Extinction of herbivorous dinosaurs linked to Early Jurassic global warming event.

Sauropods, the giant long-necked dinosaurs, became the dominant group of large herbivores in terrestrial ecosystems after multiple related lineages became extinct towards the end of the Early Jurassic (190-174 Ma). The causes and precise timing of this key faunal change, as well as the origin of eusauropods (true sauropods), have remained ambiguous mainly due to the scarce dinosaurian fossil record of this time. The terrestrial sedimentary successions of the Cañadón Asfalto Basin in central Patagonia (Argentina) document this critical interval of dinosaur evolution. Here, we report a new dinosaur with a nearly complete skull that is the oldest eusauropod known to date and provide high-precision U-Pb geochronology that constrains in time the rise of eusauropods in Patagonia. We show that eusauropod dominance was established after a massive magmatic event impacting southern Gondwana (180-184 Ma) and coincided with severe perturbations to the climate and a drastic decrease in the floral diversity characterized by the rise of conifers with small scaly leaves. Floral and faunal records from other regions suggest these were global changes that impacted the terrestrial ecosystems during the Toarcian warming event and formed part of a second-order mass extinction event.

Outcomes of an enhanced recovery after radical cystectomy program in a prospective multicenter study: compliance and key components for success.

OBJECTIVE: To investigate the effect of an Enhanced Recovery After Surgery (ERAS) program on complications and length of stay (LOS) after radical cystectomy (RC) and to assess if the number and type of components of ERAS play a key role on the decrease of surgical morbidity. MATERIALS AND METHODS: We analyzed the data of 277 patients prospectively recruited in 11 hospitals undergoing RC initially managed according to local practice (Group I) and later within an ERAS program (Group II). Two main outcomes were defined: 90-day complications rate and LOS. As secondary variables we studied 90-day mortality, 30-day readmission and transfusion rate. RESULTS: Patients in Group II had a higher use of ERAS measures (98.6%) than those in Group I (78.2%) (p < 0.05). Patients in Groups I and II experienced similar complications (70.5% vs. 66%, p = 0.42). LOS was not different between Groups I and II (12.5 and 14 days, respectively, p = 0.59). The risk of having any complication decreases for patients having more than 15 ERAS measures adopted [RR = 0.815; 95% confidence interval (CI) 0.667-0.996; p = 0.045]. Avoidance of transfusion and nasogastric tube, prevention of ileus, early ambulation and a fast uptake of a regular diet are independently associated with the absence of complications. CONCLUSIONS: Complications and LOS after RC were not modified by the introduction of an ERAS program. We hypothesize that at least 15 measures should be applied to maximize the benefit of ERAS.

Nox1-derived oxidative stress as a common pathogenic link between obesity and hyperoxaluria-related kidney injury.

Specific relationships among reactive oxygen species, activation pathways, and inflammatory mechanisms involved in kidney injury were assessed in a combined model of obesity and hyperoxaluria. Male Wistar rats were divided into four groups: Control, HFD (high fat diet), OX (0.75% ethylene glycol), and HFD + OX (combined model) Changes in basal O2- levels were evaluated by chemiluminescence in renal interlobar arteries and renal cortex. Furthermore, the effect of different inhibitors on NADPH-stimulated O2- generation was assessed in renal cortex. Oxidative stress sources, and local inflammatory mediators, were also determined, in parallel, by RT-PCR, and correlated with measures of renal function, urinary biochemistry, and renal structure. Rats from the HFD group developed overweight without lipid profile alteration. Tubular deposits of crystals were seen in OX and severely enhanced in HFD + OX groups along with a significantly higher impairment of renal function. Basal oxidative stress was increased in renal cortex of OX rats and in renal arteries of HFD rats, while animals from the combined HFD + OX group exhibited the highest levels of oxidative stress in renal cortex, derived from xanthine oxidase and COX-2. NADPH oxidase-dependent O2- generation was elevated in renal cortex of the OX group and markedly enhanced in the HFD + OX rats, and associated to an up-regulation of Nox1 and a down-regulation of Nox4 expression. High levels of oxidative stress in the kidney, of OX and HFD + OX groups were also associated to an inflammatory response mediated by an elevation of TNFα, COX-2, NFκB1 MCP-1, and OPN. Oxidative stress is a key pathogenic factor in renal disease associated to hyperoxaluria and a common link underlying the exacerbated inflammatory response and kidney injury found under conditions of both obesity and hyperoxaluria. Nox1 pathway must be considered as a potential therapeutic target.

Documento nacional de recomendaciones sobre el seguimiento del paciente con carcinoma de células renales / National recommendations document on the follow-up of patients with renal cell carcinoma

Objetivos: Este documento se ha desarrollado con el objetivo de establecer unas directrices para el seguimiento de los pacientes con carcinoma de células renales (CCR), basadas en la mejor evidencia científica disponible y en la opinión de expertos, que puedan facilitar a los urólogos la toma de decisiones, así como una normalización de criterios a nivel nacional. Material y métodos: La metodología utilizada se basó en el método RAND/UCLA. Un panel de 9 expertos en CCR participaron en el diseño de un índice temático, en la identificación y lectura de la evidencia disponible, y en la formulación de recomendaciones y redacción del contenido. Un grupo validador de 25 expertos, que no había participado en las fases previas, valoró las recomendaciones mediante una votación anónima en una reunión presencial de consenso. Las recomendaciones que alcanzaron el acuerdo del 75% o más de los participantes en dicha votación fueron aceptadas como consenso; las recomendaciones que obtuvieron un acuerdo inferior fueron rechazadas. Resultados: Un total de 25 recomendaciones fueron aceptadas como consenso. En ellas se recogen las pruebas analíticas, pruebas de evaluación clínica y de imagen que deben realizarse en los pacientes con CCR. Las recomendaciones presentadas han sido adaptadas dependiendo del riesgo de recaída. En el actual documento también se detalla la frecuencia y duración del seguimiento para cada perfil de paciente. Conclusiones: El documento actual permite estandarizar los criterios de seguimiento de los pacientes con CCR atendidos en el ámbito del sistema sanitario español, según su riesgo de recaída

Objectives: This document was developed to establish directives for the follow-up of patients with renal cell carcinoma (RCC) based on the best available scientific evidence and on expert opinions, which can help urologists in the decision-making process and standardise the criteria at the national level. Material and methods: The methodology is based on the RAND/UCLA method. A panel of 9 experts on RCC participated in designing a thematic index, identifying and reading the available evidence, formulating recommendations and drafting the content. A validating group of 25 experts, who did not participate in the previous phases, assessed the recommendations through anonymous voting in a face-to-face consensus meeting. The recommendations that were agreed upon by 75% or more of the participants in this vote were accepted as consensus. The recommendations that did not achieve this consensus were rejected. Results: A total of 25 recommendations were accepted as consensus. These recommendations cover the laboratory tests, clinical assessment tests and imaging tests that should be performed for patients with RCC. The presented recommendations have been adapted according to relapse risk. The current document also outlines the frequency and duration of follow-up for each patient profile. Conclusions: The current document enables standardisation of the follow-up criteria for patients with RCC treated in the Spanish healthcare setting, according to the patients' relapse risk

National recommendations document on the follow-up of patients with renal cell carcinoma. / Documento nacional de recomendaciones sobre el seguimiento del paciente con carcinoma de células renales.

OBJECTIVES: This document was developed to establish directives for the follow-up of patients with renal cell carcinoma (RCC) based on the best available scientific evidence and on expert opinions, which can help urologists in the decision-making process and standardise the criteria at the national level. MATERIAL AND METHODS: The methodology is based on the RAND/UCLA method. A panel of 9 experts on RCC participated in designing a thematic index, identifying and reading the available evidence, formulating recommendations and drafting the content. A validating group of 25 experts, who did not participate in the previous phases, assessed the recommendations through anonymous voting in a face-to-face consensus meeting. The recommendations that were agreed upon by 75% or more of the participants in this vote were accepted as consensus. The recommendations that did not achieve this consensus were rejected. RESULTS: A total of 25 recommendations were accepted as consensus. These recommendations cover the laboratory tests, clinical assessment tests and imaging tests that should be performed for patients with RCC. The presented recommendations have been adapted according to relapse risk. The current document also outlines the frequency and duration of follow-up for each patient profile. CONCLUSIONS: The current document enables standardisation of the follow-up criteria for patients with RCC treated in the Spanish healthcare setting, according to the patients' relapse risk.

Metabolic syndrome contributes to renal injury mediated by hyperoxaluria in a murine model of nephrolithiasis.

Metabolic syndrome (MS) individuals have a higher risk of developing chronic kidney disease through unclear pathogenic mechanisms. MS has been also related with higher nephrolithiasis prevalence. To establish the influence of MS on renal function, we designed a murine model of combined metabolic syndrome and hyperoxaluria. Four groups of male Sprague-Dawley rats were established: (1) control group (n = 10) fed with standard chow; (2) stone former group (SF) (n = 10) fed with standard chow plus 0.75% ethylene glycol administered in the drinking water; (3) metabolic syndrome group (MS) (n = 10), fed with 60% fructose diet; (4) metabolic syndrome + stone former group (MS + SF) (n = 10), 60% fructose diet and 0.75% EG in the drinking water. MS group showed a significant injury to renal function when hyperoxaluria was induced. It was demonstrated by a significant decrease of creatinine clearance (p < 0.001), with higher tubular damage (34.3%, CI 95% 23.9-44.7, p < 0.001), produced by deposition of crystals, and increased tubular synthesis of osteopontin as a response to tubular damage. Induction of hyperoxaluria in rats with MS causes severe morphological alterations with a significant impairment of renal function. This impairment is not produced in rats without MS. Therefore, this model can be useful for the study of the influence of MS in stone formation.

GeRNet: a gene regulatory network tool.

Gene regulatory networks (GRNs) are crucial in every process of life since they govern the majority of the molecular processes. Therefore, the task of assembling these networks is highly important. In particular, the so called model-free approaches have an advantage modeling the complexities of dynamic molecular networks, since most of the gene networks are hard to be mapped with accuracy by any other mathematical model. A highly abstract model-free approach, called rule-based approach, offers several advantages performing data-driven analysis; such as the requirement of the least amount of data. They also have an important ability to perform inferences: its simplicity allows the inference of large size models with a higher speed of analysis. However, regarding these techniques, the reconstruction of the relational structure of the network is partial, hence incomplete, for an effective biological analysis. This situation motivated us to explore the possibility of hybridizing with other approaches, such as biclustering techniques. This led to incorporate a biclustering tool that finds new relations between the nodes of the GRN. In this work we present a new software, called GeRNeT that integrates the algorithms of GRNCOP2 and BiHEA along a set of tools for interactive visualization, statistical analysis and ontological enrichment of the resulting GRNs. In this regard, results associated with Alzheimer disease datasets are presented that show the usefulness of integrating both bioinformatics tools.

GPR91 deficiency exacerbates allergic contact dermatitis while reducing arthritic disease in mice.

BACKGROUND: Succinate, in addition to its role as an intermediary of the citric acid cycle, acts as an alarmin, initiating and propagating danger signals resulting from tissue injury or inflammatory stimuli. The contribution of this immune sensing pathway to the development of allergic and inflammatory responses is unknown. METHODS: Ear thickness of wild-type (wt) and Sucnr1-deficient (Sucnr1-/- ) mice, sensitized and challenged with oxazolone, was used as a criterion to assess the relevance of SUCNR1/GPR91 expression mediating allergic contact dermatitis (ACD). Results obtained in this system were contrasted with data generated using passive cutaneous anaphylaxis, ovalbumin-induced asthma and arthritis models. RESULTS: We found augmented ACD reactions in Sucnr1-/- mice. This observation correlated with increased mast cell activation in vitro and in vivo. However, exacerbated mast cell activation in Sucnr1-/- mice did not contribute to the enhancement of asthma or arthritis and seemed to be due to alterations during mast cell development as augmented mast cell responses could be recapitulated in wt mast cells differentiated in the absence of succinate. CONCLUSIONS: A deficiency in succinate sensing during mast cell development confers these cells with a hyperactive phenotype. Such a phenomenon does not translate into exacerbation of asthma or mast cell-dependent arthritis. On the contrary, the fact that Sucnr1-/- mice developed reduced arthritic disease, using two different in vivo models, indicates that GPR91 antagonists may have therapeutic potential for the treatment of allergic and autoimmune diseases.

Urología en la universidad europea: Adaptaciones a Bolonia. El modelo de la Universidad Autónoma de Madrid / Urology at the European university: Adaptations to the Bologna Plan. The model of the Autonomous University of Madrid

El Plan de Convergencia de Bolonia tiene como objetivo fundamental normalizar, armonizar y estandarizar la enseñanza de Medicina en las facultades médicas europeas, imponiendo un curriculum similar. Esto ha supuesto la presencia de la Urología como disciplina universitaria en todas las escuelas médicas europeas. Simultáneamente ha modificado las técnicas pedagógicas y las distribuciones temáticas, insistiendo en la enseñanza práctica y en la activa participación del estudiante en la adquisición de conocimientos y habilidades. Todo ello realza la presencia curricular de la Urología y obliga a una mayor dedicación del profesorado que ahora, en un tiempo limitado presencial y de aulas, tiene que informar y formar al estudiante de Medicina sobre el amplísimo compromiso asistencial de la Urología como especialidad médico-quirúrgica. La adaptación a Bolonia de las numerosas escuelas médicas europeas plantea ciertas dificultades que pueden ser fácilmente superadas, como puede verse en el plan diseñado en la Facultad de Medicina en la Universidad Autónoma de Madrid

The fundamental objective of the Convergence Plan of Bologna is to normalize, harmonize and standardize the teaching of medicine in European medical schools by implementing a similar curriculum. This objective assumes the presence of Urology as a university discipline in all European medical schools. At the same time, the teaching techniques and subject distributions have been modified, emphasizing practical teaching and active participation of the student in the acquisition of expertise and skills. This approach enhances the curricular presence of Urology and requires increased dedication from the teaching staff. These staff members, with limited face-to-face and classroom time, must inform and educate medical students on the broad healthcare commitment of urology as a surgical/medical specialty. The adaptation of the numerous European medical schools to the Bologna Plan raises a number of problems that can be easily overcome, as can be seen in the plan designed by the Faculty of Medicine at the Universidad Autonoma de Madrid

Urology at the European university: adaptations to the Bologna Plan. The model of the Autonomous University of Madrid.

The fundamental objective of the Convergence Plan of Bologna is to normalize, harmonize and standardize the teaching of medicine in European medical schools by implementing a similar curriculum. This objective assumes the presence of Urology as a university discipline in all European medical schools. At the same time, the teaching techniques and subject distributions have been modified, emphasizing practical teaching and active participation of the student in the acquisition of expertise and skills. This approach enhances the curricular presence of Urology and requires increased dedication from the teaching staff. These staff members, with limited face-to-face and classroom time, must inform and educate medical students on the broad healthcare commitment of urology as a surgical/medical specialty. The adaptation of the numerous European medical schools to the Bologna Plan raises a number of problems that can be easily overcome, as can be seen in the plan designed by the Faculty of Medicine at the Universidad Autonoma de Madrid.

Salud ósea en pacientes con cáncer de próstata / Bone health in patients with prostate cancer

Contexto: La salud ósea se ve comprometida en los pacientes con cáncer de próstata por la avanzada edad media al diagnóstico, los tratamientos de supresión androgénica y el desarrollo de metástasis óseas. Revisamos la literatura con la finalidad de actualizar el estado del arte sobre su incidencia, prevención y manejo. Adquisición de la evidencia: Realizamos una revisión de la literatura sobre afectación ósea en los pacientes con cáncer de próstata en diferentes contextos clínicos. Síntesis de la evidencia: Los pacientes diagnosticados de cáncer de próstata experimentan una disminución de la densidad mineral ósea mayor que varones de la misma edad antes de iniciar el tratamiento. La supresión androgénica provoca una pérdida de masa ósea más intensa durante el primer año de tratamiento, y parece ralentizarse a partir de entonces, persistiendo a largo plazo. Conocer del punto de partida y de la dinámica de la pérdida de masa ósea es importante para prevenir su progresión. Los eventos relacionados con el esqueleto ejercen gran impacto en la calidad de vida de los pacientes, y tanto el denosumab como el ácido zoledrónico han demostrado ser eficaces en su reducción. Conclusiones: La prevención y el manejo de la afectación ósea en pacientes con cáncer de próstata es determinante para su calidad de vida y exige un abordaje individualizado. Antes de iniciar una supresión androgénica prolongada debe valorarse la situación de riesgo basal del hueso para adoptar las medidas protectoras apropiadas. En aquellos con metástasis debe considerarse precozmente el inicio de terapias que disminuyan el riesgo de eventos óseo

Context: In patients with prostate cancer, bone health is compromised by advanced age at diagnosis, androgen suppression treatments and the developmentofbone metastases. In this paper the medical literature is reviewed in order to update the state of the art on their incidence, prevention and management. Evidence acquisition: A literature review about bone involvement in patients with prostate cancer in different clinical settings is performed. Synthesis of the evidence: Decreased bone mineral density is higher in patients diagnosed of prostate cancer before starting treatment than in healthy men with the same age. During the first year of treatment, a severe loss bone density is reported due to androgen suppression therapy. From then on, loss bone density seems to slow down, persisting at long-term. It is important to know the starting point and the dynamics of loss bone in order to prevent its progression. The skeletal events have an important impact on quality of life in patients with prostate cancer. Both Denosumab and Zoledronic Acid have proven effective in reducing loss bone. Conclusions: The prevention and management of bone involvement in patients with prostate cancer is critical to quality of life in these patients and requires an individualized approach. Before starting a prolonged androgen deprivation, baseline risk of fracture should be evaluated in order to adopt the proper protective measures. In patients with metastases, early treatments reducing the risk of bone events should be taken into account

Bone health in patients with prostate cancer.

CONTEXT: In patients with prostate cancer, bone health is compromised by advanced age at diagnosis, androgen suppression treatments and the developmentofbone metastases. In this paper the medical literature is reviewed in order to update the state of the art on their incidence, prevention and management. EVIDENCE ACQUISITION: A literature review about bone involvement in patients with prostate cancer in different clinical settings is performed. SYNTHESIS OF THE EVIDENCE: Decreased bone mineral density is higher in patients diagnosed of prostate cancer before starting treatment than in healthy men with the same age. During the first year of treatment, a severe loss bone density is reported due to androgen suppression therapy. From then on, loss bone density seems to slow down, persisting at long-term. It is important to know the starting point and the dynamics of loss bone in order to prevent its progression. The skeletal events have an important impact on quality of life in patients with prostate cancer. Both Denosumab and Zoledronic Acid have proven effective in reducing loss bone. CONCLUSIONS: The prevention and management of bone involvement in patients with prostate cancer is critical to quality of life in these patients and requires an individualized approach. Before starting a prolonged androgen deprivation, baseline risk of fracture should be evaluated in order to adopt the proper protective measures. In patients with metastases, early treatments reducing the risk of bone events should be taken into account.

Can benign prostatic hyperplasia be identified in the primary care setting using only simple tests? Results of the Diagnosis IMprovement in PrimAry Care Trial.

AIMS: Diagnosis IMprovement in PrimAry Care Trial (D-IMPACT) was a prospective, multicentre epidemiological study in three European countries to identify the optimal subset of simple tests applied in primary care to diagnose benign prostatic hyperplasia (BPH) in men who spontaneously present with lower urinary tract symptoms (LUTS). METHODS: Consecutive male patients aged ≥ 50 years who spontaneously attended their regular general practitioner (GP) office with LUTS were eligible for inclusion if they had not previously undergone BPH diagnostic tests or received treatment for BPH. Patients were assessed on three occasions, twice by their regular GP (visits 1 and 2) and once by a urologist (visit 3). The diagnostic accuracy of each variable was determined using the urologists' final BPH diagnosis (at visit 3) as gold-standard. Independent variables analysed were as follows: age; BPH diagnosis performed by GP in visit 1 (yes/no); probability of BPH diagnosis assessed by GP in visit 1; urinalysis (normal/abnormal); prostate-specific antigen (PSA); International Prostate Symptom Score (IPSS); diagnosis of BPH performed by GP in visit 2 (yes/no); and probability of BPH diagnosis assessed by GP in visit 2. Statistically significant variables (p < 0.1) were included in a logistic regression model to identify the best algorithm and describe each test contribution. RESULTS: The most frequent spontaneously reported LUTS were nocturia and weak urinary stream. BPH study prevalence was 66.0% (95%CI: 62.3-69.5) and 32% of patients were at risk of BPH progression (PSA > 1.5 ng/ml and prostate volume ≥ 30 cm(3)). Among the independent variables analysed, only age, IPSS and PSA showed a statistically significant relationship with BPH diagnosis. In a logistic regression model including age, IPSS, PSA and probability of BPH (based on physical examination and symptoms), positive predictive value (PPV) was 77.1%. Exclusion of BPH probability resulted in a PPV of 75.7%. CONCLUSIONS: A diagnostic algorithm including only objective variables (age, IPSS and PSA), easily implemented in any GP office, allows GPs to accurately diagnose BPH in approximately three-quarters of patients spontaneously reporting LUTS.

Cambios morfométricos peneanos tras prostatectomía radical: revisión de la evidencia / Penile morphometric changes after radical prostatectomy: Evidence-based

Introducción: La prostatectomía radical en cualquiera de sus abordajes representa el tratamiento de elección del cáncer localizado de la próstata y especialmente en pacientes jóvenes sexualmente activos con deseo de mantener su vida sexual. Además de la bien conocida y definida disfunción eréctil postoperatoria, el período de silencio eréctil causa en muchos pacientes (9–71%) cambios estructurales, a veces irreversibles, en la estructura peneana. Estos cambios tisulares derivan en una pérdida de longitud y grosor del pene, que preocupa a los pacientes. Objetivo: Revisar de manera sistemática los datos publicados en la literatura médica hasta el momento en relación con los cambios peneanos tras prostatectomía radical. Material y métodos: Realizamos una búsqueda sistemática en PubMed, EMBASE, Cochrane, SCOPUS y Science Citation Index durante el período de enero de 1990 a septiembre de 2009 para los términos «prostatectomy», «organ size», «fibrosis», «sexual activity», «erectile dysfunction», «penile size», «radical prostatectomy», «prostatic neoplasms», «body weights» y «penis measures».Material y métodosSe seleccionaron 7 series de pacientes para su análisis. Resultados: Se exponen los diferentes métodos de medición peneana y sus potenciales sesgos y diferencias. Asimismo, repasamos las principales teorías fisiopatogénicas para explicar este fenómeno. Finalmente, se detallan los resultados de diferentes series de pacientes comunicadas. Conclusiones: Parece un hecho demostrado que el pene sufre cambios importantes en su longitud y grosor tras prostatectomía radical. Diferentes autores han comunicado los datos de sus series así como las diferentes opciones de tratamiento (inhibidores de la 5-PDE, dispositivos de vacío [DV], extensores del pene, etc.). Las estrategias encaminadas a preservar y a proteger el tejido cavernoso y la túnica albugínea tras el procedimiento así como las que aumenten la oxigenación y permitan recuperar la erección en el menor tiempo posible impactarán positivamente en la calidad de nuestros pacientes (AU)

Introduction: Radical prostatectomy in all its approaches is the treatment of choice for localized prostate cancer and especially in young, sexually active patients with a desire to keep their sex life. In addition to the well-known and defined postoperative erectile dysfunction, erectile silent period causes, in many patients (9–1%), structural changes, in the penile structure, sometimes irreversible. These tissue changes, resulting in a loss of length and girth, that concern patients. Objective: To systematically review to date published data in the literature regarding penile changes after radical prostatectomy. Material and methods: We performed a systematic search in: PubMed, EMBASE, Cochrane, SCOPUS, Science Citation Index period January 1990 to September 2009 for the terms “prostatectomy”, “organ size”, “fibrosis”, “sexual activity”, “erectile dysfunction”, “penile size”, “radical prostatectomy”, “prostatic neoplasms”, “body weights” and “penis measures”. Seven series of patients were selected for analysis. Results: We described the different measurement methods and their potential biases and differences. Also, we reviewed main physiopathogenic theories to explain this phenomenon. Finally, we detail the results of different series of patients reported. Conclusions: It seems to be a proven fact that the penis undergoes major changes in its length and girth after radical prostatectomy. Several authors have communicated the data of their series and the different treatment options (5PDE inhibitors, vacuum devices, penile extenders, etc.). Strategies addressed to preserve and protect cavernous tissue and tunica albuginea after the procedure, as well as to increase oxygenation and allow erection to be recovered in the shortest posible time positive will impact on the quality of life of our patients (AU)

[Penile morphometric changes after radical prostatectomy: Evidence-based]. / Cambios morfométricos peneanos tras prostatectomía radical: revisión de la evidencia.

INTRODUCTION: Radical prostatectomy in all its approaches is the treatment of choice for localized prostate cancer and especially in young, sexually active patients with a desire to keep their sex life. In addition to the well-known and defined postoperative erectile dysfunction, erectile silent period causes, in many patients (9-1%), structural changes, in the penile structure, sometimes irreversible. These tissue changes, resulting in a loss of length and girth, that concern patients. OBJECTIVE: To systematically review to date published data in the literature regarding penile changes after radical prostatectomy. MATERIAL AND METHODS: We performed a systematic search in: PubMed, EMBASE, Cochrane, SCOPUS, Science Citation Index period January 1990 to September 2009 for the terms prostatectomy, organ size, fibrosis, sexual activity, erectile dysfunction, penile size, radical prostatectomy, prostatic neoplasms, body weights and penis measures. Seven series of patients were selected for analysis. RESULTS: We described the different measurement methods and their potential biases and differences. Also, we reviewed main physiopathogenic theories to explain this phenomenon. Finally, we detail the results of different series of patients reported. CONCLUSIONS: It seems to be a proven fact that the penis undergoes major changes in its length and girth after radical prostatectomy. Several authors have communicated the data of their series and the different treatment options (5PDE inhibitors, vacuum devices, penile extenders, etc.). Strategies addressed to preserve and protect cavernous tissue and tunica albuginea after the procedure, as well as to increase oxygenation and allow erection to be recovered in the shortest possible time positive will impact on the quality of life of our patients.

Can simple tests performed in the primary care setting provide accurate and efficient diagnosis of benign prostatic hyperplasia? Rationale and design of the Diagnosis Improvement in Primary Care Trial.

Effective treatment of benign prostatic hyperplasia (BPH) improves lower urinary tract symptoms (LUTS) and patient quality of life, and reduces the risk of complications arising from disease progression. However, treatment can only be initiated when men with BPH are identified by accurate diagnostic tests. Current evidence suggests that diagnostic procedures employed by primary care physicians vary widely across Europe. The expected increases in BPH prevalence accompanying the gradual aging of the population, coupled with greater use of medical therapy, mean that general practitioners (GPs) are likely to have an increasingly important role in managing the condition. The GP/primary care clinic is therefore an attractive target location for strategies designed to improve the accuracy of BPH diagnosis. The Diagnosis Improvement in Primary Care Trial (D-IMPACT) is a prospective, multicentre, epidemiological study that aims to identify the optimal subset of simple tests applied by GPs in the primary care setting to diagnose BPH in men who spontaneously report obstructive (voiding) and/or irritative (storage) LUTS. These tests comprise medical history, symptom assessment with the International Prostate Symptom Score questionnaire, urinalysis, measurement of serum levels of prostate-specific antigen and subjective GP diagnosis after completing all tests including digital rectal examination. GP diagnoses and all other tests will be compared with gold-standard diagnoses provided by specialist urologists following completion of additional diagnostic tests. D-IMPACT will establish the diagnostic performance using a non-subjective and reproducible algorithm. An adjusted and multivariate analysis of the results of D-IMPACT will allow identification of the most efficient combination of tests that facilitate accurate BPH diagnosis in the primary care setting. In addition, D-IMPACT will estimate the prevalence of BPH in patients who present spontaneously to GPs with LUTS.

CCL18 is expressed in patients with bullous pemphigoid and parallels disease course.

BACKGROUND: The autoimmune skin disease bullous pemphigoid (BP) is characterized by subepidermal blister formation and a strong dermal infiltrate of mononuclear cells and eosinophils as well as a T-helper (Th) 2-dominated cytokine milieu. CCL18 is a chemokine, with unknown receptor counterpart, frequently associated with inflammatory Th2-type responses. OBJECTIVES: The study was performed to investigate an association of CCL18 with BP. METHODS: CCL18 was determined by enzyme-linked immunosorbent assay in serum and blister fluid of patients with BP, pemphigus vulgaris and healthy individuals. In vitro chemotaxis assays were performed to demonstrate migration of peripheral blood mononuclear cells to BP blister fluid. Immunohistology and immunofluorescence staining were used to evaluate CCL18 expression in skin. RESULTS: We have found that the levels of CCL18 in sera from patients with BP are 84% higher than those normally observed in healthy individuals. In addition, blister fluid of patients with BP is extremely rich in CCL18, reaching concentrations which are fivefold and sevenfold higher than those found in the sera of patients with BP and healthy individuals, respectively. Using immunofluorescence techniques we identified Langerhans cells, antigen-presenting cells of the dermis and eosinophils as producers of CCL18 in BP skin. We studied the possibility of using CCL18 expression as a biomarker linked to BP by monitoring the serum levels of CCL18 and the disease course of nine patients with BP over a maximum period of 54 months. In this study, CCL18 levels correlated with the disease course in most of the patients. CONCLUSIONS: Our data implicate CCL18 as a functionally relevant chemokine in BP, mediating recruitment of blood mononuclear cells into the hallmark infiltrated skin lesion. The high correlation of CCL18 expression and BP disease suggests that blood levels of this chemokine can be used as an easy method to monitor disease progression and/or efficacy of therapeutic interventions.

[Economic evaluation of medical treatment of benign prostatic hyperplasia (BPH) in the specialised care setting in Spain. Application to the cost-effectiveness of two drugs frequently used in its treatment]. / Evaluación económica del tratamiento médico de la hiperplasia benigna de próstata (HBP) en España en atención especializada. Aplicación al coste- efectividad de dos fármacos habitualmente utilizados en su tratamiento.

OBJECTIVES: To develop a pharmacoeconomic study in order to know the average cost of BPH diagnosis and follow-up in Spain in the Urology Department setting from the perspective of the public health system, considering two frequently used drugs in the Spanish Healthcare environment, an alpha-blocker (tamsulosin) and the lipido-sterolic extract of Serenoa repens (Permixon). MATERIAL AND METHODS: Direct healthcare costs of BPH diagnosis and treatment were determined for each clinical stage according to the International Prostate Symptom Score (IPSS): mild, moderate and severe. Data on the usage and unit costs of healthcare resources were obtained from a semi-structured interview with clinical experts. The clinical efficacy of the medical treatments was obtained from the PERMAL clinical study, where therapeutic equivalence between the two studied drugs was observed. RESULTS: For patients treated in the Urology Department setting, the average annual cost of diagnostic tests and medical visits related to mild, moderate or severe BPH symptoms were, respectively, Euro 124, Euro 207, and Euro 286. The average annual cost of the drugs, including adverse effects treatment, was Euro 211 for Permixon and Euro 346 for tamsulosin. DISCUSSION: Costs of medical care of BPH increases with symptom intensity. Pharmacological treatment makes up a significant part of the disease's cost. According to the model used, treatment with Permixon is considerably more cost-effective than with tamsulosin, offering average yearly savings of Euro 135 per patient.

Evaluación económica del tratamiento médico de la hiperplasia benigna de próstata (HBP) en España en atención especializada. Aplicación al coste-efectividad de dos fármacos habitualmente utilizados en su tratamiento / Economic evaluation of medical treatment of benign prostatic hyperplasia (BPH) in the specialised care setting in Spain. Application to the cost-effectiveness of two drugs frequently used in its treatment

Objetivos: Llevar a cabo un estudio fármaco económico para conocer el coste medio del diagnóstico y seguimiento de la HBP en España en el ámbito de la atención especializada desde la perspectiva del sistema público de salud, considerando dos fármacos frecuentemente utilizados en el entorno sanitario español, un alfabloqueante (tamsulosina) y el extracto lipido esterólico de Serenoa repens (Permixón(R)).Material y métodos: Se determinaron los costes sanitarios directos del diagnóstico y tratamiento de la HBP para cada presentación clínica según el valor del International Prostate Symptom Score (IPSS): leve, moderada y grave. Los datos sobre el consumo y los costes unitarios de los recursos sanitarios se recogieron mediante una encuesta semi-estructurada a expertos clínicos. La eficacia clínica del tratamiento médico fue obtenida del estudio clínico PERMAL, en el que se observó equivalencia terapéutica entre ambos fármacos. Resultados: El coste medio anual de pruebas diagnósticas y visitas médicas de la HBP sintomática según fuese leve, moderada o grave fueron, respectivamente, 124 €, 207€ y 286€ para pacientes tratados en atención especializada. El coste medio anual del tratamiento médico, incluyendo la atención de los efectos adversos fue de 211€ para Permixón(R) y 346 € paratamsulosina. Discusión: El coste de la atención médica de la HBP es proporcional a la intensidad de la sintomatología. El tratamiento farmacológico constituye una parte significativa del coste de la enfermedad. En base al modelo utilizado, el tratamiento con Permixón(R) es sensiblemente más coste-efectivo que el tratamiento con tamsulosina, representando un ahorro medio de 135€ por paciente y año (AU)

Objectives: To develop a pharmaco economic study in order to know the average cost of BPH diagnosis and follow-up in Spain in the Urology Department setting from the perspective of the public health system, considering two frequently used drugs in the Spanish Healthcare environment, an alpha-blocker (tamsulosin) and the lipido-sterolic extract of Serenoa repens (Permixon(R)).Material and methods: Direct healthcare costs of BPH diagnosis and treatment were determined for each clinical stage according to the International Prostate Symptom Score (IPSS): mild, moderate and severe. Data on the usage and unit costs of healthcare resources were obtained from a semi-structured interview with clinical experts. The clinical efficacy of the medical treatments was obtained from the PERMAL clinical study, where therapeutic equivalence between the two studied drugs was observed. Results: For patients treated in the Urology Department setting, the average annual cost of diagnostic tests and medical visits related to mild, moderate or severe BPH symptoms were, respectively, € 124, € 207, and € 286. The average annual cost of the drugs, including adverse effects treatment, was € 211 for Permixon(R) and € 346 for tamsulosin. Discussion: Costs of medical care of BPH increases with symptom intensity. Pharmacological treatment makes up a significant part of the disease’s cost. According to the model used, treatment with Permixon(R) is considerably more cost-effective than with tamsulosin, offering average yearly savings of € 135 per patient (AU)