceptibilidad podría participar en la base genética de las FAFs. Abstract Objectives: Atypical femoral fractures (AFF) are rare, often related to long-term bisphosphonate (BPs) treatment. Their pathogenic mechanisms are not precisely known and there is no evidence to identify patients with a high risk of AFF. The aim of this work is to study the genetic bases of AFFs. Materials and methods: Whole-exome sequencing was carried out on 3 sisters and 3 unrelated additional patients, all treated with BPs for more than 5 years. Low frequency, potentially pathogenic variants shared by the 3 sisters, were selected, were selected and a network of gene and protein interactions was constructed with the data found. Results: We identified 37 rare variants (in 34 genes) shared by the 3 sisters, some not previously described. The most striking variant was the p.Asp188Tyr mutation in the enzyme geranylgeranyl pyrophosphate synthase (encoded by the GGPS1 gene), from the mevalonate pathway and essential for osteoclast function. Another noteworthy finding was two mutations (one in the 3 sisters and one in an unrelated patient) in the CYP1A1 gene, involved in the metabolism of steroids. We identified other variants that could also be involved in the susceptibility to AFFs or in the underlying osteoporotic phenotype, such as those present in the SYDE2, NGEF, COG4 and FN1 genes. Conclusions: Our data are compatible with a model where the accumulation of susceptibility variants could participate in the genetic basis of AFFs.

BACKGROUND: A cadaveric feasibility study was carried out. Osteotomies to correct fixed sagittal imbalance are usually performed at L3/ L4. OBJECTIVE: To investigate the feasibility of S1 pedicle subtraction osteotomy to correct spinal deformity and spinopelvic parameters, achieving better results with more limited exposure. The data obtained will allow a fixation construct specific for this osteotomy to be designed. METHODS: S1 pedicle subtraction osteotomy was performed on 12 cadaveric specimens. Baseline and postprocedural computed tomography and biomechanical studies were performed. Data were analyzed with a fixation system SolidWorks model, and the redesigned fixation construct was described and analyzed with an ANSYS model. RESULTS: S1 pedicle subtraction osteotomy is technically feasible. The fixation can be achieved with L4, L5, and iliac screws connected with bars. The system can be reinforced with a polyetheretherketone cage placed anteriorly in the S1 body osteotomy site, a cross-connecting bar, a double iliac screw, or an anterior interbody cage placed at the L5-S1 disc. The fixation strength is improved by angulating the iliac rod channel 10°, adding a semi-sphere to the locking screw contact surface and 2 fins to its saddle. The redesigned construct showed suitable stress and deformation levels, achieving the expected biomechanical requirements. DISCUSSION: Compared with surgery on higher levels, S1 pedicle subtraction osteotomy allows greater correction with shorter fixation, because the osteotomy is performed at a more caudal level, modifying the spinopelvic parameters. CONCLUSIONS: S1 pedicle subtraction osteotomy is technically feasible. Finite element analysis results indicate that it has appropriate biomechanical properties.

Objective: The intravesical administration of hazardous drug products is a standard practice in the urology setting, which potentially exposing medical personnel to these drug products. It was deemed necessary to have a consensus document among the scientific societies involved (the Spanish Urological Association and the Spanish Society of Hospital Pharmacy) that collects the best available evidence on the safest handling possible of dangerous drug products in the setting of urology departments. Method: We reviewed the legislation and recommendations on the handling of dangerous drug products, both at the national and international level. Results: There is national legislation and regulations for protecting workers who handle dangerous drugs and products, as well as recommendations for handling to protect both the product and workers. Discussion: Following the strategic lines of the European Parliament for 2014-2020 in the chapter on occupational safety and health, the Spanish Urological Association and the Spanish Society of Hospital Pharmacy proposed a series of actions that decrease the risks of exposure for practitioners and caregivers involved in the handling of these products. Conclusions: After this review, 19 recommendations were established for handling dangerous drug products, which can be summarised as the need to train all individuals involved (from management teams to patients and caregivers), adopt systems that prevent contaminating leaks, implement exposure surveillance programmes and optimise available resources.

Background: The objective of this study was to investigate the long-term impact of low-level viremia (LLV) on all-cause mortality, AIDS and non-AIDS events (NAEs), and virological failure in patients receiving antiretroviral therapy (ART). Methods: We analyzed ART-naive adults from the cohort of the Spanish AIDS Research Network (CoRIS) who initiated ART from 2004 to 2015 and achieved plasma viral load (VL) below 50 copies per milliliter. LLV50-199 was defined as 2 consecutive VL between 50 and 199 copies per milliliter, and LLV200-499 as 2 consecutive VL between 50 and 499 copies per milliliter with at least one between 200 and 499 copies per milliliter. Multivariable Cox models were used to estimate the association of LLV with AIDS events/death, non-AIDS events, and virological failure. Results: Of 5986 patients included, 237 (4.0%) experienced LLV50-199 and 168 (2.8%) developed LLV200-499. One hundred seventy-one patients died or developed an AIDS event, 245 had any serious NAE and 280 had virological failure. LLV200-499 was strongly associated with a higher risk of both AIDS events/death [adjusted hazard ratio (aHR), 2.89; 95% confidence interval (CI), 1.41 to 5.92] and virological failure (aHR, 3.25; 95% CI: 1.77 to 5.99), whereas no differences were observed between LLV50-199 and no LLV neither for AIDS events/death (aHR, 1.84; 95% CI: 0.89 to 3.82) nor virological failure (aHR, 1.42; 95% CI: 0.78 to 2.58). LLV was not associated with the occurrence of any serious NAE. Conclusions: In this cohort, LLV200-499 was strongly associated with AIDS events/death and virological failure, but not with any serious NAE. Therefore, vigorous treatment should be implemented in patients with more than 200 copies per milliliter.

Atypical femoral fractures (AFFs) are a rare but potentially devastating event, often but not always linked to bisphosphonate (BP) therapy. The pathogenic mechanisms underlying AFFs remain obscure, and there are no tests available that might assist in identifying those at high risk of AFF. We previously used exome sequencing to explore the genetic background of three sisters with AFFs and three additional unrelated AFF cases, all previously treated with BPs. We detected 37 rare mutations (in 34 genes) shared by the three sisters. Notably, we found a p.Asp188Tyr mutation in the enzyme geranylgeranyl pyrophosphate synthase, a component of the mevalonate pathway, which is critical to osteoclast function and is inhibited by N-BPs. In addition, the CYP1A1 gene, responsible for the hydroxylation of 17ß-estradiol, estrone, and vitamin D, was also mutated in all three sisters and one unrelated patient. Here we present a detailed list of the variants found and report functional analyses of the GGPS1 p.Asp188Tyr mutation, which showed a severe reduction in enzyme activity together with oligomerization defects. Unlike BP treatment, this genetic mutation will affect all cells in the carriers. RNAi knockdown of GGPS1 in osteoblasts produced a strong mineralization reduction and a reduced expression of osteocalcin, osterix, and RANKL, whereas in osteoclasts, it led to a lower resorption activity. Taken together, the impact of the mutated GGPPS and the relevance of the downstream effects in bone cells make it a strong candidate for AFF susceptibility. We speculate that other genes such as CYP1A1 might be involved in AFF pathogenesis, which remains to be functionally proved. The identification of the genetic background for AFFs provides new insights for future development of novel risk assessment tools. © 2018 American Society for Bone and Mineral Research.

Background: The optimal dosage of cryotherapy during cryoballoon ablation of pulmonary veins is still unclear. This trial tested the noninferiority of a novel, individualized, cryotherapy-dosing strategy for each vein. Methods and Results: This prospective, randomized, multicenter, noninferiority study included 140 patients with paroxysmal atrial fibrillation, which was refractory to antiarrhythmic drugs. Patients were randomly assigned to a conventional strategy of 180-second cryoballoon applications per vein with a bonus freeze (control group, n=70) or to a shorter-time application protocol, with 1 application that lasted the time required for electric block time to effect plus 60- and a 120-second freeze bonus (study group, n=70). Patients were followed with a long-term monitoring system of 30 days. At 1-year follow-up, no difference was observed in terms of free atrial fibrillation-recurrence rates: 79.4% in control versus 78.3% in study group (Delta=1.15%; 90% confidence interval, -10.33% to 12.63%; P=0.869). Time to effect was detected in 72.1% of veins. The control and study groups had similar mean number of applications per patient (9.62 versus 9.92.4; P=0.76). Compared with controls, the study group had a significantly shorter cryotherapy time (28.3 +/- 7 versus 19.4 +/- 4.3 minutes; P

Introduction: Little is known about the prevalence of electrical storm, baseline characteristics and mortality implications of patients with implantable cardioverter defibrillator in primary prevention versus those patients without electrical storm. We sought to assess the prevalence, baseline risk profile and survival significance of electrical storm in patients with implantable defibrillator for primary prevention. Methods: Retrospective multicenter study performed in 15 Spanish hospitals. Consecutives patients referred for desfibrillator implantation, with or without left ventricular lead (at least those performed in 2010 and 2011), were included. Results: Over all 1,174 patients, 34 (2,9%) presented an electrical storm, mainly due to ventricular tachycardia (82.4%). There were no significant baseline differences between groups, with similar punctuation in the mortality risk scores (SHOCKED, MADIT and FADES). A clear trigger was identified in 47% of the events. During the study period (38 +/- 21 months), long-term total mortality (58.8% versus 14.4%, p < 0.001) and cardiac mortality (52.9% versus 8.6%, p < 0.001) were both increased among electrical storm patients. Rate of inappropriate desfibrillator intervention was also higher (14.7 versus 8.6%, p < 0.001). Conclusions: In the present study of patients with desfibrillator implantation for primary prevention, prevalence of electrical storm was 2.9%. There were no baseline differences in the cardiovascular risk profile versus those without electrical storm. However, all cause mortality and cardiovascular mortality was increased in these patients versus control desfibrillator patients without electrical storm, as was the rate of inappropriate desfibrillator intervention. (C) 2015 Instituto Nacional de Cardiologia Ignacio Chavez. Published by Masson Doyma Mexico S.A. All rights reserved.

Currently, there continues to be a lack of evidence regarding outcomes associated with device-based therapy for ventricular arrhythmias in elderly patients, even more in primary-prevention indications. We aimed to describe the follow-up in terms of efficacy and safety of implantable cardioverter-defibrillator (ICD) therapy in a large cohort of elderly patients. Retrospective multicentre study performed in 15 Spanish hospitals. Consecutive patients referred for ICD implantation before 2011 were included. One hundred and sixty-two of 1174 patients (13.8%) a parts per thousand yen75 years were considered as 'elderly'. When compared with those patients < 75, this subgroup presented more co-morbid conditions, including hypertension, chronic obstructive pulmonary disease , and renal failure, and more previous hospitalizations due to heart failure (HF). During a mean follow-up of 104.4 +/- 3.3 months, 162 patients (14%) died, 120 in the younger age (12.4%), and 42 (24.4%) in the elderly. Kaplan-Meier analysis showed an increased probability of death with increasing age (17, 24, 28, and 69% at 12, 24, 48, and 60 months of follow-up in the elderly group). There was neither difference regarding the rate of appropriate nor inappropriate ICD intervention. In a real-world scenario, elderly patients comprise similar to 15% of ICD implantations for primary prevention of sudden cardiac death (SCD). Although the rate of appropriate therapy is similar between groups, the benefit of ICD is attenuated for a major increase in mortality risk among those patients a parts per thousand yen75 years at the moment of device implantation.

Background Epicardial ablation has shown improvement in clinical outcomes of patients with ischemic heart disease (IHD) after ventricular tachycardia (VT) ablation. However, usually epicardial access is only performed when endocardial ablation has failed. Our aim was to compare the efficacy of endocardial+epicardial ablation versus only endocardial ablation in the first procedure in patients with IHD. Methods and Results Fifty-three patients with IHD, referred for a first VT ablation to our institution, from 2012 to 2014, were included. They were divided in 2 groups according to enrollment time: from May 2013, we started to systematically perform endo-epicardial access (Epi-Group) as first-line approach in consecutive patients with IHD (n=15). Patients who underwent only an endocardial VT ablation in their first procedure (Endo-Group) included patients with previous cardiac surgery and the historical (before May 2013; n=35). All late-potentials in the scar zone were eliminated, and if VT was tolerated, critical isthmuses were also approached. The end point was the noninducibility of any VT. During a median follow-up of 1510 months, the combined end point (hospital or emergency admission because of a ventricular tachycardia or reablation) occurred in 14 patients of the Endo-group and in one patient in the Epi-group (event-free survival curves by Grey-test, P=0.03). Ventricular arrhythmia recurrences occurred in 16 and in 3 patients in the Endo and Epi-Group, respectively (Grey-test, P=0.2). Conclusions A combined endocardial-epicardial ablation approach for initial VT ablation was associated with fewer readmissions for VT and repeat ablations. Further studies are warranted.

Automatic brain tumour segmentation has become a key component for the future of brain tumour treatment. Currently, most of brain tumour segmentation approaches arise from the supervised learning standpoint, which requires a labelled training dataset from which to infer the models of the classes. The performance of these models is directly determined by the size and quality of the training corpus, whose retrieval becomes a tedious and time-consuming task. On the other hand, unsupervised approaches avoid these limitations but often do not reach comparable results than the supervised methods. In this sense, we propose an automated unsupervised method for brain tumour segmentation based on anatomical Magnetic Resonance (MR) images. Four unsupervised classification algorithms, grouped by their structured or non-structured condition, were evaluated within our pipeline. Considering the non-structured algorithms, we evaluated K-means, Fuzzy K-means and Gaussian Mixture Model (GMM), whereas as structured classification algorithms we evaluated Gaussian Hidden Markov Random Field (GHMRF). An automated postprocess based on a statistical approach supported by tissue probability maps is proposed to automatically identify the tumour classes after the segmentations. We evaluated our brain tumour segmentation method with the public BRAin Tumor Segmentation (BRATS) 2013 Test and Leaderboard datasets. Our approach based on the GMM model improves the results obtained by most of the supervised methods evaluated with the Leaderboard set and reaches the second position in the ranking. Our variant based on the GHMRF achieves the first position in the Test ranking of the unsupervised approaches and the seventh position in the general Test ranking, which confirms the method as a viable alternative for brain tumour segmentation.

Fundamento. En los ultimos anos se han desarrollado un gran numero de tecnicas para estimar la densidad mineral osea y con ello poder realizar el diagnostico de osteoporosis. Sin embargo, invariablemente se aplican los criterios diagnosticos que fueron establecidos por la OMS para su utilizacion con la densitometria radiologica dual (DEXA), lo cual podria no ser correcto en el caso de los ultrasonidos. Metodo. Se estudio a una poblacion escogida aleatoriamente de 2.589 personas de ambos sexos, 1.138 varones y 1.451 mujeres de entre 10 y 99 anos de edad procedente de 11 provincias espanolas. Se efectuo una medicion de los parametros que estima el ultrasonografo de calcaneo Sahara®, Hologic®: velocidad del sonido, (SOS), coeficiente de atenuacion de banda ancha (BUA), indice de consistencia (QUI) y densidad mineral osea estimada (est. DMO). Se calculo la prevalencia de osteopenia y osteoporosis aplicando los criterios de la OMS (osteopenia: Tscore = 1 y osteoporosis Tscore = 2,5) y la prevalencia de osteoporosis efectuando el corte en un Tscore de ­1,8. Resultados. Empleando los criterios de la OMS, existe osteoporosis (Tscore = 2,5) en el 1,5 % de los varones y el 5,9 % de las mujeres de entre 51 y 70 anos y en el 2,6 % de los varones y el 22,1 % de las mujeres de mas de 70 anos. Si efectuamos el corte en un Tscore de ­1,8, la prevalencia asciende al 8,2 % de los varones y 21,9 % de las mujeres de entre 51 y 70 anos y al 8,4 % de los varones y 40,9% de las mujeres de mas de 70 anos. Conclusion. La prevalencia de osteoporosis en la poblacion espanola de ambos sexos difiere notablemente aplicando el punto de corte en un Tscore de ­2,5 como indica la OMS o en ­1,8 sugerido por otros autores. Es necesario la realizacion de un consenso para establecer cual es el punto de corte apropiado para el diagnostico de osteoporosis por ultrasonografia cuantitativa de calcaneo. Palabras clave: ultrasonidos, calcaneo, prevalencia, osteoporosis, osteopenia, criterios OMS.

The effect of high-flux hemodialysis membranes on patient survival has not been unequivocally determined. In this prospective, randomized clinical trial, we enrolled 738 incident hemodialysis patients, stratified them by serum albumin < or = 4 and >4 g/dl, and assigned them to either low-flux or high-flux membranes. We followed patients for 3 to 7.5 yr. Kaplan-Meier survival analysis showed no significant difference between high-flux and low-flux membranes, and a Cox proportional hazards model concurred. Patients with serum albumin < or = 4 g/dl had significantly higher survival rates in the high-flux group compared with the low-flux group (P = 0.032). In addition, a secondary analysis revealed that high-flux membranes may significantly improve survival of patients with diabetes. Among those with serum albumin < or = 4 g/dl, slightly different effects among patients with and without diabetes suggested a potential interaction between diabetes status and low serum albumin in the reduction of risk conferred by high-flux membranes. In summary, we did not detect a significant survival benefit with either high-flux or low-flux membranes in the population overall, but the use of high-flux membranes conferred a significant survival benefit among patients with serum albumin < or = 4 g/dl. The apparent survival benefit among patients who have diabetes and are treated with high-flux membranes requires confirmation given the post hoc nature of our analysis.

Cardiac allograft vasculopathy (CAV) is the main cause of graft failure and death 1 year after heart transplantation (HTx). Metabolic syndrome (MS) increases the risk of cardiovascular events by endothelial dysfunction. The purpose of this study was to determine if patients with MS developed a higher risk of CAV 1 year after HTx.

OBJECTIVES To study the clinical, diagnostic, and therapeutic features of upper urinary tract tumors. METHODS We perform a retrospective study of upper urinary tract tumors treated in our Department at Clinica La Luz Madrid between 1995 and 2008. RESULTS We treated 42 tumors in 40 patients. Mean age was 64 years; there were 29 males and 11 females. Macroscopic hematuria was the most frequent clinical presentation, in 45% of the cases, and the imaging diagnostic test most frequently used was intravenous urogram (62,5%).There were more tumors on the right side (20 cases( than the left side (18 case), 2 cases were bilateral. Distal ureter was the most frequent site.27,5% of the patients presented associated bladder tumors. The most frequently used therapy was laser endoscopic resection. 5 patients required a second operation due to recurrence and 2 more a programmed second procedure due to incomplete resection; 7 cases presented postoperative complications. 70%of the tumors were superficial. 40%of the cases underwent local chemotherapy with weekly bladder instillations of Mitomycin C for 8 weeks. Recurrence rate was 20% and mortality 10%. CONCLUSIONS Upper urinary tract tumors keep being a rare entity appearing in mid-advanced ages. Radical nephroureterectomy with excision of bladder cuff has been the treatment of choice for years, but in recent years endoscopic treatment is gaining more importance and is showing good results in selected cases.

Background: The Spanish Back Pain Research Network (REIDE) brings together teams of researchers and clinicians who are interested in nonspecific neck and back pain (BP). Its objective is to improve the efficacy, safety, effectiveness, and efficiency of the clinical management of BP. Method: The Network welcomes clinicians and researchers interested in BP. The only requirement to become a member of REIDE is to take part in one of its research projects, and any member can propose a new one. The Network supports those projects that are of interest to two or more groups by assuming their administration and management, which allows the researchers to focus on their task. Its working method ensures methodological quality, a multidisciplinary approach, and the clinical relevance of those projects that are carried out. Results: 179 researchers from 11 areas in Spain are involved in REIDE, including experts in all of the relevant fields of BP research. Most Spanish studies on BP that have been published in international scientific journals come from the teams involved in REIDE, and it currently has 13 ongoing research projects. Conclusions: The Network can help to enhance research among rehabilitation specialists who are interested in BP, and can contribute to the development of research projects which are of interest to the specialty. © 2005 Sociedad Española de Rehabilitación y Medicina Física (SERMEF) y Elsevier España, S.L.

The aim of the present study was to study salt and water metabolism in thyroid deficiency. We performed an oral water loading test (OWL) and a hypertonic 5% saline infusion test (HSI) in 16 patients with overt primary hypothyroidism before replacement treatment (PRE group) and after, in eight patients with subclinical hypothyroidism (SUB group) and in 16 normal individuals (CG group). In the PRE group, a lower free water clearance was detected in the OWL (P < 0.022), with lower plasma osmolality (OWL: P < 0.005; HSI: P < 0.001) and arginine vasopressin (AVP) (OWL: P < 0.001; HSI: P < 0.001) than the CG group, across both tests; they normalized with the replacement treatment. The same plasma abnormalities were detected in the SUB group with the HSI. Although the AVP and thirst thresholds did not differ between the groups, the lag between them was lower in the PRE (4.1+/-3.2 mOsm/kg) and SUB group (2.6+/-2.1 mOsm/kg) than in the CG group (13.3+/-9.2 mOsm/kg) (P < 0.05). There were no differences in atrial natriuretic hormone (ANH), plasma renin activity (PRA) and plasma aldosterone among the groups. These results indicate that plasma hypo-osmolality and low levels of AVP are present in primary hypothyroidism, and indeed are already present in the subclinical phase of the disease. An overlap between the thresholds of thirst and AVP seem to play a role in these abnormalities, but ANH, PRA and plasma aldosterone do not appear to contribute.