Revisión sistemática de la implantación de prótesis de pene en cirugía mayor ambulatoria / Systematic review of the implantation of penile prosthesis in major ambulatory surgery

Introducción y objetivo La implantación de prótesis deZ pene (PP) es una alternativa eficaz para la disfunción eréctil. Aunque inicialmente la cirugía de PP se realizaba en régimen hospitalario, existe una tendencia creciente a realizar el implante de PP en un modelo de cirugía mayor ambulatoria (CMA). El objetivo de este estudio es realizar una revisión sistemática de la literatura para identificar la evidencia disponible sobre la implantación de PP en el marco de la CMA en comparación con el procedimiento realizado en régimen hospitalario. Material y métodos Se realizó una búsqueda en las bases de datos electrónicas PubMed, EMBASE, Cochrane Library y MEDES y en los suplementos no indexados de los congresos científicos para identificar artículos relacionados con la implantación quirúrgica de PP en CMA hasta febrero de 2021. Los términos de búsqueda incluyeron prótesis de pene, disfunción eréctil, cirugía ambulatoria, atención ambulatoria y cirugía. Resultados Entre las 171 publicaciones obtenidas (51 en PubMed, 73 en EMBASE, 3 en Cochrane, 2 mediante MEDES y 42 mediante búsqueda manual), se seleccionaron finalmente 5 estudios. No hubo diferencias significativas entre la CMA y el régimen hospitalario en términos del tipo de dispositivo, el abordaje quirúrgico o la ubicación del reservorio. Las tasas de complicaciones observadas en ambos grupos fueron similares. La implantación de PP en régimen de CMA supuso un menor coste que la cirugía en régimen hospitalario y se asoció con tasas aceptables de satisfacción de los pacientes y un adecuado control del dolor. Conclusiones Los estudios demostraron que la implantación de PP en régimen de CMA puede lograr resultados similares en términos de seguridad y satisfacción a la implantación de PP en el régimen hospitalario, pudiendo también reducir los costes y mejorar la eficiencia. Esta investigación podría ayudar a los responsables de la toma de decisiones a extender la cirugía de PP al régimen ambulatorio (AU)

Introduction and objective Penile prosthesis (PP) implantation is an effective option for erectile dysfunction. Although initially PP surgery was carried out in an inpatient setting, there is a growing trend to implant PP in a major ambulatory surgery (MAS). This study aimed to perform a systematic review of the literature to identify available evidence of the implantation of PP under MAS setting and go carry out a comparison between MAS and inpatient procedures. Material and methods PubMed, EMBASE, Cochrane Library and MEDES electronic databases and non-indexed supplements for scientific congresses were searched to identify articles related to the surgical implantation of PP in MAS up to February 2021. Key search terms included penile prosthesis, erectile dysfunction, ambulatory surgery, ambulatory care, and surgery. Results Among 171 publications retrieved (51 PubMed, 73 EMBASE, 3 Cochrane, 2 using MEDES and 42 manual searching), 5 studies were finally selected. There were no significant differences between MAS or inpatient setting in terms of the type of device, surgical approach, or location of reservoir. Complication rates observed in both groups were similar. Implantation of PP in MAS was less expensive than inpatient surgery and was associated with acceptable patient satisfaction rates and adequate pain control. Conclusions Studies demonstrated that outpatient PP surgery can achieve similar outcomes in terms of safety and satisfaction to implantation of PP in the inpatient setting, while it could reduce costs and improve the efficiency. This research could provide support decision makers to extend PP surgery into the ambulatory setting (AU)

A review of the International Seabed Authority database DeepData from a biological perspective: challenges and opportunities in the UN Ocean Decade.

There is an urgent need for high-quality biodiversity data in the context of rapid environmental change. Nowhere is this need more urgent than in the deep ocean, with the possibility of seabed mining moving from exploration to exploitation, but where vast knowledge gaps persist. Regions of the seabed beyond national jurisdiction, managed by the International Seabed Authority (ISA), are undergoing intensive mining exploration, including the Clarion-Clipperton Zone (CCZ) in the Central Pacific. In 2019, the ISA launched its database 'DeepData', publishing environmental (including biological) data. Here, we explore how DeepData could support biological research and environmental policy development in the CCZ (and wider ocean regions) and whether data are findable, accessible, interoperable and reusable (FAIR). Given the direct connection of DeepData with the regulator of a rapidly developing potential industry, this review is particularly timely. We found evidence of extensive duplication of datasets; an absence of unique record identifiers and significant taxonomic data-quality issues, compromising FAIRness of the data. The publication of DeepData records on the OBIS ISA node in 2021 has led to large-scale improvements in data quality and accessibility. However, limitations in the usage of identifiers and issues with taxonomic information were also evident in datasets published on the node, stemming from mismapping of data from the ISA environmental data template to the data standard Darwin Core prior to data harvesting by OBIS. While notable data-quality issues remain, these changes signal a rapid evolution for the database and significant movement towards integrating with global systems, through the usage of data standards and publication on the global data aggregator OBIS. This is exactly what has been needed for biological datasets held by the ISA. We provide recommendations for the future development of the database to support this evolution towards FAIR. Database URL https://data.isa.org.jm/isa/map.

Systematic review of the implantation of penile prosthesis in major ambulatory surgery.

INTRODUCTION AND OBJECTIVE: Penile prosthesis (PP) implantation is an effective option for erectile dysfunction. Although initially PP surgery was carried out in an inpatient setting, there is a growing trend to implant PP as a major ambulatory surgery (MAS). This study aimed to perform a systematic review of the literature to identify available evidence of the implantation of PP under MAS setting and go carry out a comparison between MAS and inpatient procedures. MATERIAL AND METHODS: PubMed, EMBASE, Cochrane Library and MEDES electronic databases and non-indexed supplements for scientific congresses were searched to identify articles related to the surgical implantation of PP in MAS up to February 2021. Key search terms included penile prosthesis, erectile dysfunction, ambulatory surgery, ambulatory care, and surgery. RESULTS: Among 171 publications retrieved (51 PubMed, 73 EMBASE, 3 Cochrane, 2 using MEDES and 42 manual searching), 5 studies were finally selected. There were no significant differences between MAS or inpatient setting in terms of the type of device, surgical approach, or location of reservoir. Complication rates observed in both groups were similar. Implantation of PP in MAS was less expensive than inpatient surgery and was associated with acceptable patient satisfaction rates and adequate pain control. CONCLUSIONS: Studies demonstrated that outpatient PP surgery can achieve similar outcomes in terms of safety and satisfaction to implantation of PP in the inpatient setting, while it could reduce costs and improve the efficiency. This research could support decision makers to extend PP surgery into the ambulatory setting.

Opciones terapéuticas y factores predictivos de recurrencia y mortalidad cáncer-específica en pacients con tumor vesical después de traspante renal: análisis multiinstitucional / Treatment options and predictive factors for recurrence and cancer-specific mortality in bladder cancer after renal transplantation: A multi-institutional analysis

Objetivos: El tumor vesical (TV) en la población trasplantada representa un desafío debido al estado de inmunosupresión de los pacientes y a la mayor tasa de comorbilidades. El objetivo de este estudio fue analizar el tratamiento del TV tras el trasplante renal (TR), centrándose en el modo de presentación, diagnóstico, opciones de tratamiento, factores predictivos de recurrencia y mortalidad cáncer-específica. Material y métodos: Se realizó un estudio observacional prospectivo con un análisis retrospectivo de 88 pacientes con TV después de TR en 10 centros europeos. Se recogieron datos clínicos y oncológicos y se revisaron las indicaciones y los resultados del tratamiento adyuvante. Se aplicó el método de Kaplan-Meier para el análisis de la supervivencia y regresión de Cox uni- y multivariante para identificar los factores de riesgo. Resultados: En la revisión se incluyeron un total de 10.000 TR, identificando 87 pacientes con TV de novo, tras una mediana de seguimiento de 126 meses. La mediana del tiempo al diagnóstico fue 73 meses posterior al TR. Setenta y un pacientes (81,6%) fueron diagnosticados de TV no músculo-invasivo, de los cuales 29 (40,8%) recibieron tratamiento adyuvante: 6 de ellos (20,6%) recibieron el bacilo Calmette-Guérin (BCG) y 20 (68,9%) mitomicina C. En el análisis univariado los pacientes que recibieron BCG presentaron una tasa de recurrencia del TV significativamente menor (p = 0,043). En el análisis multivariante, el cambio de la inmunosupresión a inhibidores de mTOR redujo significativamente el riesgo de recurrencia (HR: 0,24; IC del 95%: 0,053-0,997; p = 0,049), mientras que la presencia de múltiples tumores lo aumentó (HR: 6,31; IC del 95%: 1,78-22,3; p = 0,004). Globalmente, 26 pacientes (29,88%) se sometieron a cistectomía, sin registrarse complicaciones mayores. La mortalidad global fue del 32,2% (28 pacientes) y la mortalidad cáncer-específica del 13,8%. Conclusiones: El tratamiento con bacilo Calmette-Guérin adyuvante y el cambio a inhibidores de mTOR reduce significativamente el riesgo de recurrencia de TV en TR, mientras que la presencia de tumores múltiples aumenta el riesgo

Objectives: Bladder cancer (BC) in the transplanted population can represent a challenge owing to the immunosuppressed state of patients and the higher rate of comorbidities. The objective was to analyze the treatment of BC after renal transplant (RT), focusing on the mode of presentation, diagnosis, treatment options and predictive factors for recurrence. Material and methods:We conducted an observational prospective study with a retrospective analysis f 88 patients with BC after RT at 10 European centers. Clinical and oncologic data were collected, and indications and results of adjuvant treatment reviewed. The Kaplan-Meier method and uni- and multivariate Cox regression analyses were performed. Results: A total of 10,000 RTs were performed. Diagnosis of BC occurred at a median of 73 months after RT. Median follow-up was 126 months. Seventy-one patients (81.6%) had non-muscle invasive bladder cancer, of whom 29 (40.8%) received adjuvant treatment; of these, six (20.6%) received bacillus Calmette-Guérin and 20 (68.9%) mitomycin C. At univariate analysis, patients who received bacillus Calmette-Guérin had a significantly lower recurrence rate (P = .043). At multivariate analysis, a switch from immunosuppression to mTOR inhibitors significantly reduced the risk of recurrence (HR 0.24, 95% CI: 0.053-0.997, P = .049) while presence of multiple tumors increased it (HR 6.31, 95% CI: 1.78-22.3, P = .004). Globally, 26 patients (29.88%) underwent cystectomy. No major complications were recorded. Overall mortality (OM) was 32.2% (28 patients); the cancer-specific mortality was 13.8%. Conclusions: Adjuvant bacillus Calmette-Guérin significantly reduces the risk of recurrence, as does switch to mTOR inhibitors. Multiple tumors increase the risk

Treatment options and predictive factors for recurrence and cancer-specific mortality in bladder cancer after renal transplantation: A multi-institutional analysis. / Opciones terapéuticas y factores predictivos de recurrencia y mortalidad cáncer-específica en pacientes con tumor vesical después de trasplante renal: análisis multiinstitucional.

OBJECTIVES: Bladder cancer (BC) in the transplanted population can represent a challenge owing to the immunosuppressed state of patients and the higher rate of comorbidities. The objective was to analyze the treatment of BC after renal transplant (RT), focusing on the mode of presentation, diagnosis, treatment options and predictive factors for recurrence. MATERIAL AND METHODS: We conducted an observational prospective study with a retrospective analysis of 88 patients with BC after RT at 10 European centers. Clinical and oncologic data were collected, and indications and results of adjuvant treatment reviewed. The Kaplan-Meier method and uni- and multivariate Cox regression analyses were performed. RESULTS: A total of 10,000 RTs were performed. Diagnosis of BC occurred at a median of 73 months after RT. Median follow-up was 126 months. Seventy-one patients (81.6%) had non-muscle invasive bladder cancer, of whom 29 (40.8%) received adjuvant treatment; of these, six (20.6%) received bacillus Calmette-Guérin and 20 (68.9%) mitomycin C. At univariate analysis, patients who received bacillus Calmette-Guérin had a significantly lower recurrence rate (P=.043). At multivariate analysis, a switch from immunosuppression to mTOR inhibitors significantly reduced the risk of recurrence (HR 0.24, 95% CI: 0.053-0.997, P=.049) while presence of multiple tumors increased it (HR 6.31, 95% CI: 1.78-22.3, P=.004). Globally, 26 patients (29.88%) underwent cystectomy. No major complications were recorded. Overall mortality (OM) was 32.2% (28 patients); the cancer-specific mortality was 13.8%. CONCLUSIONS: Adjuvant bacillus Calmette-Guérin significantly reduces the risk of recurrence, as does switch to mTOR inhibitors. Multiple tumors increase the risk.

Elevated CYP2C19 expression is associated with depressive symptoms and hippocampal homeostasis impairment.

This corrects the article DOI: 10.1038/mp.2016.204.

Elevated CYP2C19 expression is associated with depressive symptoms and hippocampal homeostasis impairment.

The polymorphic CYP2C19 enzyme metabolizes psychoactive compounds and is expressed in the adult liver and fetal brain. Previously, we demonstrated that the absence of CYP2C19 is associated with lower levels of depressive symptoms in 1472 Swedes. Conversely, transgenic mice carrying the human CYP2C19 gene (2C19TG) have shown an anxious phenotype and decrease in hippocampal volume and adult neurogenesis. The aims of this study were to: (1) examine whether the 2C19TG findings could be translated to humans, (2) evaluate the usefulness of the 2C19TG strain as a tool for preclinical screening of new antidepressants and (3) provide an insight into the molecular underpinnings of the 2C19TG phenotype. In humans, we found that the absence of CYP2C19 was associated with a bilateral hippocampal volume increase in two independent healthy cohorts (N=386 and 1032) and a lower prevalence of major depressive disorder and depression severity in African-Americans (N=3848). Moreover, genetically determined high CYP2C19 enzymatic capacity was associated with higher suicidality in depressed suicide attempters (N=209). 2C19TG mice showed high stress sensitivity, impaired hippocampal Bdnf homeostasis in stress, and more despair-like behavior in the forced swim test (FST). After the treatment with citalopram and 5-HT1A receptor agonist 8OH-DPAT, the reduction in immobility time in the FST was more pronounced in 2C19TG mice compared with WTs. Conversely, in the 2C19TG hippocampus, metabolic turnover of serotonin was reduced, whereas ERK1/2 and GSK3ß phosphorylation was increased. Altogether, this study indicates that elevated CYP2C19 expression is associated with depressive symptoms, reduced hippocampal volume and impairment of hippocampal serotonin and BDNF homeostasis.

High frequency of CYP2D6 ultrarapid metabolizer genotypes in an Ashkenazi Jewish population from Argentina.

A twofold higher frequency of CYP2D6 ultrarapid metabolizers (estimated from genotype: gUMs) was reported among Ashkenazi Jews (AJ) living in New York (USA) than in other North American Caucasians, which might be important to guide the prescription for CYP2D6 substrates in AJ communities around the world. This study was aimed to determine whether the high frequency of CYP2D6 gUMs described in AJ from USA was replicated in AJ from Argentina when compared with other multiethnic admixture Argentines (GA). The frequency of the most common allelic variants and of CYP2D6 gUMs (>2 active genes) and poor metabolizers (0 active genes, gPMs) was also compared among the studied Argentine populations. CYP2D6 genotyping was performed in 173 AJ and 246 GA DNA samples of unrelated donors from the metropolitan area of Buenos Aires. CYP2D6 alleles (*2, *3, *4, *5, *6, *10, *17, *35, *41 and multiple copies), genotypes and functional phenotype frequencies were determined. The frequencies of gUMs and gPMs in AJ from Argentina were 11.5% and 5.2%, respectively, whereas in GA, the frequencies of gUM and gPMs were 6.5% and 4.9%, respectively. Comparisons between AJ and GA showed that gUMs frequencies were twofold higher (P<0.05) in AJ than GA. CYP2D6*35 allele was more frequent in GA than AJ, whereas CYP2D6*41 and *1xN were more frequent in AJ than in GA (P<0.05). This study supports the previously reported high frequency of gUMs on another Ashkenazi population in New York. The present findings also support the interethnic variability of CYP2D6 genetic polymorphism in the overall Argentine population.

High frequency of CYP2D6 ultrarapid metabolizers in Spain: controversy about their misclassification in worldwide population studies.

A high frequency (7-10%) of CYP2D6 ultrarapid metabolizers estimated from the genotype (gUMs) has been claimed to exist among Spaniards and Southern Europeans. However, methodological aspects such as the inclusion of individuals carrying non-active multiplied alleles as gUMs may have led to an overestimation. Thus, this study aimed to analyze the gUM frequency (considering only those carrying more than two active genes) in 805 Spanish healthy volunteers studied for CYP2D6*2, *3, *4, *5, *6, *10, *17, *35, *41, and multiplications. Second, all worldwide studies reporting gUM frequencies were reviewed in order to evaluate potential misclassifications. The gUM frequency in this Spanish population was 5.34%, but increased to 8.3% if all individuals with CYP2D6 multiplications were classified as gUMs without considering the activity of the multiplied alleles. Moreover, among all reviewed worldwide studies only 55.6% precisely determined whether the multiplied alleles were active. Present results suggest that the evaluation of CYP2D6 ultrarapid metabolism should be standarized, and that the frequency of gUMs should be reconsidered in Spaniards and globally.

Interethnic variation of CYP2C19 alleles, 'predicted' phenotypes and 'measured' metabolic phenotypes across world populations.

The present study evaluates the worldwide frequency distribution of CYP2C19 alleles and CYP2C19 metabolic phenotypes ('predicted' from genotypes and 'measured' with a probe drug) among healthy volunteers from different ethnic groups and geographic regions, as well as the relationship between the 'predicted' and 'measured' CYP2C19 metabolic phenotypes. A total of 52 181 healthy volunteers were studied within 138 selected original research papers. CYP2C19*17 was 42- and 24-fold more frequent in Mediterranean-South Europeans and Middle Easterns than in East Asians (P<0.001, in both cases). Contrarily, CYP2C19*2 and CYP2C19*3 alleles were more frequent in East Asians (30.26% and 6.89%, respectively), and even a twofold higher frequency of these alleles was found in Native populations from Oceania (61.30% and 14.42%, respectively; P<0.001, in all cases), which may be a consequence of genetic drift process in the Pacific Islands. Regarding CYP2C19 metabolic phenotype, poor metabolizers (PMs) were more frequent among Asians than in Europeans, contrarily to the phenomenon reported for CYP2D6. A correlation has been found between the frequencies of CYP2C19 poor metabolism 'predicted' from CYP2C19 genotypes (gPMs) and the poor metabolic phenotype 'measured' with a probe drug (mPMs) when subjects are either classified by ethnicity (r=0.94, P<0.001) or geographic region (r=0.99, P=0.002). Nevertheless, further research is needed in African and Asian populations, which are under-represented, and additional CYP2C19 variants and the 'measured' phenotype should be studied.

CYP2C9, CYP2C19, ABCB1 genetic polymorphisms and phenytoin plasma concentrations in Mexican-Mestizo patients with epilepsy.

We aimed to explore the possible influence of CYP2C9 (*2, *3 and IVS8-109 A>T), CYP2C19 (*2, *3 and *17) and ABCB1 (1236C>T, 2677G>A/T and 3435C>T) on phenytoin (PHT) plasma concentrations in 64 Mexican Mestizo (MM) patients with epilepsy currently treated with PHT in mono- (n=25) and polytherapy (n=39). Genotype and allele frequencies of these variants were also estimated in 300 MM healthy volunteers. Linear regression models were used to assess associations between the dependent variables (PHT plasma concentration and dose-corrected PHT concentration) with independent variables (CYP2C9, CYP2C19 and ABCB1 genotypes, ABCB1 haplotypes, age, sex, weight, and polytherapy). In multivariate models, CYP2C9 IVS8-109 T was significantly associated with higher PHT plasma concentrations (t(64)=2.27; P=0.03). Moreover, this allele was more frequent in the supratherapeutic group as compared with the subtherapeutic group (0.13 versus 0.03, respectively; P=0.05, Fisher's exact test). Results suggest that CYP2C9 IVS8-109 T allele may decrease CYP2C9 enzymatic activity on PHT. More research is needed to confirm findings.

ABCB1 gene polymorphisms and violent suicide attempt among survivors.

INTRODUCTION: Those suicide attempters that choose violent methods dramatically diminish the possibility of survival. Completed suicide using violent means, which is common among first-time suicide attempters, was recently found to be more likely among T allele carriers in the three most common ABCB1 SNPs, encoding for P-gp. Thus, this study examined, for the first time, whether these ABCB1 SNPs were associated with the use of violent means among survivors of a suicide attempt. MATERIAL AND METHODS: Suicide attempters (n = 578, 87.4% women; of whom 16.6% committed a violent intent) were genotyped for exonic SNPs in the ABCB1 (C1236T, G2677T/A, C3435T). The relations of the three genotypes and of the TTT haplotype with the use of a violent suicide method were evaluated separately. The impact of confounds on these variables was controlled. RESULTS: A higher frequency (p = 0.02) of suicide attempters using violent methods was found among those carrying the ABCB1 haplotype (1236TT-2677TT-3435TT). Since gender and number of previous suicide attempts were identified as confounds, the relation was tested in the subset of women who were first-time attempters or second- and more-time attempters. The ABCB1 haplotype increased the risk more than three times in those women attempting a violent suicide for the first time (OR = 3.6; CI95%: 1.08-12.09; p = 0.04). DISCUSSION: The ABCB1 haplotype (1236TT-2677TT-3435TT) was related to the use of a violent suicide attempt method. Genotyping for these three ABCB1 SNPs may be helpful to detect people at risk of first suicide intents using violent methods.

A combined high CYP2D6-CYP2C19 metabolic capacity is associated with the severity of suicide attempt as measured by objective circumstances.

This study examined, for the first time, whether a high CYP2D6-CYP2C19 metabolic capacity combination increases the likelihood of suicidal intent severity in a large study cohort. Survivors of a suicide attempt (n=587; 86.8% women) were genotyped for CYP2C19 (*2, *17) and CYP2D6 (*3, *4, *4xN, *5, *6, *10, wtxN) genetic variation and evaluated with the Beck Suicide Intent Scale (SIS). Patients with a high CYP2D6-CYP2C19 metabolic capacity showed an increased risk for a severe suicide attempt (P<0.01) as measured by the SIS-objective circumstance subscale (odds ratio (OR)=1.37; 95% confidence interval (CI)=1.05-1.78; P=0.02) after adjusting for confounders (gender, age, level of studies, marital status, mental disorders, tobacco use, family history of suicide, personal history of attempts and violence of the attempt). Importantly, the risk was greater in those without a family history of suicide (OR=1.82; CI=1.19-2.77; P=0.002). Further research is warranted to evaluate whether the observed relationship is mediated by the role of CYP2D6 and CYP2C19 involvement in the endogenous physiology or drug metabolism or both.

Utilidad de la calprotectina fecal en la enfermedad celiaca pediátrica / Usefulness of the faecal calprotectin on the pediatric coeliac disease

Introducción: El objetivo del presente estudio es analizar el comportamiento de la calprotectina fecal en los pacientes pediátricos con enfermedad celiaca, comparando sus niveles mientras recibían dieta con y sin gluten. También se han incluido en la comparación pacientes sanos y con diversas patologías digestivas no inflamatorias. Material y métodos: Se han recogido muestras de heces de pacientes celiacos con diagnóstico de novo (con gluten) y pacientes en seguimiento (sin gluten). Se incluyeron en el grupo control niños sanos sin patología digestiva y otros con diversos trastornos digestivos no diagnosticados de enfermedad inflamatoria intestinal. Resultados: La calprotectina fecal fue significativamente más alta en los pacientes celiacos que recibieron una dieta con gluten (119,2 ± 122,6 µg/g) que en los que recibieron una dieta sin gluten (21,5 ± 24,7 µg/g). Estos últimos presentaron valores similares al grupo control sano. Conclusiones: La calprotectina fecal está elevada en los pacientes celiacos con ingesta de gluten respecto a los celiacos con dieta sin gluten y los pacientes sanos. Este marcador podría usarse para la detección precoz de la ingesta de gluten (AU)

Introduction: The objective of the present research is to study the behavior of the faecal calprotectin in the pediatric coeliac disease, comparing its levels while receiving a diet with and without gluten. For the comparison, there were also included healthy children, and patients with diverse non-inflammatory digestive pathologies. Materials and methods: There have been collected stool samples from de novo coeliac patients (with gluten) and from follow-up coeliac patients (without gluten). As control groups, there were included healthy children without any digestive pathology and others with diverse digestive non-diagnosed disorders from the inflammatory bowel disease. Results: The faecal calprotectin was significantly higher in the coeliac patients with gluten (119.2 ± 122.6 µg/g) than in the patients with the gluten-free diet (21.5 ± 24.7 µg/g). The later showed similar values to those in the healthy control group. Conclusions: The faecal calprotectin is higher in the coeliac patients with gluten ingestion than in the coeliac patients with the gluten-free diet and in the healthy group. This could be used as a marker for early detection of gluten ingestion (AU)

Interethnic differences in the relevance of CYP2C9 genotype and environmental factors for diclofenac metabolism in Hispanics from Cuba and Spain.

The aims of this study were to evaluate the diclofenac metabolism in Hispanics from Cuba and Spain and its relation to ethnicity, CYP2C9 genotypes and environmental factors. Diclofenac hydroxylation capacity (concentration ratios of diclofenac/metabolites in 8-h urine) was studied in 160 Cuban (classified as 76 Cuban-Whites-CWs and 84 Cuban-Mestizos-CMs) and 148 Spaniard (SPs) healthy volunteers. Diclofenac and its main metabolites, 4'-hydroxy (OH), 3'-OH and 5-OH diclofenac, and CYP2C9*2 to *6 and *8 alleles were also determined in 132 and 128 CWs and CMs, respectively. Gender, tobacco, caffeine and ethanol consumption were also evaluated. The mean diclofenac/4'-OH diclofenac ratio was higher in CMs (0.72±0.25) than in CWs (0.64±0.20; P<0.05) and SPs (0.57±0.26; P<0.001). The mean diclofenac/4'-OH diclofenac ratio was higher (P<0.05) in subjects with CYP2C9*1/*3 (0.77±0.19; n=22) and CYP2C9*1/*8 (0.93±0.33; n=4) genotypes than with CYP2C9*1/*1 (0.65±0.24; n=90). Environmental factors did not seem to influence the diclofenac metabolism in these populations. The present findings show for the first time interethnic differences between Hispanic groups in urinary diclofenac/4'-OH diclofenac ratios, and the relevance of CYP2C9*3 and CYP2C9*8 alleles.

Aproximación histórica al tratamiento quirúrgico de la disfunción eréctil / Historical Approach to the Surgical Treatment of Erectile Dysfunction

Introducción: A través de la historia de la humanidad la disfunción eréctil ha supuesto uno de los problemas de salud más continuamente presentes. Como consecuencia se produjo una búsqueda de soluciones que, una tras otra, se demostraban como infructuosas. En este contexto la aparición de posibles cirugías a principios del siglo XX supuso una revolución que, aun así, tardaría varias décadas en demostrarse efectiva. Adquisición de evidencia: Se realiza una revisión bibliográfica que muestra el proceso en el desarrollo de posibles tratamientos quirúrgicos de recuperación hormonal para la disfunción eréctil, posteriormente, la irrupción de la cirugía vascular, con nuevas técnicas de anastomosis y, más adelante, el desarrollo de los implantes de prótesis peneanas como alternativa terapéutica. Síntesis de evidencia: La publicación de resultados obtenidos con la cirugía para la disfunción eréctil ha carecido durante décadas de falta de objetivación, al ser la función sexual un tema restringido a la privacidad de los pacientes. Esta situación ha llevado a una confianza sobre los resultados referidos por varios autores sin poderse constatar su auténtica credibilidad, demostrándose posteriormente que algunos de estos logros no eran reproducibles. Conclusiones: En el presente artículo se recuerdan algunos de los hitos más importantes en el avance de las cirugías diseñadas para tratar la disfunción eréctil. Los logros conseguidos, y también los aparentes fracasos, ofrecen un motivo de reflexión sobre cómo se ha avanzado hasta el momento presente y cómo se puede avanzar en un futuro cercano (AU)

Introduction: Throughout human history, erectile dysfunction has represented one of the most omnipresent health problems. This has resulted in a search for solutions that, one after the other, have been shown to be fruitless. In this context, the emergence of possible surgical solutions at the start of the 20th century represented a revolution that, even then, would take several decades to demonstrate their effectiveness. Acquisition of evidence: We performed a literature review that shows the process in the development of potential surgical treatments for hormonal restoration for erectile dysfunction, followed by the sudden emergence of vascular surgery, with new anastomosis techniques, and in the future, the development of penile prosthetic implants as alternative treatments. Summary of the evidence: The publication of results from erectile dysfunction surgery has been lagging for decades due to a lack of objectivity, given that sexual function is a topic restricted by patients’ privacy. This situation has led to a reliance on results reported by various authors whose actual credibility could not be verified, with subsequent demonstrations showing that some of these results were not reproducible. Conclusions: This article reviews some of the most important milestones in the progress of surgeries designed to treat erectile dysfunction. The achievements and apparent failures provide a reason for reflection on how we far we have come and how far we can go in the near future(AU)

Tratamiento del cáncer de próstata y cáncer renal con fármacos orales (abiraterona y antiangiogénicos): posicionamiento de la Asociación Española de Urología / Treatment of prostate and renal cancer with oral drugs (abiratarone and antiangiogenic agents): Positioning statement from the Spanish Association of Urology

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Historical approach to the surgical treatment of erectile dysfunction.

INTRODUCTION: Throughout human history, erectile dysfunction has represented one of the most omnipresent health problems. This has resulted in a search for solutions that, one after the other, have been shown to be fruitless. In this context, the emergence of possible surgical solutions at the start of the 20th century represented a revolution that, even then, would take several decades to demonstrate their effectiveness. ACQUISITION OF EVIDENCE: We performed a literature review that shows the process in the development of potential surgical treatments for hormonal restoration for erectile dysfunction, followed by the sudden emergence of vascular surgery, with new anastomosis techniques, and in the future, the development of penile prosthetic implants as alternative treatments. SUMMARY OF THE EVIDENCE: The publication of results from erectile dysfunction surgery has been lagging for decades due to a lack of objectivity, given that sexual function is a topic restricted by patients' privacy. This situation has led to a reliance on results reported by various authors whose actual credibility could not be verified, with subsequent demonstrations showing that some of these results were not reproducible. CONCLUSIONS: This article reviews some of the most important milestones in the progress of surgeries designed to treat erectile dysfunction. The achievements and apparent failures provide a reason for reflection on how we far we have come and how far we can go in the near future.

Neurological toxicity after phenytoin infusion in a pediatric patient with epilepsy: influence of CYP2C9, CYP2C19 and ABCB1 genetic polymorphisms.

Pharmacogenetic studies have shown that genetic defects in drug-metabolizing enzymes encoded by CYP2C9, CYP2C19 genes and by the transporter ABCB1 gene can influence phenytoin (PTH) plasma levels and toxicity. The patient reported here is a 2-year-old girl with a medical history of cryptogenic (probably symptomatic) epilepsy, who had her first focal seizure with secondary generalization at 13 months of age. She initially received oral valproate treatment and three months later, she was prescribed an oral oxcarbazepine treatment. At 20 months of age, she was admitted to the Emergency Department because of generalized convulsive Status Epilepticus needing to be immediately treated with rectal diazepam (0.5 mg kg(-1)), intravenous diazepam (0.3 mg kg(-1)), and intravenous phenytoin with an initial-loading dose of 15 mg kg(-1). However, two hours after the initial-loading dose of PTH, the patient developed dizziness, nystagmus, ataxia and excessive sedation. Other potential causes of PTH toxicity were excluded such as drug interactions, decreased albumin or lab error. Therefore, to explain the neurological toxicity, PTH plasma levels and CYP2C9, CYP2C19 and ABCB1 genetic polymorphisms were analyzed. Initial plasma PTH levels were higher than expected (69 mg l(-1); normal range: 10-20 mg l(-1)), and the patient was homozygous for the CYP2C9*2 allele, heterozygous for the CYP2C19*4 allele and homozygous for the 3435C and 1236C ABCB1 alleles. Present findings support the previously established relationship between CYP2C9 and CYP2C19 genetic polymorphisms and the increased risk to develop PTH toxicity owing to high plasma concentrations. Nevertheless, although the association of these genes with PTH-induced adverse effects has been well-documented in adult populations, this is the first report examining the influence of these genetic polymorphisms on PTH plasma levels and toxicity in a pediatric patient.