Serum phosphate is associated with increased risk of bone fragility fractures in hemodialysis patients.

BACKGROUND: Bone fragility fractures are associated with high morbidity and mortality. This study analysed the association between the current biochemical parameters of CKD-MBD and bone fragility fractures in the COSMOS project. METHODS: COSMOS is a 3-year, multicentre, open cohort, prospective, observational study carried out in 6797 hemodialysis patients (227 centres from 20 European countries). The association of bone fragility fractures (outcome) with serum calcium, phosphate and PTH (exposure), was assessed using Standard Cox proportional hazards regression and Cox proportional hazards regression for recurrent events. Additional analyses were performed considering all-cause mortality as a competitive event for bone fragility fracture occurrence. Multivariable models were used in all strategies, with the fully adjusted model including a total of 24 variables. RESULTS: During a median follow-up of 24 months 252 (4%) patients experienced at least one bone fragility fracture (incident bone fragility fracture rate 28.5 per 1000 patient-years). In the fractured and non-fractured patients, the percentage of men was 43.7% and 61.4%, mean age 68.1 and 63.8 years and a haemodialysis vintage of 55.9 and 38.3 months respectively. Baseline serum phosphate > 6.1 mg/dL (reference value 4.3-6.1 mg/dL) was significantly associated with a higher bone fragility fracture risk in both regression models (HR: 1.53[95%CI: 1.10-2.13] and HR: 1.44[95%CI: 1.02-2.05]. The significant association persisted after competitive risk analysis (subHR: 1.42[95%CI: 1.02-1.98]) but the finding was not confirmed when serum phosphate was considered as a continuous variable. Baseline serum calcium showed no association with bone fragility fracture risk in any regression model. Baseline serum PTH > 800 pg/mL was significantly associated with a higher bone fragility fracture risk in both regression models, but the association disappeared after a competitive risk analysis. CONCLUSIONS: Hyperphosphatemia was independently and consistently associated with an increased bone fracture risk, suggesting serum phosphate could be a novel risk factor for bone fractures in hemodialysis patients.

Redox Metabolism and Vascular Calcification in Chronic Kidney Disease.

Vascular calcification (VC) is a common complication in patients with chronic kidney disease which increases their mortality. Although oxidative stress is involved in the onset and progression of this disorder, the specific role of some of the main redox regulators, such as catalase, the main scavenger of H2O2, remains unclear. In the present study, epigastric arteries of kidney transplant recipients, a rat model of VC, and an in vitro model of VC exhibiting catalase (Cts) overexpression were analysed. Pericalcified areas of human epigastric arteries had increased levels of catalase and cytoplasmic, rather than nuclear runt-related transcription factor 2 (RUNX2). In the rat model, advanced aortic VC concurred with lower levels of the H2O2-scavenger glutathione peroxidase 3 compared to controls. In an early model of calcification using vascular smooth muscle cells (VSMCs), Cts VSMCs showed the expected increase in total levels of RUNX2. However, Cts VMSCs also exhibited a lower percentage of the nucleus stained for RUNX2 in response to calcifying media. In this early model of VC, we did not observe a dysregulation of the mitochondrial redox state; instead, an increase in the general redox state was observed in the cytoplasm. These results highlight the complex role of antioxidant enzymes as catalase by regulation of RUNX2 subcellular location delaying the onset of VC.

Evaluation of Matrix Metalloproteases by Artificial Intelligence Techniques in Negative Biopsies as New Diagnostic Strategy in Prostate Cancer.

Usually, after an abnormal level of serum prostate-specific antigen (PSA) or digital rectal exam, men undergo a prostate needle biopsy. However, the traditional sextant technique misses 15-46% of cancers. At present, there are problems regarding disease diagnosis/prognosis, especially in patients' classification, because the information to be handled is complex and challenging to process. Matrix metalloproteases (MMPs) have high expression by prostate cancer (PCa) compared with benign prostate tissues. To assess the possible contribution to the diagnosis of PCa, we evaluated the expression of several MMPs in prostate tissues before and after PCa diagnosis using machine learning, classifiers, and supervised algorithms. A retrospective study was conducted on 29 patients diagnosed with PCa with previous benign needle biopsies, 45 patients with benign prostatic hyperplasia (BHP), and 18 patients with high-grade prostatic intraepithelial neoplasia (HGPIN). An immunohistochemical study was performed on tissue samples from tumor and non-tumor areas using specific antibodies against MMP -2, 9, 11, and 13, and the tissue inhibitor of MMPs -3 (TIMP-3), and the protein expression by different cell types was analyzed to which several automatic learning techniques have been applied. Compared with BHP or HGPIN specimens, epithelial cells (ECs) and fibroblasts from benign prostate biopsies before the diagnosis of PCa showed a significantly higher expression of MMPs and TIMP-3. Machine learning techniques provide a differentiable classification between these patients, with greater than 95% accuracy, considering ECs, being slightly lower when considering fibroblasts. In addition, evolutionary changes were found in paired tissues from benign biopsy to prostatectomy specimens in the same patient. Thus, ECs from the tumor zone from prostatectomy showed higher expressions of MMPs and TIMP-3 compared to ECs of the corresponding zone from the benign biopsy. Similar differences were found for expressions of MMP-9 and TIMP-3, between fibroblasts from these zones. The classifiers have determined that patients with benign prostate biopsies before the diagnosis of PCa showed a high MMPs/TIMP-3 expression by ECs, so in the zone without future cancer development as in the zone with future tumor, compared with biopsy samples from patients with BPH or HGPIN. Expression of MMP -2, 9, 11, and 13, and TIMP-3 phenotypically define ECs associated with future tumor development. Also, the results suggest that MMPs/TIMPs expression in biopsy tissues may reflect evolutionary changes from prostate benign tissues to PCa. Thus, these findings in combination with other parameters might contribute to improving the suspicion of PCa diagnosis.

Prostate Cancer Tumor Stroma: Responsibility in Tumor Biology, Diagnosis and Treatment.

Prostate cancer (PCa) is a common cancer among males globally, and its occurrence is growing worldwide. Clinical decisions about the combination of therapies are becoming highly relevant. However, this is a heterogeneous disease, ranging widely in prognosis. Therefore, new approaches are needed based on tumor biology, from which further prognostic assessments can be established and complementary strategies can be identified. The knowledge of both the morphological structure and functional biology of the PCa stroma compartment can provide new diagnostic, prognostic or therapeutic possibilities. In the present review, we analyzed the aspects related to the tumor stromal component (both acellular and cellular) in PCa, their influence on tumor behavior and the therapeutic response and their consideration as a new therapeutic target.

Gene Expression Profile of Stromal Factors in Cancer-Associated Fibroblasts from Prostate Cancer.

Recent investigations point at the stromal microenvironment to assess additional diagnostic information and provide new therapeutic targets in cancer. The aim of the study was to contribute to the characterization of the phenotype of cancer-associated fibroblasts (CAFs) in prostate cancer (PCa) compared with normal prostate-associated fibroblasts (NAFs) and fibroblasts from benign prostatic hyperplasia (BPH). Three patient populations were prospectively recruited: 23 patients with new localized PCa, 14 patients with advanced PCa treated with androgenic deprivation therapy (ADT), and 7 patients with BPH. Gene expression of 20 stroma-derived factors, including the androgen receptor (AR), chaperones (HSPA1A and HSF1), growth factors (FGF2, FGF7, FGF10, HGF, PDGFB, and TGFß), proteins implicated in invasion (MMP2, MMP9, and MMP11), inflammation (IL6, IL17RB, NFκB, and STAT3), and in-stroma/epithelium interaction (CDH11, CXCL12, CXCL14, and FAP), was evaluated. Localized PCa CAFs showed a significant higher expression of FGF7, IL6, MMP2, and MMP11 compared with NAFs or IL17RB compared with BPH fibroblasts, but significantly lower expression of FGF10 and IL17RB compared with NAFs or CXCL14 compared with BPH fibroblasts. In addition, CAFs from ADT-resistant PCa showed significantly higher MMP11 and NFκB but significant lower TGFß expression compared with CAFs from ADT-sensitive tumors. Our results contribute to defining the CAFs phenotypes associated to PCa progression, which may contribute to the diagnosis and design of alternative therapies in PCa.

Efficacy and Tolerability of 6-Month Treatment with Tamsulosin Plus the Hexanic Extract of Serenoa repens versus Tamsulosin Plus 5-Alpha-Reductase Inhibitors for Moderate-to-Severe LUTS-BPH Patients: Results of a Paired Matched Clinical Study.

The objective of this subset analysis was to evaluate and compare the efficacy and tolerability of two combination treatments for men with moderate-to-severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). Data were from a real-world, open-label, prospective, and multicenter study performed in outpatient urology clinics. Men with moderate-to-severe LUTS/BPH received 6-month treatment with tamsulosin (TAM) in combination with either the hexanic extract of S. repens (HESr) or a 5-alpha-reductase inhibitor (5ARI). Changes in urinary symptoms and quality of life were measured using the IPSS and BII questionnaires, respectively. Treatment tolerability was assessed by recording adverse effects (AEs). Patients in the two study groups were matched using iterative and propensity score matching approaches. After iterative matching, data were available from 136 patients (n = 68 treated with TAM + 5ARI, n = 68 with TAM + HESr). After 6 months of treatment, mean (SD) IPSS total score improved by 7.7 (6.3) and 6.7 (5.0) points in the TAM + 5ARI and TAM + HESr groups, respectively (p = 0.272); mean BII total scores improved by 3.1 (2.9) and 2.9 (2.4) points (p = 0.751), respectively. AEs were reported by 26.5% and 10.3% of patients in the same groups, mostly affecting sexual function (p < 0.027). When used in a real-world setting to treat patients with moderate-severe LUTS/BPH, 6-month treatment with TAM + HESr was as effective as TAM + 5ARI, but with better tolerability.

Efficacy and Safety of the Hexanic Extract of Serenoa repens vs. Watchful Waiting in Men with Moderate to Severe LUTS-BPH: Results of a Paired Matched Clinical Study.

We investigated changes in symptoms and quality of life (QoL) in men with moderate-to-severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) receiving the hexanic extract of Serenoa repens (HESr) and compared results with a matched group on watchful waiting (WW). Data was from a real-world, open-label, prospective, multicenter study. This sub-group analysis included patients with moderate-to-severe symptoms receiving either the HESr 320 mg/daily for six months (HESr) or who remained untreated for LUTS/BPH (WW). Changes in urinary symptoms and QoL were measured by IPSS and BII questionnaires. Two statistical approaches (iterative matching and propensity score pairing) were used to maximize between-group comparability at baseline. Tolerability was assessed in the HESr group. After iterative matching, data for analysis was available for 783 patients (102 WW, 681 HESr). IPSS scores improved by a mean (SD) of 3.8 (4.4) points in the HESr group and by 2.2 (4.5) points in the WW group (p = 0.002). Changes in BII score were 1.8 (2.4) points and 1.0 (2.2) points, respectively (p < 0.001). Three patients (0.9%) treated with the HESr reported mild adverse effects. Moderate-severe LUTS/BPH patients treated for six months with the HESr showed greater improvements in symptoms and QoL than matched patients on WW, with a very low rate of adverse effects.

Efficacy and tolerability of the hexanic extract of Serenoa repens compared to tamsulosin in moderate-severe LUTS-BPH patients.

In a subset analysis of data from a 6-month, multicenter, non-interventional study, we compared change in symptoms and quality of life (QoL), and treatment tolerability, in men with moderate to severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) receiving tamsulosin (TAM, 0.4 mg/day) or the hexanic extract of Serenoa repens (HESr, 320 mg/day) as monotherapy. Symptoms and QoL were assessed using the IPSS and BII questionnaires, respectively. Patients in the treatment groups were matched using two statistical approaches (iterative and propensity score matching). Within the iterative matching approach, data was available from a total of 737 patients (353 TAM, 384 HESr). After 6 months, IPSS scores improved by a mean (SD) of 5.0 (4.3) points in the TAM group and 4.5 (4.7) points in the HESr group (p = 0.117, not significant). Improvements in QoL were equivalent in the two groups. TAM patients reported significantly more adverse effects than HESr patients (14.7% vs 2.1%; p < 0.001), particularly ejaculation dysfunction and orthostatic hypotension. These results show that HESr is a valid treatment option for men with moderate/severe LUTS/BPH; improvements in urinary symptoms and QoL were similar to those observed for tamsulosin, but with considerably fewer adverse effects.

Clinical Benefit of Tamsulosin and the Hexanic Extract of Serenoa Repens, in Combination or as Monotherapy, in Patients with Moderate/Severe LUTS-BPH: A Subset Analysis of the QUALIPROST Study.

To investigate whether tamsulosin (TAM) and the hexanic extract of Serenoa repens (HESr) are more effective in combination than as monotherapy in men with moderate-to-severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). Subset analysis of data from a 6-month, multicenter observational study. Patients received either tamsulosin (0.4 mg/day) or HESr (320 mg/day) alone or in combination. Primary endpoints were change in symptoms and quality of life. Tolerability was also assessed. Seven hundred and nine patients were available for intention to treat (ITT) analysis, 263 treated with tamsulosin, 262 with HESr, and 184 with TAM + HESr. After 6 months, International Prostate Symptom Score (IPSS) scores improved by a mean (standard deviation) of 7.2 (5.0) points in the TAM + HESr group compared to 5.7 (4.3) points with TAM alone and 5.4 (4.6) points with HESr (p < 0.001). Quality of life showed greatest improvement with combination therapy (p < 0.02). Adverse effects were reported by 1.9% of patients receiving HESr, 13.3% receiving TAM, and 12.0% receiving TAM + HESr (p < 0.001). In men with moderate/severe LUTS/BPH, combination treatment with TAM + HESr produced more effective symptom relief and greater improvement in quality of life than with either treatment alone, with acceptable tolerability.

Análisis comparativo de la expresión de metaloproteasas (MMP-2, MMP-9, MMP-11 y MMP-13) y del inhibidor tisular de la metaloproteasa 3 (TIMP-3) entre las biopsias previas negativas y las prostatectomías radicales / Comparative analysis of the expression of metalloproteases (MMP-2, MMP-9, MMP-11 and MMP-13) and the tissue inhibitor of metalloprotease 3 (TIMP-3) between previous negative biopsies and radical prostatectomies

Las metaloproteasas (MMP) y el inhibidor tisular de metaloproteasas 3 (TIMP-3) se han relacionado con el riesgo de padecer cáncer y con la agresividad de varios tumores. En ocasiones, existen muchas dificultades para diagnosticar el cáncer de próstata y la expresión de MMP y del TIMP-3 en biopsias negativas nos podría ayudar a realizar una sospecha diagnóstica en estos casos. El objetivo es hacer un estudio comparativo de la expresión de MMP y TIMP-3 en las biopsias previas negativas y las prostatectomías radicales (PR). MATERIAL Y MÉTODOS: Análisis retrospectivo de una cohorte de base hospitalaria que incluye a 21 pacientes con sospecha de carcinoma prostático en los que se analizaron por técnica inmunohistoquímica las expresiones de MMP-2, 9, 11 y 13 y el TIMP-3 en la zona tumoral, tanto de las biopsias previas negativas como de las PR. RESULTADOS: Los valores de tinción inmunohistoquímicos (score) para las MMP (-11 y -13) y TIMP-3 no mostraron diferencias significativas al comparar las áreas de las biopsias negativas donde luego se desarrolló tumor con las de la PR. Sin embargo, sí que observamos una diferencia significativa aumentando la expresión de la MMP-2 (p = 0,002) y MMP-9 (p = 0,001) en la zona tumoral de la PR con respecto al área correspondiente de la biopsia previa negativa. CONCLUSIONES: Nuestros datos indican una mayor expresión global de la MMP-2 y la MMP-9 en la zona tumoral de la PR en comparación con las áreas correspondientes de la biopsia previa negativa, lo que parece estar en relación con el proceso de transformación maligna

Metalloproteases (MMPs) and tissue inhibitor of metalloprotease-3 (TIMP-3) have been associated to the risk of having cancer and tumor aggressiveness. When facing the difficulties of prostate cancer diagnosis, the expression of MMPs and TIMP-3 in negative biopsies could be helpful to evaluate a diagnostic suspicion. Our objective is to carry out a comparative study of the expression of MMPs and TIMP-3 in previous negative biopsies and radical prostatectomies (RP). MATERIAL AND METHODS: Retrospective analysis of a hospital-based cohort including 21 patients with suspicion of prostate carcinoma, whose expressions of MMP-2, 9, 11 and 13 and TIMP-3 were evaluated by immunohistochemistry in the tumor area from previous negative biopsies and RP. RESULTS: Immunohistochemical staining values (Score) for MMPs (-11 and -13) and TIMP-3 showed no significant differences when comparing the areas of negative biopsies where tumors subsequently developed with those of the RP. However, we did observe a significant difference in the increased expression of MMP-2 (P = .002) and MMP-9 (P = .001) in the tumor area of the RP with respect to the corresponding area of the previous negative biopsy. CONCLUSIONS: Our data indicate a higher overall expression of MMP-2 and MMP-9 in the tumor area of the RP compared to the corresponding areas of the negative previous biopsy, which seems to be associated to the process of malignant transformation

[Incidence of genitourinary pathology in the emergency department.] / Incidencia de la patología genitourinaria en urgencias.

OBJECTIVE: The increase of healthcare pressure in Emergency Departments compels us to have a better understanding of patients' characteristics and the pathology they consult for. This is the first study that estimates the waiting time in the emergency room and the factors that are independently related with hospital admission. METHODS: Descriptive and retrospective study of 2.741 patients who were admitted to the Emergency Department with genitourinary symptoms in 2011. Clinical and epidemiological features were reviewed. A multivariable study was performed to identify the factors related with the final resolution of patients, recurrence emergency attendance, and waiting time in the emergency room. RESULTS: Most of the patients were male (60.3%), being diagnosed with hematuria, acute urinary retention and genital pathology. Females complained more frequently for pyelonephritis, urinary tract infection and low-back pain. Male were hospitalized in greater proportion. Age, diagnosis of infection/sepsis or low-back pain, and yellow or orange MTS level were independent features for hospital admission. Also, in the univariate and multivariate study, age > 60 years (311 vs 220 min.), UTI/sepsis related diagnoses (300 vs 250 min.), and hospital admission as final resolution (440 vs 240 min.) had a significant influence in the waiting time in the Emergency Department. CONCLUSIONS: Age over 60 years, hospital admission as final resolution and infection/sepsis diagnosis were independent features for further waiting time in the Emergency Department. Persistent pain and symptoms of infection/sepsis behaved as independent features for hospital admission.

OBJETIVO: El aumento de la presión asistencial de los servicios de urgencias hospitalarios obliga a conocer las características de los pacientes y de los procesos por los que acuden. Este estudio es el primero que calcula tiempo de permanencia en urgencias y factores que se relacionan de manera independiente con ingreso hospitalario.MÉTODOS: Estudio descriptivo y retrospectivo de 2.741 pacientes que acudieron a Urgencias por sintomatología genitourinaria en el año 2011. Se examinaron rasgos clínicos y epidemiológicos. Se realizó un análisis multivariable para conocer los factores relacionados con la resolución final de los pacientes, recurrencia en la asistencia a urgencias y tiempo en urgencias. RESULTADOS: La mayoría de pacientes fueron varones (60,3%), con diagnósticos de hematuria, RAO y patología genital. Las mujeres, presentaron pielonefritis, ITU y dolor lumbar de manera más frecuente. Los varones ingresaron en mayor proporción. La edad, el diagnóstico de infección/sepsis o dolor lumbar y un nivel MTS amarillo o naranja, resultaron ser factores independientes de ingreso. Tanto en el estudio univariable como multivariable, la edad mayor de 60 años (311 vs 220 min), los diagnósticos relacionados con ITU y sepsis (300 vs 250 min) y el ingreso hospitalario como resolución final (440 vs 240 min) influyeron de forma significativa en el tiempo de estancia en Urgencias. CONCLUSIONES: La edad > 60 años, el resultado de ingreso y el diagnóstico de infección/sepsis fueron factores independientes de mayor tiempo en Urgencias. La presencia de dolor persistente y de infección/sepsis se comportaron como factores independientes de ingreso.

Pain and Distraction According to Sensory Modalities: Current Findings and Future Directions.

BACKGROUND: This review discusses the findings in the literature on pain and distraction tasks according to their sensory modality. Distraction tasks have been shown to reduce (experimentally induced) acute pain and chronic pain. This can be influenced by nature and by the sensory modalities used in the distraction tasks. Yet the effect on reducing pain according to the sensory modality of the distraction task has received little attention. METHODS: A bibliographic search was performed in different databases. The studies will be systematized according to the sensory modality in which the distraction task was applied. RESULTS: The analyzed studies with auditory distractors showed a reduction of acute pain in adults. However, these are not effective at healthy children and in adults with chronic pain. Visual distractors showed promising results in acute pain in adults and children. Similarly, tactile and mixed distractors decreased acute pain in adults. CONCLUSION: Distraction tasks by diverse sensory modalities have a positive effect on decreasing the perception of acute pain in adults. Future studies are necessary given the paucity of research on this topic, particularly with tactile distractors (there is only one study). Finally, the most rigorous methodology and the use of ecological contexts are encouraged in future research.

Incidencia de la patología genitourinaria en urgencias / Incidence of genitourinary pathology in the emergency department

Objetivo: El aumento de la presión asistencial de los servicios de urgencias hospitalarios obliga a conocer las características de los pacientes y de los procesos por los que acuden. Este estudio es el primero que calcula tiempo de permanencia en urgencias y factores que se relacionan de manera independiente con ingreso hospitalario. Métodos: Estudio descriptivo y retrospectivo de 2.741 pacientes que acudieron a Urgencias por sintomatología genitourinaria en el año 2011. Se examinaron rasgos clínicos y epidemiológicos. Se realizó un análisis multivariable para conocer los factores relacionados con la resolución final de los pacientes, recurrencia en la asistencia a urgencias y tiempo en urgencias. Resultados: La mayoría de pacientes fueron varones (60,3%), con diagnósticos de hematuria, RAO y patología genital. Las mujeres, presentaron pielonefritis, ITU y dolor lumbar de manera más frecuente. Los varones ingresaron en mayor proporción. La edad, el diagnóstico de infección/sepsis o dolor lumbar y un nivel MTS amarillo o naranja, resultaron ser factores independientes de ingreso. Tanto en el estudio univariable como multivariable, la edad mayor de 60 años (311 vs 220 min), los diagnósticos relacionados con ITU y sepsis (300 vs 250 min) y el ingreso hospitalario como resolución final (440 vs 240 min) influyeron de forma significativa en el tiempo de estancia en Urgencias. Conclusiones: La edad > 60 años, el resultado de ingreso y el diagnóstico de infección/sepsis fueron factores independientes de mayor tiempo en Urgencias. La presencia de dolor persistente y de infección/sepsis se comportaron como factores independientes de ingreso

Objective: The increase of healthcare pressure in Emergency Departments compels us to have a better understanding of patients' characteristics and the pathology they consult for. This is the first study that estimates the waiting time in the emergency room and the factors that are independently related with hospital admission. Methods: Descriptive and retrospective study of 2.741 patients who were admitted to the Emergency Department with genitourinary symptoms in 2011. Clinical and epidemiological features were reviewed. A multivariable study was performed to identify the factors related with the final resolution of patients, recurrence in emergency attendance, and waiting time in the emergency room. Results: Most of the patients were male (60.3%), being diagnosed with hematuria, acute urinary retention and genital pathology. Females complained more frequently for pyelonephritis, urinary tract infection and low-back pain. Male were hospitalized in greater proportion. Age, diagnosis of infection/sepsis or low-back pain, and yellow or orange MTS level were independent features for hospital admission. Also, in the univariate and multivariate study, age > 60 years (311 vs 220 min.), UTI/sepsis related diagnoses (300 vs 250 min.), and hospital admission as final resolution (440 vs 240 min.) had a significant influence in the waiting time in the Emergency Department. Conclusions: Age over 60 years, hospital admission as final resolution and infection/sepsis diagnosis were independent features for further waiting time in the Emergency Department. Persistent pain and symptoms of infection/sepsis behaved as independent features for hospital admission

Revisión de la evidencia sobre el manejo de medicamentos y productos peligrosos en los servicios de Urología; documento de consenso entre la Asociación Española de Urología y la Sociedad Española de Farmacia Hospitalaria / Review of evidence on handling hazardous drugs and Products in Urology Services; consensus document between the Spanish Urology Association and the Spanish Society of Health-System Pharmacists

Objetivo: La administración intravesical de medicamentos peligrosos es una práctica habitual en el ámbito de la urología, con posible exposición del personal sanitario a dichos medicamentos. Se considera necesario disponer de un documento de consenso entre las sociedades científicas implicadas -Asociación Española de Urología y Sociedad Española de Farmacia Hospitalaria- que recoja la mejor evidencia disponible para el manejo, de la forma más segura posible, de medicamentos peligrosos en el ámbito de los servicios de Urología. Método: Se ha realizado una revisión de la legislación y de las recomendaciones sobre el manejo de medicamentos peligrosos tanto a nivel estatal como internacional. Resultados: Se dispone de legislación nacional y de normativas para la protección de los trabajadores que manipulen medicamentos y productos peligrosos, así como recomendaciones de manipulación para la protección tanto del producto, como de los trabajadores

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

Review of evidence on handling hazardous drugs and Products in Urology Services; consensus document between the Spanish Urology Association and the Spanish Society of Health-System Pharmacists.

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.

Objetivo: La administración intravesical de medicamentos peligrosos es una  práctica habitual en el ámbito de la urología, con posible exposición del personal  sanitario a dichos medicamentos. Se considera necesario disponer de un  documento de consenso entre las sociedades científicas implicadas ­Asociación  Española de Urología y Sociedad Española de Farmacia Hospitalaria­ que recoja la mejor evidencia disponible para el manejo, de la forma más segura posible,  de medicamentos peligrosos en el ámbito de los servicios de Urología.Método: Se ha realizado una revisión de la legislación y de las recomendaciones sobre el manejo de medicamentos peligrosos tanto a nivel estatal como internacional.Resultados: Se dispone de legislación nacional y de normativas para la  protección de los trabajadores que manipulen medicamentos y productos peligrosos, así como recomendaciones de manipulación para la protección tanto del producto, como de los trabajadores.Discusión: Siguiendo las líneas estratégicas del Parlamento Europeo para el  período 2014-2020 en el capítulo de seguridad y salud laboral, la Asociación Española de Urología y la Sociedad Española de Farmacia Hospitalaria proponen una serie de actuaciones que hagan disminuir los riesgos de exposición de los profesionales y cuidadores implicados en su manejo. Conclusiones: Tras esta revisión se establecen 19 recomendaciones para el  manejo de medicamentos peligrosos que pueden resumirse en la necesidad de  formación de todas las personas implicadas (desde los equipos directivos hasta  los pacientes y cuidadores), la adopción de sistemas que no permitan fugas  contaminantes, programas de vigilancia de las exposiciones y optimización de  los recursos disponibles.

Efficacy and safety of a hexanic extract of Serenoa repens (Permixon® ) for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH): systematic review and meta-analysis of randomised controlled trials and observational studies.

OBJECTIVES: To comprehensively evaluate the efficacy and safety of the hexanic extract of Serenoa repens (HESr, Permixon® ; Pierre Fabre Médicament, Castres, France), at a dose of 320 mg daily, as monotherapy for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) and prospective observational studies in patients with LUTS/BPH identified through searches in Medline, Web of Knowledge (Institute for Scientific Information), Scopus, the Cochrane Library, and bibliographic references up to March 2017. Articles studying S. repens extracts other than Permixon were excluded. Data were collected on International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax ), nocturia, quality of life, prostate volume, sexual function, and adverse drug reactions (ADRs). Data obtained from RCTs and observational studies were analysed jointly and separately using a random effects model. A sub-group analysis was performed of studies that included patients on longer-term treatment (≥1 year). RESULTS: Data from 27 studies (15 RCTs and 12 observational studies) were included for meta-analysis (total N = 5 800). Compared with placebo, the HESr was associated with 0.64 (95% confidence interval [CI] -0.98 to -0.31) fewer voids/night (P < 0.001) and an additional mean increase in Qmax of 2.75 mL/s (95% CI 0.57 to 4.93; P = 0.01). When compared with α-blockers, the HESr showed similar improvements on IPSS (weighted mean difference [WMD] 0.57, 95% CI -0.27 to 1.42; P = 0.18) and a comparable increase in Qmax to tamsulosin (WMD -0.02, 95% CI -0.71 to 0.66; P = 0.95). Efficacy assessed using the IPSS was similar after 6 months of treatment between the HESr and 5α-reductase inhibitors (5ARIs). Analysis of all available published data for the HESr showed a mean improvement in IPSS from baseline of -5.73 points (95% CI -6.91 to -4.54; P < 0.001). HESr did not negatively affect sexual function and no clinically relevant effect was observed on prostate-specific antigen. Prostate volume decreased slightly. Similar efficacy results were seen in patients treated for ≥1 year (n = 447). The HESr had a favourable safety profile, with gastrointestinal disorders being the most frequent ADR (mean incidence of 3.8%). CONCLUSION: The present meta-analysis, which includes all available RCTs and observational studies, shows that the HESr (Permixon) reduced nocturia and improved Qmax compared with placebo and had a similar efficacy to tamsulosin and short-term 5-ARI in relieving LUTS. HESr (Permixon) appears to be an efficacious and well-tolerated therapeutic option for the long-term medical treatment of LUTS/BPH.

Stromal factors involved in human prostate cancer development, progression and castration resistance.

PURPOSE: To detect new predictive markers from the prostate cancer tissue, to study the expression by cultured cancer-associated fibroblasts (CAFs) of stromal factors implicated in prostate carcinogenesis, and to compare their expressions in localized, metastatic, castration-sensitive (CSCP), castration-resistant prostate tumors (CRCP) as well as in fibroblasts from benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: The genomic expression of 20 stroma-derived factors, including the androgen receptor (AR), growth factors (FGF2, FGF7, FGF10, HGF, TGFß, PDGFB), protein implicated in invasion (MMP-2, MMP-9 and MMP-11), inflammation (IL-6, IL-17, STAT-3 and NFκB), stroma/epithelium interaction (CDH11, FAP, CXCL12 and CXCL14) and chaperones (HPA1A and HSF1), was evaluated in cultured fibroblasts both from BHP and prostate carcinomas (PCa). After isolation and culture of fibroblasts by biopsy specimens, RNA was isolated and genomic studies performed. RESULTS: Finally, 5 BPH and 37 PCa specimens were selected: clinically localized (19), metastatic (5), CSCP (7) and CRPC (6). Interleukin-17 receptor (IL-17RB) was highly expressed in CAFs compared with fibroblasts from BPH. However, metalloproteinase-2 and chemokine ligand 14 (CXCL14) were expressed at higher levels by fibroblasts from BPH. The fibroblastic growth factor-7 was highly expressed by CAFs from localized tumors, but metalloproteinase-11 in metastatic tumors. MMP-11, androgen receptor (AR) and heat-shock-70kda-protein-1A (HSPA1A) expressions were significantly higher in CAFs from CRPC. CONCLUSIONS: These results demonstrate a CAFs heterogeneity among prostate carcinomas with regard to some molecular profile expressions that may be relevant in tumor development (IL-17RB), progression (MMP-11) and castration resistance (AR, MMP-11 and HSPA1A).

Molecular classification of non-muscle-invasive bladder cancer (pTa low-grade, pT1 low-grade, and pT1 high-grade subgroups) using methylation of tumor-suppressor genes.

The role of epigenetics in distinguishing pathological and clinical subgroups in bladder cancer is not fully characterized. We evaluated whether methylation of tumor-suppressor genes (TSGs) would classify non-muscle-invasive (NMI) bladder cancer subgroups and predict outcome. A retrospective design included the following paraffin-embedded primary NMI tumor types (n = 251): pTa low grade (LG) (n = 79), pT1LG (n = 81), and pT1 high grade (HG) (n = 91). Methylation of 25 TSGs was measured using methylation-specific, multiplex, ligation-dependent probe amplification. The TSGs most frequently methylated in the overall series were STK11 (96.8%), MGMT2 (64.5%), RARB (63.0%), and GATA5 (63.0%). TSG methylation correlated to clinicopathological variables in each subgroup and in the overall NMI series. Methylation of RARB, CD44, PAX5A, GSTP1, IGSF4 (CADM1), PYCARD, CDH13, TP53, and GATA5 classified pTa versus pT1 tumors whereas RARB, CD44, GSTP1, IGSF4, CHFR, PYCARD, TP53, STK11, and GATA5 distinguished LG versus HG tumors. Multivariate analyses indicated that PAX5A, WT1, and BRCA1 methylation independently predicted recurrence in pTaLG, PAX6, ATM, CHFR, and RB1 in pT1LG disease; PYCARD, in pT1HG disease; and PAX5A and RB1, in the overall series. Methylation of TSGs provided a molecular classification of NMI disease according to clinicopathological factors. Furthermore, TSG methylation predicted recurrence in NMI subgroups.