Showing papers by "Javier C. Angulo published in 2016"

Diabetes and ageing‐induced vascular inflammation

Abstract: Diabetes and the ageing process independently increase the risk for cardiovascular disease (CVD). Since incidence of diabetes increases as people get older, the diabetic older adults represent the largest population of diabetic subjects. This group of patients would potentially be threatened by the development of CVD related to both ageing and diabetes. The relationship between CVD, ageing and diabetes is explained by the negative impact of these conditions on vascular function. Functional and clinical evidence supports the role of vascular inflammation induced by the ageing process and by diabetes in vascular impairment and CVD. Inflammatory mechanisms in both aged and diabetic vasculature include pro-inflammatory cytokines, vascular hyperactivation of nuclear factor-кB, increased expression of cyclooxygenase and inducible nitric oxide synthase, imbalanced expression of pro/anti-inflammatory microRNAs, and dysfunctional stress-response systems (sirtuins, Nrf2). In contrast, there are scarce data regarding the interaction of these mechanisms when ageing and diabetes co-exist and its impact on vascular function. Older diabetic animals and humans display higher vascular impairment and CVD risk than those either aged or diabetic, suggesting that chronic low-grade inflammation in ageing creates a vascular environment favouring the mechanisms of vascular damage driven by diabetes. Further research is needed to determine the specific inflammatory mechanisms responsible for exacerbated vascular impairment in older diabetic subjects in order to design effective therapeutic interventions to minimize the impact of vascular inflammation. This would help to prevent or delay CVD and the specific clinical manifestations (cognitive decline, frailty and disability) promoted by diabetes-induced vascular impairment in the elderly.

Asymmetric dimethylarginine (ADMA) elevation and arginase up-regulation contribute to endothelial dysfunction related to insulin resistance in rats and morbidly obese humans

Abstract: Key points The presence of insulin resistance (IR) is determinant for endothelial dysfunction associated with obesity. Although recent studies have implicated the involvement of mitochondrial superoxide and inflammation in the defective nitric oxide (NO)-mediated responses and subsequent endothelial dysfunction in IR, other mechanisms could compromise this pathway. In the present study, we assessed the role of asymmetric dimethylarginine (ADMA) and arginase with respect to IR-induced impairment of endothelium-dependent vasodilatation in human morbid obesity and in a non-obese rat model of IR. We show that both increased ADMA and up-regulated arginase are determinant factors in the alteration of the l-arginine/NO pathway associated with IR in both models and also that acute treatment of arteries with arginase inhibitor or with l-arginine significantly alleviate endothelial dysfunction. These results help to expand our knowledge regarding the mechanisms of endothelial dysfunction that are related to obesity and IR and establish potential therapeutic targets for intervention. Abstract Insulin resistance (IR) is determinant for endothelial dysfunction in human obesity. Although we have previously reported the involvement of mitochondrial superoxide and inflammation, other mechanisms could compromise NO-mediated responses in IR. We evaluated the role of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) and arginase with respect to IR-induced impairment of l-arginine/NO-mediated vasodilatation in human morbid obesity and in a non-obese rat model of IR. Bradykinin-induced vasodilatation was evaluated in microarteries derived from insulin-resistant morbidly obese (IR-MO) and non-insulin-resistant MO (NIR-MO) subjects. Defective endothelial vasodilatation in IR-MO was improved by l-arginine supplementation. Increased levels of ADMA were detected in serum and adipose tissue from IR-MO. Serum ADMA positively correlated with IR score and negatively with pD2 for bradykinin. Gene expression determination by RT-PCR revealed not only the decreased expression of ADMA degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH)1/2 in IR-MO microarteries, but also increased expression of arginase-2. Arginase inhibition improved endothelial vasodilatation in IR-MO. Analysis of endothelial vasodilatation in a non-obese IR model (fructose-fed rat) confirmed an elevation of circulating and aortic ADMA concentrations, as well as reduced DDAH aortic content and increased aortic arginase activity in IR. Improvement of endothelial vasodilatation in IR rats by l-arginine supplementation and arginase inhibition provided functional corroboration. These results demonstrate that increased ADMA and up-regulated arginase contribute to endothelial dysfunction as determined by the presence of IR in human obesity, most probably by compromising arginine availability. The results provide novel insights regarding the mechanisms of endothelial dysfunction related to obesity and IR and establish potential therapeutic targets for intervention.

The Expression of Fibroblast Activation Protein in Clear Cell Renal Cell Carcinomas Is Associated with Synchronous Lymph Node Metastases.

Abstract: Clear cell renal cell carcinoma (CCRCC) is a heterogeneous and complex disease that frequently develops distant metastases. Fibroblast activation protein (FAP) is a serine peptidase the expression of which in cancer-associated fibroblasts has been associated with higher risk of metastases and poor survival. The objective of this study was to evaluate the role of FAP in metastatic CCRCC (mCCRCC). A series of 59 mCCRCC retrospectively collected was included in the study. Metastases developed either synchronous (n = 14) or metachronous to renal disease (n = 45). Tumor specimens were obtained from both primary lesion (n = 59) and metastases (n = 54) and FAP expression was immunohistochemically analyzed. FAP expression in fibroblasts from primary tumors correlated with FAP expression in the corresponding metastatic lesions. Also, primary and metastatic FAP expression was correlated with large tumor diameter (>7cm), high grade (G3/4), high stage (pT3/4), tumor necrosis and sarcomatoid transformation. The expression of FAP in primary tumors and in their metastases was associated both with synchronous metastases and also with metastases to the lymph nodes. FAP expression in the primary tumor was correlated with worse 10-year overall survival. Immunohistochemical detection of FAP in the stromal tumor fibroblasts could be a biomarker of early lymph node metastatic status and therefore could account for the poor prognosis of FAP positive CCRCC.

A systematic review and meta-analysis on the efficacy of intravesical therapy for bladder pain syndrome/interstitial cystitis.

Abstract: Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic disease characterised by persistent irritating micturition symptoms and pain. The objective was to compare the clinical efficacy of currently available products for intravesical therapy of BPS/IC and to assess their pharmacoeconomic impact. A Pubmed/Medline database search was performed for articles on intravesical therapy for BPS/IC. A total of 345 publications were identified, from which 326 were excluded. Statistical evaluation was performed with effect size (ES) assessment of symptom reduction and response rates. The final set of 19 articles on intravesical BPS/IC therapy included 5 prospective controlled trials (CTs), the remaining were classified as uncontrolled clinical studies. The total number of patients included was 801, 228 of whom had been evaluated in a CT. For CTs, the largest ES for symptom reduction as well as response rate was observed for high molecular weight hyaluronic acid (HMW-HA), with similar findings in two uncontrolled studies with HMW-HA. The number needed to treat to achieve a response to intravesical therapy was 2.67 for intravesical pentosan polysulphate and 1.31 for HMW-HA which were superior to all other instillates. HMW-HA was significantly superior in cost effectiveness and cost efficacy to all other instillation regimes. The present meta-analysis combined medical and pharmacoeconomic aspects and demonstrated an advantage of HMW-HA over other instillation agents; however, direct comparisons between the different products have not been performed to date in properly designed controlled studies.

Patient-reported outcomes with the β3 -adrenoceptor agonist mirabegron in a phase III trial in patients with overactive bladder

Abstract: Aims To assess patient-reported outcomes (PROs) in patients with overactive bladder (OAB) receiving the novel β3-adrenoceptor agonist mirabegron. Methods Data from a randomised, double-blind, controlled phase III trial in 1,987 patients aged ≥18 years with OAB symptoms for ≥3 months were analysed. Patients received placebo, mirabegron 50 or 100 mg/day, or tolterodine extended release (ER) 4 mg orally once daily for 12 weeks after a 2-week placebo run-in. Prespecified analysis of PROs (changes in OAB Questionnaire [OAB-q], Patient Perception of Bladder Condition [PPBC], and Work Productivity and Activity Impairment: Specific Health Problem [WPAI-SHP] instrument) in patients treated with mirabegron 50 mg/day, tolterodine ER 4 mg/day or placebo is reported. Post-hoc analyses of OAB-q, PPBC and the Treatment Satisfaction-Visual Analogue Scale (TS-VAS) in patients who were incontinent at baseline are also reported. Results Significant improvements over placebo in OAB-q coping and concern from baseline to final visit were observed with mirabegron 50 mg/day. No significant improvements in these parameters were observed with tolterodine ER 4 mg/day. Mirabegron 50 mg/day significantly increased the proportion of patients showing a PPBC improvement over placebo. Mirabegron 50 mg/day also produced greater improvements in WPAI-SHP presenteeism and greater reductions in absenteeism and overall work impairment than placebo or tolterodine ER 4 mg/day. The impact of mirabegron 50 mg/day treatment on PROs in the incontinent population appears to be greater than that in the overall OAB population. Conclusions At the approved dose of 50 mg/day, mirabegron significantly improves OAB patients' perception of disease and quality of life, independent of whether they are incontinent at baseline. Neurourol. Urodynam. 35:987–994, 2016. © 2015 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc.

Estudio retrospectivo de diferentes opciones de tratamiento conservador con Bacilo de Calmette-Guèrin en el carcinoma urotelial vesical T1G3: terapia de mantenimiento

Abstract: Resumen Objetivo Comparar diferentes opciones de tratamiento conservador del tumor vesical no musculo-invasivo (TVNMI) T1 de grado alto. El bacilo de Calmette-Guerin (BCG) es el tratamiento intravesical preferido para los tumores T1 de grado alto; sin embargo, algunos expertos aun cuestionan la necesidad de la BCG de mantenimiento. Materiales y metodos Se analizaron retrospectivamente los datos de 1.039 pacientes con TVNMI T1G3 primario y recurrente. Todos los pacientes fueron tratados mediante una reseccion transuretral del tumor vesical (RTUTV) completa, con musculo en la muestra y multiples biopsias de la vejiga. Los pacientes fueron tratados con solo una RTUTV inicial (n = 108), re-RTUTV (n = 153), induccion con 27 mg de BCG (cepa Connaught) (n = 87), induccion con 81 mg de BCG (n = 489) o induccion con 81 mg de BCG + mantenimiento (n = 202). El tiempo hasta la primera recidiva, progresion (a T2 o mayor, o a enfermedad metastasica) y mortalidad especifica de la enfermedad se evaluaron mediante la funcion de supervivencia de Kaplan-Meier y se compararon utilizando la prueba de logaritmo del rango (log-rank) y el modelo multivariado de regresion de Cox de riesgos proporcionales. Resultados El seguimiento medio fue de 62 ± 39 meses. El riesgo de recurrencia fue significativamente menor en los pacientes tratados con terapia de mantenimiento con 81 mg de BCG que en los otros grupos de tratamiento (p Conclusiones En el caso del TVNMI T1G3, la dosis completa de BCG con mantenimiento va asociada a mejores resultados de recurrencia que otras modalidades de tratamiento conservador. Los resultados de progresion y de supervivencia especifica de la enfermedad tambien fueron mejores con la BCG de induccion, con o sin mantenimiento.

Retrospective study of various conservative treatment options with bacille Calmette-Guérin in bladder urothelial carcinoma T1G3: Maintenance therapy.

Abstract: Objective To compare various conservative treatment options for high-grade T1 nonmuscle-invasive bladder cancer (NMIBC). Bacille Calmette-Guerin (BCG) is the preferred intravesical treatment for high-grade T1 tumors; however, a number of experts still question the need for maintenance BCG. Material and methods We retrospectively analyzed data from 1039 patients with primary and recurrent T1G3 NMIBC. All patients underwent complete transurethral resection of the bladder tumor (TURBT), with muscle in the sample and multiple bladder biopsies. The patients were treated with the following: only one initial TURBT (n = 108), re-TURBT (n = 153), induction with 27 mg of BCG (Connaught strain) (n = 87), induction with 81 mg of BCG (n = 489) or induction with 81 mg of BCG + maintenance (n = 202). The time to first recurrence, progression (to T2 or greater or to metastatic disease) and specific mortality of the disease was assessed using the Kaplan–Meier survival function and were compared using the log-rank test and the Cox multivariate regression model of proportional risks. Results The mean follow-up was 62 ± 39 months. The risk of recurrence was significantly lower for the patients treated with maintenance therapy of 81 mg of BCG than in the other treatment groups (p < 0.001). The risk of tumor progression was also significantly lower for the patients treated with maintenance BCG than for the patients treated only with one TURBT, re-TURBT and with induction therapy with 27 mg of BCG (p = 0.0003). The specific disease mortality was significantly lower with BCG maintenance (9.4%) than with only one TURBT (27.8%; p = 0.003). Conclusions In the case of T1G3 NMIBC, a complete dose of BCG with maintenance is associated with better recurrence results than are other conservative treatment modalities. The results of progression and survival specific to the disease were also better with induction BCG, with or without maintenance.

DNA Methylation and Urological Cancer, a Step Towards Personalized Medicine: Current and Future Prospects

Abstract: Urologic malignancies are some of the commonest tumors often curable when diagnosed at early stage. However, accurate diagnostic markers and faithful predictors of prognosis are needed to avoid over-diagnosis leading to overtreatment. Many promising exploratory studies have identified epigenetic markers in urinary malignancies based on DNA methylation, histone modification and non-coding ribonucleic acid (ncRNA) expression that epigenetically regulate gene expression. We review and discuss the current state of development and the future potential of epigenetic biomarkers for more accurate and less invasive detection of urological cancer, tumor recurrence and progression of disease serving to establish diagnosis and monitor treatment efficacies. The specific clinical implications of such methylation tests on therapeutic decisions and patient outcome and current limitations are also discussed.

Impacto del número de episodios diarios de incontinencia de urgencia en los resultados descritos por el paciente con vejiga hiperactiva

Abstract: Resumen Objetivo Explorar el impacto de la incontinencia urinaria de urgencia (IUU) en el bienestar de los pacientes no institucionalizados con vejiga hiperactiva (VH) en una muestra de la comunidad. Metodos Se llevo a cabo un estudio transversal basado en Internet en la poblacion general, incluyendo hombres y mujeres, >18 anos de edad. Los pacientes con probable VH se identificaron utilizando un algoritmo validado junto con una puntuacion ≥8 en la escala OAB-V8. La presencia de comportamiento de adaptacion se considero determinante para el diagnostico clinico de la VH. Se determino bienestar individual a traves de una bateria de mediciones de resultados comunicados por el paciente (PRO) incluida la evaluacion de la calidad de vida relacionada con la salud (EQ-5D), alteraciones del sueno (sueno MOS) y satisfaccion con la vida (LISAT-8). Los pacientes fueron agrupados de acuerdo con el numero de episodios diarios de IUU (gravedad IUU): 0 (VH seca), 1, 2-3 o ≥4. Se realizo un analisis multivariado para evaluar los factores que afectan de forma independiente la calidad de vida. Resultados Un total de 396 pacientes (52,5% mujeres, media de edad: 55,3 [11,1] anos, OAB-V8 puntuacion media: 14,5 [7,9]) de 2.035 sujetos participantes de la poblacion general cumplieron los criterios de VH: 203 (51,3%) con 0 episodios; 119 (30,1%) con 1; 52 (13,1%) con 2 o 3 y 22 (5,6%) con >4 episodios. Se encontro una asociacion ajustada lineal estadisticamente significativa entre el numero de episodios de IUU y las puntuaciones de PRO. Los participantes con mas episodios tenian peores perfiles de salud y calidad de autoevaluacion de la vida, peor satisfaccion con la vida, mas trastornos del sueno y menos horas de sueno por noche. El numero de episodios de incontinencia fue factor independiente para afectar a la calidad de vida utilizando los cuestionarios LISAT-8 y MOS. Conclusion La gravedad de la IUU se asocio significativamente con peor bienestar individual en los sujetos con VH en una muestra comunitaria en Espana.

Impact of daily number of urgency urinary incontinence episodes on overactive bladder patient reported outcomes

Abstract: Objective To explore the impact of urgency urinary incontinence (UUI) on well-being in non-institutionalized patients with overactive bladder (OAB) in a community sample. Methods A cross-sectional web-based study was conducted in the general population, including males and females, >18 years of age. Patients with probable OAB were identified using a validated algorithm together with a score ≥8 on the OAB-V8 scale. Presence of coping behavior was considered determinant for the clinical diagnosis of OAB. Individual well-being was determined through a battery of patient-reported outcomes (PRO) measurements including assessment of health-related quality of life (EQ-5D), sleep disturbances (MOS Sleep), and life satisfaction (LISAT-8). Patients were grouped according to the number of daily UUI episodes (UUI severity): 0 (dry OAB), 1, 2–3, or ≥4. Multivariate analysis to evaluate factors independently affecting quality of life was undertaken. Results A total of 396 patients (52.5% women, mean age: 55.3 [11.1] years, OAB-V8 mean score: 14.5 [7.9]) out of 2035 subjects participating from the general population met the criteria for OAB: 203 (51.3%) with 0 episodes, 119 (30.1%) with 1, 52 (13.1%) with 2 or 3, and 22 (5.6%) with ≥4 episodes. A statistically significant linear adjusted association was found between number of UUI episodes and PRO scores. Participants with more episodes had poorer health profiles and self-evaluated quality of life, worse life satisfaction, and more sleep disturbances and fewer hours of sleep per night. Number of incontinence episodes was independent factor to affect quality of life using both LISAT-8 and MOS questionnaires. Conclusion Severity of UUI was significantly associated with poorer individual well-being in subjects with OAB in a community sample in Spain.

A DNA Hypermethylation Profile Independently Predicts Biochemical Recurrence Following Radical Prostatectomy

Abstract: Purpose: Detection of DNA hypermethylation is emerging as a novel molecular biomarker for different malignancies. We intend to define whether a hypermethylation p

Cost effectiveness analysis of fesoterodine compared to mirabegron in first-line therapy setting for overactive bladder with urge urinary incontinence, from the Spanish National Health System perspective.

Abstract: Objectives To evaluate the cost–effectiveness of first-line treatment of Overactive Bladder (OAB) with fesoterodine relative to mirabegron, from the Spanish National Health System (NHS) perspective. Methods A decision tree model was developed to represent a typical clinical process of 52-week of treatment for an OAB patient with urge urinary incontinence (UUI) initiating first-line therapy with fesoterodine 4 mg, including optional titration to 8 mg, vs.mirabegron 50 mg. Efficacy data were obtained from a Bayesian indirect treatment meta-analysis. Patients with UUI of less than one episode/day were defined as treatment responder and persistence was assessed at weeks 4, 12 and 24. At week 12, non-responders discontinued treatment permanently. Quality-adjusted life years (QALYs) were calculated based on time spent in responder and non-responder states. OAB-related drug and medical care costs including physician visits, laboratory tests, incontinence pads, and comorbidities (fracture, skin infection, urinary tract infections and depression) were modeled and expressed in €2015. Results At week 52, the percentage of responders was 20.8% for patients starting on fesoterodine 4 mg who optionally titrated to 8 mg and 19.4% for patients treated with mirabegron. QALYs were slightly higher with fesoterodine than mirabegron (0.7703 vs. 0.7668, difference = 0.0035). Fesoterodine treatment also had slightly higher total costs than mirabegron (3296€ vs. 3217, difference = 79€), resulting in a cost of 22,523/QALY€ gained for fesoterodine versus mirabegron. Probabilistic sensitivity analysis confirmed the slight advantage of fesoterodine with a 61.1% probability of being cost-effective at the 30,000€ willingness-to-pay for 1 QALY threshold. Conclusions Given the relatively small 1-year cost difference between the two treatments, fesoterodine can be considered a cost-effective option relative to mirabegron for the first-line management of OAB with UUI in Spain.

Two-Port Laparoscopic Reconstructive Surgery of the Urinary Tract with Reusable Umbilical System (Hybrid Less): A Proof of Concept Study.

Abstract: Objectives: We compared perioperative results and complications of reconstructive surgery of the urinary tract performed using a multichannel platform through the umbilicus and one additional 3.5-mm with a cohort of patients simultaneously treated with conventional 4-port laparoscopy. Materials and Methods: Matched-pair study comparing perioperative outcomes, postoperative visual analogue pain scale (VAPS) and morbidity of 2-port (n = 20) and 4-port (n = 10) laparoscopic reconstructive urological surgery. Preoperative and perioperative data compared included demographics, type of surgery, operative time, blood loss, decrease in serum hemoglobin, operative complications, length of stay and postoperative complications according to Clavien-Dindo classification. Results: There was no significant difference between groups regarding age, gender, body mass index, American Society of Anesthesiologists score, type of surgery, operative time, operative complications and intraoperative or postoperative transfusion. Estimated blood loss was lower using reduced-port approach. VAPS at postoperative day one was significantly lower for 2-port approach and so was the length of stay. Patient satisfaction with the wound was higher for 2-port surgery. Differences were not observed in number and severity of postoperative complications. Conclusions: Urological reconstructive operations can be safely performed using the hybrid laparoendoscopic single-site umbilical approach, resulting in lower blood loss, higher patient satisfaction and lower postoperative pain, which also facilitate earlier hospital discharge, than the same reconstructive procedures performed through multiport conventional laparoscopy.

Contaminación de antígeno específico-prostático a largo plazo en la rama española del Estudio Aleatorizado Europeo de Screening del Cáncer de Próstata (ERSPC)

Abstract: Resumen Objetivos Recientemente, el Estudio Aleatorizado Europeo de Screening del Cancer de Prostata consiguio una reduccion de la mortalidad por cancer de prostata mediante la determinacion serica de antigeno especifico-prostatico (PSA). Estos resultados no fueron reproducidos en la rama espanola del Estudio Aleatorizado Europeo de Screening del Cancer de Prostata. La contaminacion de PSA (determinacion oportunista fuera del estudio) podria disminuir el poder de contraste del estudio si se lleva a cabo en el brazo control. Hemos calculado la tasa de contaminacion de PSA a largo plazo, y su efecto en la realizacion de biopsia prostatica y en la deteccion de cancer. Material y metodos Se aleatorizaron 4.276 varones (2.415 brazo screening, 1.861 brazo control) en la seccion espanola del Estudio Aleatorizado Europeo de Screening del Cancer de Prostata. No se programo la determinacion de PSA en el brazo control. Se indico biopsia prostatica sextante si PSA ≥ 3 ng/ml. Toda determinacion de PSA realizada fuera del estudio fue etiquetada como «contaminacion de PSA». Se calcularon las tasas de contaminacion de PSA, realizacion de biopsia y deteccion de cancer. Resultados Las medianas de edad y tiempo de seguimiento fueron de 57 y 15,1 anos respectivamente. Un total de 2.511 varones se realizo al menos una determinacion de PSA fuera del estudio. La contaminacion de PSA a los 5, 10 y 15 anos fue del 22; 47,1 y 66,3% en el brazo screening, y del 20,8; 43,2 y 58,6 en el brazo control, respectivamente (p Conclusiones Aunque la contaminacion acumulada de PSA fue notable en los 2 brazos del estudio, la realizacion de biopsia prostatica fue escasa en el brazo control. Por ello, creemos que el impacto de la contaminacion de PSA sobre el poder estadistico del estudio debe ser limitado.

Survival predictors in patients with prostate adenocarcinoma with hormonal blockade.

Abstract: Ki-67 index and clinical-pathological factors such as the Gleason score and the presence of neuroendocrine differentiation have been used for predicting survival in patients with prostate cancer. We examined prostate tissue from 45 patients with advanced prostate cancer who were treated with maximal androgen blockade and analysed their cancer-specific survival (CSS). We assessed the Gleason index, performed an immunohistochemical analysis of Ki-67 (MIB-1) and determined the presence of neuroendocrine differentiation (chromogranin A). A survival study was conducted using Kaplan-Meier curves (log-rank test) and a Cox regression analysis. Twenty-four patients (53.3%) died from the disease, with a mean follow-up of 68.7±7.7 months (56.6% CSS at 5 years and 31.8% at 10 years). In the univariate analysis, survival was associated with an interquartile distribution of Ki-67 (0-5, 6-12%, 13-25%, >25%; log-rank, p=0.01), Gleason 5 (total index 9-10; log-rank, p=0.002) and the presence of metastases during the diagnosis (M1; log-rank, p=0.004) but not to cT category (T3-T4; log-rank, p=0.26) or neuroendocrine differentiation (immunohistochemically positive tumour cell nests; log-rank, p=0.46). The multivariate analysis revealed that a Ki-67 index ≤12% (HR, 0.22; p=0.0009) and the absence of metastases (M0) during diagnosis (HR, 0.17; p=0.0002) were protective factors in this population. In conclusion, Ki-67 proliferation index and the lack of metastases at diagnosis predict CSS in patients with advanced prostate cancer who undergo hormonal blockade. Neuroendocrine differentiation in tumour tissue had no prognostic value in this study.

Análisis de coste efectividad de fesoterodina comparado con mirabegron en el marco de tratamiento de primera línea para vejiga hiperactiva con incontinencia urinaria de urgencia, desde la perspectiva del Sistema Nacional de Salud español

Abstract: Resumen Objetivos Evaluar el coste-efectividad del tratamiento de primera linea de la vejiga hiperactiva (VH) con fesoterodina en relacion con mirabegron, desde la perspectiva del Sistema Nacional de Salud (SNS) espanol. Metodos Se desarrollo un modelo de arbol de decision para representar un proceso clinico tipico de tratamiento de 52 semanas para un paciente con VH con incontinencia urinaria de urgencia (IUU) iniciando el tratamiento de primera linea con fesoterodina 4 mg, incluyendo valoracion opcional a 8 mg frente a mirabegron 50 mg. Los datos de eficacia se obtuvieron de un metaanalisis de tratamiento indirecto bayesiano. Los pacientes con IUU de menos de un episodio/dia fueron definidos como respondedor al tratamiento, y la persistencia se evaluo en las semanas 4, 12 y 24. En la semana 12 los no respondedores interrumpieron el tratamiento de forma permanente. Los anos de vida ajustados por calidad (AVAC) se calcularon sobre la base de tiempo de permanencia en estados de respondedores y no respondedores. Los costes de la medicina relacionada con la VH y atencion medica, incluyendo visitas medicas, pruebas de laboratorio, compresas para la incontinencia y comorbilidades (fractura, infeccion de la piel, infecciones del tracto urinario y depresion) se modelaron y expresaron en 2015 €. Resultados En la semana 52 el porcentaje de respondedores fue de 20,8% para los pacientes que comienzan con 4 mg de fesoterodina, que opcionalmente valoro a 8 mg, y de 19,4% para los pacientes tratados con mirabegron. Los AVAC fueron ligeramente superiores con fesoterodina que con mirabegron (0,7703 vs. 0,7668, diferencia = 0,0035). El tratamiento con fesoterodina tambien tenia costes totales ligeramente mayores que mirabegron (3.296 € vs. 3.217, diferencia = 79 €), lo que resulta en un coste de 22.523/AVAC € ganado para la fesoterodina frente al mirabegron. El analisis de sensibilidad probabilistico confirmo la ligera ventaja de la fesoterodina, con un 61,1% de probabilidad de ser rentable en la disposicion a pagar de 30.000 € para un umbral de AVAC. Conclusiones Dada la relativamente pequena diferencia de coste de un ano entre los 2 tratamientos, la fesoterodina puede considerarse una opcion rentable en relacion con mirabegron para el manejo de primera linea de la VH con IUU en Espana.

Commentary to low-energy shock wave therapy ameliorates erectile dysfunction in a pelvic neurovascular injuries rat model, published in J Sex Med 2016;13:22-32 by Li H, Matheu P, Sun F, et al.

Abstract: Low-energy shockwaves (LESW) have been widely used to treat musculoesketal disorders and the therapeutic application of this technology is currently expanding to treat vasculogenic erectile dysfunction (ED) of varying severity and different etiologies, and also ischemic heart disease.

Revealing the production process of Joaquín Albarrán's Les Tumeurs de la Vessie 125 years after its writing ☆

Abstract: Objective Investigate how in 1891 Joaquin Albarran organized and wrote his Les Tumeurs de la Vessie , a manuscript printed by Georges Steinheil in 1892. Material and methods An analysis was conducted of the manuscript that compiles the casuistry set forth in the work, which helps us understand his production process. The contents of the text are analyzed, revealing the originality and value of the text in the manuscript. Results The book describes the author's personal histopathology findings from surgical and autopsied cases in Necker Hospital between 1868 and 1891: 28 numbered autopsy specimens and 67 identified by the patient's name (or, in lieu thereof, the physician's name, bed, ward and date of surgery). The notebook also contains the preliminary design of a number of photomicrographs printed in the book. Histopathology data are provided on the classification of bladder cancer, the pathway of lymphocytic spread, the genesis of cancer, tumoural heterogeneity and a number of original descriptions (squamous cell carcinoma, Von Brunn nests). Other notable clinical concepts include diagnostic symptomatology, prognosis assessment, extirpation by vesical height (with primary closure of the bladder and abdominal wall), the role of nascent endoscopic tumor extirpation and the experimental development of radical cystectomy with urinary diversion. Conclusions Joaquin Albarran analyzed his experience and that of professors Reverdin, Guyon and Horteloup. He reviewed autopsies and surgical specimens from patients and performed the histopathology study in each case. The main original observations from the work are discussed.

Case Report: Efficacy of dobesilate in insertional Achilles tendinopathy

Abstract: Achilles tendinopathy is an overuse syndrome, common among runners, with sometimes considerable negative impact on their performance, overall health, and well-being. Our report shows that local injection of an aqueous solution of the diethylammonium salt of dobesilate, an inhibitor of fibroblast growth factor with significant anti-angiogenic and anti-inflammatory effects, is effective in reducing vascular density and pain in insertional Achilles tendinopathy.

Intraarticular administration of dobesilate for the treatment of knee rheumatoid arthritis

Abstract: Rheumatoid arthritis is an inflammatory condition that causes a negative effect in patient well-being. Fibroblast growth factor participates in the pathology of rheumatoid arthritis through its proliferative, inflammatory and angiogenic activities. Dobesilate, an inhibitor of fibroblast growth factor shows marked anti-proliferative, anti-inflammatory, and anti-angiogenic activities. Our study shows that intraarticular application of dobesilate is effective in reducing symptoms and signs in patients with chronic knee rheumatoid arthritis.

Long-term prostate-specific antigen contamination in the Spanish arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC)

Abstract: Objectives Recently, the European Randomized Study of Screening for Prostate Cancer achieved a reduction in prostate cancer mortality by measuring serum prostate-specific antigen (PSA) levels. These results were not reproduced in the Spanish arm of European Randomized Study of Screening for Prostate Cancer. PSA contamination (opportunistic measurements outside the study) could decrease the study's contrasting power if performed in the control arm. We have calculated the long-term rate of PSA contamination and its effect on performing prostate biopsy and detecting cancer. Material and methods A total of 4276 men were randomized (2415 to the screening arm, 1861 to the control arm) in the Spanish section of the European Randomized Study of Screening for Prostate Cancer. PSA measurements were not scheduled in the control arm. Sextant prostate biopsy was indicated if PSA levels were ≥3 ng/ml. All PSA readings performed outside the study were labeled as “PSA contamination”. We calculated the rates of PSA contamination, biopsy implementation and cancer detection. Results The median age and follow-up time were 57 and 15.1 years, respectively. A total of 2511 men underwent at least one PSA reading outside the study. PSA contamination at 5, 10 and 15 years was 22.0%, 47.1% and 66.3% in the screening arm, respectively, and 20.8%, 43.2% and 58.6% in the control arm, respectively ( p p p = 0.0006). Conclusions Although the cumulative PSA contamination was pronounced in the 2 study arms, the rate of prostate biopsies was low in the control arm. We therefore believe that the effect of PSA contamination on the study's statistical power should be limited.

Desvelando el proceso de producción de Les Tumeurs de la Vessie de Joaquín Albarrán 125 años después de su escritura

Abstract: Resumen Objetivo Investigar como Joaquin Albarran organizo y escribio en 1891 Les Tumeurs de la Vessie , obra impresa por Georges Steinheil en 1892. Material y metodos Analisis del manuscrito que compila la casuistica expuesta en la obra y permite entender su proceso de produccion. Se analizan los contenidos del texto, y se pone en evidencia la originalidad y el valor del mismo en el tratado. Resultados El cuaderno ordena y describe hallazgos histopatologicos realizados personalmente por el autor sobre casos intervenidos o autopsiados en el Hospital Necker entre 1868 y 1891: 28 especimenes numerados de autopsia y 67 identificados por el nombre del paciente (o en su defecto medico, cama y pabellon, y fecha de intervencion). El cuaderno contiene tambien el diseno preliminar de algunas microfotografias impresas en el libro. Se aportan datos histopatologicos sobre la clasificacion del cancer vesical, la via de extension linfatica, la genesis del cancer, la heterogeneidad tumoral y algunas descripciones originales (carcinoma epidermoide, nidos de Von Brunn). Otros conceptos clinicos destacados en la obra son la semiologia diagnostica, la evaluacion del pronostico, la extirpacion por talla vesical con cierre primario de vejiga y pared abdominal, el papel de la naciente extirpacion endoscopica del tumor y el desarrollo experimental de la cistectomia radical con derivacion urinaria. Conclusiones Joaquin Albarran analizo su experiencia y la de los profesores Reverdin, Guyon y Horteloup. Reviso autopsias y especimenes quirurgicos de pacientes intervenidos y realizo el estudio histopatologico en cada caso. Se discuten las principales observaciones originales de la obra.