Perceived quality of life in patients with psoriasis treated with interleukin 17 or 23 inhibitors.

OBJECTIVE: To determine the effectiveness in terms of quality of life perceived by adult patients with moderate/severe plaque psoriasis treated with interleukin 17 or 23 inhibitors and to identify associated factors. METHOD: Cross-sectional observational study including adult patients diagnosed with moderate/severe plaque psoriasis treated with interleukin 17 or 23 inhibitors for at least 12 or 16 weeks in follow-up, respectively. RESULTS: Forty-one patients were included: 65% male, median age 54 years (SD=13). The included patients were treated with ixekizumab 35%, guselkumab 25%, secukinumab 17.5%, brodalumab 15%, and risankizumab 7.5%. Psoariasis area severity index (PASI) reduction was 94.6% (RIC 76.8-100%), DLQI of 1 (RIC 0-2.75), DLQI≤1 60%. The most affected health dimensions were symptoms and perceptions (57.5%), activities of daily living (27.5%), and discomfort caused with treatment (17.5%). No association was found between DLQI score <1 and demographic, comorbidities, and treatment-related variables. The median PASI reduction in patients with DLQI<1 was superior to patients with DLQI>1 (100% vs 90.2%, p=.025). CONCLUSIONS: Patients with moderate/severe plaque psoriasis treated with interleukin 17 or 23 inhibitors achieve adequate therapeutic targets achieving the target set according to clinical practice guideline recommendations (score ≤1 on the DLQI questionnaire and 90-100% reduction in the PASI index) and in accordance with the results of recent meta-analyses and real-life studies. A greater reduction of the PASI index is observed in the group reaching the quality of life target, there being the possibility of using patient-reported outcomes in the evaluation of treatment effectiveness.

Invasive meningococcal disease in older adults: current perspectives and call for action.

PURPOSE: Invasive meningococcal disease (IMD) is a devastating condition. While most attention is directed towards disease in children and adolescents, IMD poses an important cause of morbidity and mortality in adults ≥60 years. While immunization is a critical component of healthy ageing strategies, meningococcal immunization is not routinely offered to older adults. The aim of this review was to summarize clinical and epidemiological aspects of IMD and available immunization strategies, with a particular focus on disease in older individuals, to emphasize the importance of this rather neglected area. METHODS: An expert working group was established to evaluate clinical and epidemiological data to raise awareness of IMD in older individuals, and develop suggestions to improve the existing burden. RESULTS: Routine child and adolescent meningococcal immunization has substantially reduced IMD in these targeted populations. Consequently, prevalence and proportion of IMD among those ≥60 years, mostly unvaccinated, is increasing in developed countries (accounting for up to 25% of cases). IMD-related mortality is highest in this age-group, with substantial sequelae in survivors. IMD due to serogroups W and Y is more prevalent among older adults, often with atypical clinical features (pneumonia, gastrointestinal presentations) which may delay timely treatment. CONCLUSIONS: IMD in older adults remains overlooked and greater awareness is required at clinical and societal levels. We encourage clinicians and immunization policy makers to reconsider IMD, with a call for action to remedy existing inequity in older adult access to protective meningococcal immunization.

Perceived quality of life in patients with psoriasis treated with interleukin 17 and 23 inhibitors. / Calidad de vida percibida por los pacientes con psoriasis tratados con inhibidores de interleucina 17 y 23.

OBJECTIVE: To determine the effectiveness in terms of quality of life perceived by adult patients with moderate/severe plaque psoriasis treated with interleukin 17 or 23 inhibitors and to identify associated factors. METHOD: Cross-sectional observational study including adult patients diagnosed with moderate/severe plaque psoriasis treated with interleukin 17 or 23 inhibitors for at least 12 or 16 weeks in follow-up, respectively. RESULTS: Forty-one patients were included: 65% male, median age 54 years (SD=13). The included patients were treated with ixekizumab 35%, guselkumab 25%, secukinumab 17.5%, brodalumab 15% and risankizumab 7.5%. Psoariasis area severity index (PASI) reduction was 94.6% (RIC 76.8-100%), DLQI of 1 (RIC 0-2.75), DLQI ≤ 1, 60%. The most affected health dimensions were symptoms and perceptions (57.5%), activities of daily living (27.5%) and discomfort caused with treatment (17.5%). No association was found between DLQI score < 1 and demographic, comorbidities and treatment-related variables. The median PASI reduction in patients with DLQI<1 was superior to patients with DLQI > 1 (100% vs 90.2%, p=0.025). CONCLUSIONS: Patients with moderate/severe plaque psoriasis treated with interleukin 17 or 23 inhibitors achieve adequate therapeutic targets achieving the target set according to clinical practice guideline recommendations (score ≤1 on the DLQI questionnaire and 90-100% reduction in the PASI index) and in accordance with the results of recent meta-analyses and real-life studies. A greater reduction of the PASI index is observed in the group reaching the quality of life target, there being the possibility of using patient-reported outcomes in the evaluation of treatment effectiveness.

Pandemic's influence on parents' attitudes and behaviors toward meningococcal vaccination.

Invasive meningococcal disease is a life-threatening infection preventable through vaccination. Pediatric vaccination rates have declined during the coronavirus disease 2019 (COVID-19) pandemic. This survey aimed to understand how parents' attitudes and behaviors have changed during the pandemic with regard to immunization and, more specifically, meningococcal vaccination. An online survey was emailed to parents of eligible children 0-4 years, following the selection process from UK, France, Germany, Italy, Brazil, Argentina, and Australia; and of adolescents 11-18 years from US. Data collection took place 19 January-16 February 2021. Quotas were set to ensure a representative sample. Eleven questions relating to general perceptions around vaccination and attitudes and behaviors toward meningitis vaccination were displayed. On 4,962 parents (average 35 years) participating in the survey, most (83%) believed important for their child to continue receiving recommended vaccines during the COVID-19 pandemic. Nearly half of routine vaccine appointments were delayed or canceled due to the pandemic, and 61% of respondents were likely to have their children catch up once COVID-19 restrictions were lifted. 30% of meningitidis vaccination appointments were canceled or delayed during the pandemic, and 21% of parents did not intend to reschedule them because of lockdown/stay at home regulations, and fear of catching COVID-19 in public places. It is crucial to communicate clear instructions to health workers and the general population and to provide appropriate safety precautions in vaccination centers. This will help to maintain vaccination rates and limit infections to prevent future outbreaks.

What is the context? Invasive meningococcal disease (IMD) is an uncommon infection that can lead to permanent disabilities and even death.Meningitis vaccination can prevent IMDs caused by Neisseria meningitidis.Vaccination rates have declined during the coronavirus (COVID-19) pandemic.What is new? We collected opinion of parents from the UK, France, Germany, Italy, Brazil, Argentina, Australia, and the US, to understand their attitudes and behaviors toward meningitis vaccination during the COVID-19 pandemic.Results were reviewed by health care professional experts as well as by patient authors (IMD survivors).Most (83%) of the 4,962 parents believed that it is important for their child to continue receiving recommended vaccines during the COVID-19 pandemic.Half of the scheduled appointments for meningitis vaccination were canceled or delayed during the COVID-19 pandemic, mainly due to lockdown regulations and fear of catching COVID-19.Twenty-one percent of the parents who had their child's meningitis vaccination appointment canceled, did not intend to reschedule it.What is the impact? It is crucial that clear information is communicated by health care authorities and practitioners about the availability of vaccination during pandemic and the safety precautions that are taken.Collected opinions emphasize the importance of continuing vaccinations against infectious diseases during a pandemic.

Evidence-based Medicine: Perceptions, Attitudes, and Skills Among European Urology Residents.

Background: Evidence-based medicine (EBM) was introduced as a concept in the early 1990s as an integration of the best available evidence with clinical expertise and patient values. Objective: To evaluate the current status of EBM training and EBM perception, attitudes, and self-perceived skills among European urology residents. Design setting and participants: Our online open survey comprised 28 multiple-choice items, including ten questions with responses on a five-point Likert scale ranging from 1 = strongly disagree to 5 = strongly agree. The survey was distributed via the mailing lists and social media accounts of the European Society of Residents in Urology, German Society of Residents in Urology, French Society of Urologists in Training, Spanish Urology Residents Working Group, Italian Society of Residents in Urology, and the Urology Social Media Working Group in two rounds (May-July 2019 and July 2020). We excluded responses from non-European countries. Outcome measurements and statistical analysis: The online open survey comprised 28 multiple-choice items. These included ten questions with answers on a five-point Likert scale with response items ranging from strongly disagree (score of 1) to strongly agree (score of 5). Results and limitations: We received 210 responses, of which 181 from 23 European countries were eligible. Approximately three-quarters (73.7%) of the respondents were male, with a mean age of 31 yr. Only 28.2% reported EBM training as part of their urology curriculum and 19.3% felt that the training they received was sufficient to guide their daily practice. An overwhelming majority (91.5%) stated that they would be interested in more formalized EBM training or additional training. There was a strong level of agreement (median score 5, interquartile range 4-5) that EBM is important for daily medical and surgical practice and that it improves patient care. Overall, the mean self-perceived understanding of basic EBM concepts was good. Limitations include concerns about generalizability given its internet-based format, the inability to calculate a response rate, poor representation from some European regions, and limited sample size. Conclusions: Our survey suggests that European urology residents receive a limited amount of EBM training despite considerable appreciation, interest, and self-perceived deficits for more advanced concepts. Formal integration of EBM teaching in all European residency programs should be considered. Patient summary: We performed an online survey of urology residents in Europe. We found that residents have positive perceptions of and attitudes to evidence-based medicine but most programs lack formal training in this area.

[Bladder paraganglioma: Report of two cases and a literature review.] / Paraganglioma vesical: reporte de dos casos clínicos y revisión de la literatura.

OBJECTIVE: Description of two incidental cases of bladder paraganglioma in women and review of the published literature. METHODS: A bibliographic search was carried out in Medline over the last 10 years according to the terms "urinary bladder" and "paraganglioma". RESULTS: Bladder paraganglioma (BP) accounts for less than 0.06% of bladder tumors and 10% of all paragangliomas. It may be sporadic or associated with hereditary predisposition syndromes such as Hereditary Paraganglioma- Pheochromocytoma Syndrome. Due to its rarity, there are no recommendations for treatment and monitoring but, their risk of malignancy forces a long-term follow up. The study of germinal mutations through massive sequencing ruled out the association with a hereditary syndrome. Initial management included early reassessment by cystoscopy, transurethral bladder resection (TURB) and imaging. CONCLUSIONS: Bladder paragangliomas are rare tumors that can be associated to hereditary syndromes. Its treatment and follow - up must be based on a multidisciplinary approach.

OBJETIVO: Descripción de dos casos incidentales de paraganglioma vesical en mujeres y revisión de la literatura publicada.MÉTODOS: Se realizó una búsqueda bibliográfica en Medline en los últimos 10 años según los términos "urinary bladder" y "paraganglioma". RESULTADOS: El paraganglioma vesical representa menos del 0,06% de los tumores vesicales y el 10% de todos los paragangliomas. Suelen ser esporádicos, pudiendo también asociarse a síndromes de predisposición hereditaria como el síndrome de paraganglioma ­ feocromocitoma hereditario. Dada su baja frecuencia, no existen pautas de manejo. Su riesgo de malignización obliga a un seguimiento a largo plazo.  El estudio de mutaciones germinales mediante secuenciación masiva descartó la asociación a un síndrome hereditario. El manejo inicial incluyó reevaluación temprana mediante cistoscopia, resección transuretral vesical (RTU ­ V) e imagen. CONCLUSIONES: Los paragangliomas vesicales son neoplasias infrecuentes que pueden asociarse a síndromes hereditarios. Su tratamiento y seguimiento deberían basarse en un enfoque multidisciplinar.

Paraganglioma vesical. Reporte de dos casos clínicos y revisión de la literatura / Bladder paraganglioma. Report of two clinical cases and review of the literature

Objetivos: Descripción de dos casos incidentales de paraganglioma vesical en mujeres y revisiónde la literatura publicada. Métodos: Se realizó una búsqueda bibliográfica en Medline en los últimos 10 años según los términos “urinary bladder” y “paraganglioma”. Resultados: El paraganglioma vesical representa menos del 0,06% de los tumores vesicales y el 10% de todos los paragangliomas. Suelen ser esporádicos, pudiendo también asociarse a síndromes de predisposición hereditaria como el síndrome de paraganglioma – feocromocitoma hereditario. Dada su baja frecuencia, no existen pautas de manejo. Su riesgo de malignización obliga a un seguimiento a largo plazo. El estudio de mutaciones germinales mediante secuenciación masiva descartó la asociación a un síndrome hereditario. El manejo inicial incluyó reevaluación temprana mediante cistoscopia, resección transuretral vesical (RTU – V) e imagen. Conclusiones: Los paragangliomas vesicales son neoplasias infrecuentes que pueden asociarse a síndromes hereditarios. Su tratamiento y seguimiento deberían basarse en un enfoque multidisciplinar.(AU)

Objetives: Description of two incidental cases of bladder paraganglioma in women and review of the published literature. Methods: A bibliographic search was carried out in Medline over the last 10 years according to the terms “urinary bladder” and “paraganglioma”. Results: Bladder paraganglioma (BP) accounts for less than 0.06% of bladder tumors and 10% of all paragangliomas. It may be sporadic or associated with hereditary predisposition syndromes such as Hereditary Paraganglioma-Pheochromocytoma Syndrome. Due to its rarity, there are no recommendations for treatment and monitoring but, their risk of malignancy forces a long-term follow up. The study of germinal mutations through massive sequencing ruled out the association with a hereditary syndrome. Initial management included early reassessment by cystoscopy, transurethral bladder resection (TURB) and imaging. Conclusiones: Bladder paragangliomas are rare tumors that can be associated to hereditary syndromes. Itstreatment and follow – up must be based on a multidisciplinary approach.(AU)

Impact of COVID-19 in spanish urology residents: Recommendations and perspective. / El impacto del COVID-19 en la residencia en urología en España: perspectivas y recomendaciones.

The COVID-19 pandemic has seriously disrupted the day-to-day running of hospitals, affecting the activity of all medical and surgical departments. It has also affected urology residents, depriving them of training at their usual workplaces and forcing them to support COVID units. This has implied not only the loss of daily activities, but also the uncertainty of job opportunities for the final year residents. In addition, the cancellation of numerous events such as congresses, exams,or courses has affected the annual planning of the specialty. A review of the current literature on the impact of the COVID-19 pandemic, as well as the de-escalation process, on resident training has been carried out using web search and PubMed. The situation of the residents has been analyzed, both through the information generated by recent literature and by the personal experience of the authors, from different areas: evaluation systems, educational and surgical aspects, as well as healthcare work. As a result of this review, the negative impact of the crisison urology resident training can be observed, especially in the surgical field, but new learning opportunities or new forms of communication with the patient can also be observed. These educational and healthcare resources invite the urology resident in particular, and the medical society in general, to reinvent themselves. The aim of this article is to analyse the training of the urology resident in the de-escalation phase. Similarly, the emerging educational resources during the pandemic are synthesized, inviting the reader, and especially the urology resident, to continue their training and learningin these times of uncertainty.

La pandemia por COVID-19 ha irrumpido gravemente en el día a día de los hospitales, afectando a la actividad de todos los servicios médicos y quirúrgicos. Del mismo modo ha afectado a los residentes de urología, privándoles a los mismos de seguir la formación en sus puestos de trabajo habituales y viéndose obligados a dar apoyo a las unidades COVID. Esto ha implicado, no solamente la pérdida de las actividades diarias, si no también la incertidumbre en oportunidades laborales de los residentes de último año. Además, la cancelación de numerosos eventos como congresos, exámenes o cursos, ha afectado a la planificación anual de la especialidad. Se ha realizado una revisión de la literatura actual sobre el impacto de la pandemia por COVID-19, así como el proceso de desescalada, en la formación de los residentes mediante búsqueda web y en PubMed. Se ha analizado la situación de los residentes, tanto através de la información generada por la reciente literatura, como por la experiencia personal de los autores, desde distintos ámbitos: sistemas de evaluación, aspectos docentes y quirúrgicos, así como labor asistencial. Como resultado de esta revisión, se observa el impacto negativo de la crisis en la formación del residente en urología, especialmente, en el ámbito quirúrgico, pero también se observan nuevas oportunidades de aprendizaje o formas de comunicación con el paciente. Estos recursos educativos y asistenciales invitan al residente de urología en concreto, y a la sociedad médica en general, a reinventarse. El objetivo del presente artículo es analizar la formación del residente en urología en la fase de desescalada. Del mismo modo, se sintetizan los recursos educativos emergentes durante la pandemia, invitando al lector y, de manera especial al residente de urología, a continuar su formación y aprendizaje ante estos tiempos de incertidumbre.

El impacto del COVID-19 en la residencia en urología en España: perspectivas y recomendaciones / No disponible

La pandemia por COVID-19 ha irrumpido gravemente en el día a día de los hospitales, afectando a la actividad de todos los servicios médicos y quirúrgicos. Del mismo modo ha afectado a los residentes de urología, privándoles a los mismos de seguir la formación en sus puestos de trabajo habituales y viéndose obligados a dar apoyo a las unidades COVID. Esto ha implicado, no solamente la pérdida de las actividades diarias, si no también la incertidumbre en oportunidades laborales de los residentes de último año. Además, la cancelación de numerosos eventos como congresos, exámenes o cursos, ha afectado a la planificación anual de la especialidad. Se ha realizado una revisión de la literatura actual sobre el impacto de la pandemia por COVID-19, así como el proceso de desescalada, en la formación de los residentes mediante búsqueda web y en PubMed. Se ha analizado la situación de los residentes, tanto a través de la información generada por la reciente literatura, como por la experiencia personal de los autores, desde distintos ámbitos: sistemas de evaluación, aspectos docentes y quirúrgicos, así como labor asistencial. Como resultado de esta revisión, se observa el impacto negativo de la crisis en la formación del residente en urología, especialmente, en el ámbito quirúrgico, pero también se observan nuevas oportunidades de aprendizaje o formas de comunicación con el paciente. Estos recursos educativos y asistenciales invitan al residente de urología en concreto, y a la sociedad médica en general, a reinventarse. El objetivo del presente artículo es analizar la formación del residente en urología en la fase de desescalada. Del mismo modo, se sintetizan los recursos educativos emergentes durante la pandemia, invitando al lector y, de manera especial al residente de urología, a continuar su formación y aprendizaje ante estos tiempos de incertidumbre

The COVID-19 pandemic has seriously disrupted the day-to-day running of hospitals, affecting the activity of all medical and surgical departments. It has also affected urology residents, depriving them of training at their usual workplaces and forcing them to support COVID units. This has implied not only the loss of daily activities, but also the uncertainty of job opportunities for the final year residents. In addition, the cancellation of numerous events such as congresses, exams, or courses has affected the annual planning of the specialty. A review of the current literature on the impact of the COVID-19 pandemic, as well as the de-escalation process, on resident training has been carried out using web search and PubMed. The situation of the residents has been analyzed, both through the information generated by recent literature and by the personal experience of the authors, from different areas: evaluation systems, educational and surgical aspects, as well as healthcare work. As a result of this review, the negative impact of the crisis on urology resident training can be observed, especially in the surgical field, but new learning opportunities or new forms of communication with the patient can also be observed. These educational and healthcare resources invite the urology resident in particular, and the medical society in general, to reinvent themselves. The aim of this article is to analyse the training of the urology resident in the de-escalation phase. Similarly, the emerging educational resources during the pandemic are synthesized, inviting the reader, and especially the urology resident, to continue their training and learning in these times of uncertainty

[Technical and peri-operative differences between the transvesical and extravesical approach in laparoscopic repair of vesico-vaginal fistula.] / Diferencias técnicas y peri-operatorias entre el abordaje transvesical y extravesical en la reparación laparoscópica de la fístula vesico-vaginal.

OBJECTIVE: In the laparoscopic/robotic repair (L/R R) of Vesico-vaginal Fistulas (VVF) two types of transvesical and extravesical approaches are used.However, no direct comparisons exist between both surgical approaches Moreover, a lack of clinical guidelines is currently ongoing. Therefore, the selection of the type of approach is based on the preferences of the surgeon without considering the characteristics of each case.In order to provide recommendations for the selection of the appropriate technique for each patient, we designed a study that identifies and evaluates differences between the Transvesical and Extravesical approaches in the L/R R of the VVF. PATIENTS AND METHODS: A total of 9 patients withVVF were included. Four patients underwent transvesicaltechnique and the rest the Extravesical technique. Thevariables in each group were recorded. Surgical stepswere selected with technical differences to be analyzed(identification of the fistula, dissection of the vesico-vaginalplane, cystotomy, maneuvers of exposure and cystorrhaphy). RESULTS: Short operative times and catheterization times were recorded in the Extravesical approach. Intraoperative blood loss was minimal in both groups, the hospital stay was very similar and no peri and post-operativec omplications were reported. In all cases the fistula was resolved and there have been no recurrences in a mean follow-up of 35 months. Technically, Extravesical approach minimizes the size of the cystotomy, decreases suture time, does not require maneuvers for adequate exposure, and simplifies cystorrhaphy with respect to Transvesical technique, at the expense of requiring further dissection and having a slight difficulty in locating the fistula. Transvesical technique simplifies the locationof the fistula and allows better intravesical visualization. CONCLUSION: In the L/R R of the VVF, the Extravesicaltechnique offers technical and perioperative advantages,so it must be the technique of choice for most VVFwith indication of abdominal approach. Transvesicaltechnique should be reserved for recurrent, recurrent,inflammatory fistulas, with difficulties identifying the fistulous orifice, close to ureteric orifice and with imminent need for ureteral reimplantation.

OBJETIVO: En la reparación laparoscópica/robótica (RL/R) de las Fístulas Vesico-vaginales (FVV) se emplean dos tipos de abordajes el Transvesical y el Extravesical, sin embargo no existen comparaciones directas entre ambos abordajes ni tampoco disponemos de guías clinicas, por lo cual la selección del tipo de abordaje se basa en las preferencias del cirujano sin considerarse las características de cada caso. Con el objetivo de definir recomendaciones para la selección de la técnica apropiada para cada paciente, diseñamos un estudio que identifique y evalúe las diferencias entre los abordajes Transvesical y Extravesical en la RL/R de la FVV.PACIENTES Y MÉTODOS: Un total de 9 pacientes con FVV fueron incluídas. A cuatro pacientes se les realizó técnica Transvesical y el resto la técnica Extravesical. Se registraron las variables en cada grupo. Se seleccionaron los pasos quirúrgicos con diferencias técnicas para ser analizados (identificación de la fístula, disección del plano vesico-vaginal, cistotomía, maniobras de exposición y cistorrafia). RESULTADOS: Se registraron menores tiempos quirúrgicos y tiempos de sondaje en el abordaje Extravesical. El sangrado intraoperatorio fue mínimo en ambos grupos,la estancia hospitalaria fue muy semejante y tampoco se reportaron complicaciones peri y post-operatorias. En todos los casos se resolvió la fístula y no han habido recurrencias en una media de seguimiento superior 35 meses. Técnicamente la vía Extravesical minimiza el tamaño de la cistotomía, disminuye el tiempo de sutura,no requiere de maniobras para la exposición adecuada,y simplifica la cistorrafia con respecto a la técnica Transvesical, a expensas de requerir mayor disección y tener una discreta dificultad para localizar la fístula.La técnica Transvesical simplifica la localización de la fístula y permite mejor visualización intravesical.CONCLUSIÓN: En la RL/R de la FVV, la técnica Extravesical ofrece ventajas técnicas y perioperatorias, por lo cual debe ser la técnica de elección para la mayoría de las FVV con indicación de abordaje abdominal. La técnica Transvesical se debe reservar para fístulas recurrentes,múltiples, inflamatorias, de dificil localización del orificio fistuloso, con excesiva proximidad de los meatos y con inminente necesidad de reimplante ureteral.

Diferencias técnicas y peri-operatorias entre el abordaje transvesical y extravesical en la reparación laparoscópica de la fístula vesico-vaginal / Technical and peri-operative differences between the transvesical and extravesical approach in laparoscopic repair of vesico-vaginal fistula

OBJETIVO: En la reparación laparoscópica/robótica (RL/R) de las Fístulas Vesico-vaginales (FVV) se emplean dos tipos de abordajes el Transvesical y el Extravesical, sin embargo no existen comparaciones directas entre ambos abordajes ni tampoco disponemos de guías clinicas, por lo cual la selección del tipo de abordaje se basa en las preferencias del cirujano sin considerarse las características de cada caso. Con el objetivo de definir recomendaciones para la selección de la técnica apropiada para cada paciente, diseñamos un estudio que identifique y evalúe las diferencias entre los abordajes Transvesical y Extravesical en la RL/R de la FVV. PACIENTES Y MÉTODOS: Un total de 9 pacientes con FVV fueron incluídas. A cuatro pacientes se les realizó técnica Transvesical y el resto la técnica Extravesical. Se registraron las variables en cada grupo. Se seleccionaron los pasos quirúrgicos con diferencias técnicas para ser analizados (identificación de la fístula, disección del plano vesico-vaginal, cistotomía, maniobras de exposición y cistorrafia). RESULTADOS: Se registraron menores tiempos quirúrgicos y tiempos de sondaje en el abordaje Extravesical. El sangrado intraoperatorio fue mínimo en ambos grupos,la estancia hospitalaria fue muy semejante y tampoco se reportaron complicaciones peri y post-operatorias. En todos los casos se resolvió la fístula y no han habido recurrencias en una media de seguimiento superior 35 meses. Técnicamente la vía Extravesical minimiza el tamaño de la cistotomía, disminuye el tiempo de sutura,no requiere de maniobras para la exposición adecuada,y simplifica la cistorrafia con respecto a la técnica Transvesical, a expensas de requerir mayor disección y tener una discreta dificultad para localizar la fístula.La técnica Transvesical simplifica la localización de la fístula y permite mejor visualización intravesical. CONCLUSIÓN: En la RL/R de la FVV, la técnica Extravesical ofrece ventajas técnicas y perioperatorias, por lo cual debe ser la técnica de elección para la mayoría de las FVV con indicación de abordaje abdominal. La técnica Transvesical se debe reservar para fístulas recurrentes,múltiples, inflamatorias, de dificil localización del orificio fistuloso, con excesiva proximidad de los meatos y con inminente necesidad de reimplante ureteral

OBJECTIVE: In the laparoscopic/robotic repair (L/R R) of Vesico-vaginal Fistulas (VVF) two types of transvesical and extravesical approaches are used.However, no direct comparisons exist between both surgical approaches Moreover, a lack of clinical guidelines is currently ongoing. Therefore, the selection of the type of approach is based on the preferences of the surgeon without considering the characteristics of each case.In order to provide recommendations for the selection of the appropriate technique for each patient, we designed a study that identifies and evaluates differences between the Transvesical and Extravesical approaches in the L/R R of the VVF. PATIENTS AND METHODS: A total of 9 patients withVVF were included. Four patients underwent transvesicaltechnique and the rest the Extravesical technique. Thevariables in each group were recorded. Surgical stepswere selected with technical differences to be analyzed(identification of the fistula, dissection of the vesico-vaginalplane, cystotomy, maneuvers of exposure and cystorrhaphy). RESULTS: Short operative times and catheterization times were recorded in the Extravesical approach. Intraoperative blood loss was minimal in both groups, the hospital stay was very similar and no peri and post-operativec omplications were reported. In all cases the fistula was resolved and there have been no recurrences in a mean follow-up of 35 months. Technically, Extravesical approach minimizes the size of the cystotomy, decreases suture time, does not require maneuvers for adequate exposure, and simplifies cystorrhaphy with respect to Transvesical technique, at the expense of requiring further dissection and having a slight difficulty in locating the fistula. Transvesical technique simplifies the locationof the fistula and allows better intravesical visualization. CONCLUSION: In the L/R R of the VVF, the Extravesicaltechnique offers technical and perioperative advantages,so it must be the technique of choice for most VVFwith indication of abdominal approach. Transvesicaltechnique should be reserved for recurrent, recurrent,inflammatory fistulas, with difficulties identifying the fistulous orifice, close to ureteric orifice and with imminent need for ureteral reimplantation

EGFR inhibition in glioma cells modulates Rho signaling to inhibit cell motility and invasion and cooperates with temozolomide to reduce cell growth.

Enforced EGFR activation upon gene amplification and/or mutation is a common hallmark of malignant glioma. Small molecule EGFR tyrosine kinase inhibitors, such as erlotinib (Tarceva), have shown some activity in a subset of glioma patients in recent trials, although the reported data on the cellular basis of glioma cell responsiveness to these compounds have been contradictory. Here we have used a panel of human glioma cell lines, including cells with amplified or mutant EGFR, to further characterize the cellular effects of EGFR inhibition with erlotinib. Dose-response and cellular growth assays indicate that erlotinib reduces cell proliferation in all tested cell lines without inducing cytotoxic effects. Flow cytometric analyses confirm that EGFR inhibition does not induce apoptosis in glioma cells, leading to cell cycle arrest in G(1). Interestingly, erlotinib also prevents spontaneous multicellular tumour spheroid growth in U87MG cells and cooperates with sub-optimal doses of temozolomide (TMZ) to reduce multicellular tumour spheroid growth. This cooperation appears to be schedule-dependent, since pre-treatment with erlotinib protects against TMZ-induced cytotoxicity whereas concomitant treatment results in a cooperative effect. Cell cycle arrest in erlotinib-treated cells is associated with an inhibition of ERK and Akt signaling, resulting in cyclin D1 downregulation, an increase in p27(kip1) levels and pRB hypophosphorylation. Interestingly, EGFR inhibition also perturbs Rho GTPase signaling and cellular morphology, leading to Rho/ROCK-dependent formation of actin stress fibres and the inhibition of glioma cell motility and invasion.

Gender dimorphism in high-fat-diet-induced insulin resistance in skeletal muscle of aged rats.

Muscle resistance to insulin plays a key role in the metabolic dysregulation associated to obesity. A pro-inflammatory and pro-oxidant status has been proposed to be the link between dietary obesity and insulin resistance. Given the gender differences previously found in mitochondrial function and oxidative stress, the aim of the present study was to investigate whether this gender dimorphism leads to differences in the development of high-fat-diet-induced insulin resistance in rat skeletal muscle. Male and female rats of 15 months of age were fed with a high-fat-diet (32% fat) for 14 weeks. Control male rats showed a more marked insulin resistance status compared to females, as indicated by the glucose tolerance curve profile and the serum insulin, resistin and adiponectin levels. High-fat-diet feeding induced an excess of body weight of 16.2% in males and 38.4% in females, an increase in both muscle mitochondrial hydrogen peroxide production and in oxidative damage, together with a decrease in the Mn-superoxide dismutase activity in both genders. However, high-fat-diet fed female rats showed a less marked insulin resistance profile than males, higher mitochondrial oxygen consumption and cytochrome c oxidase activity, and a better capacity to counteract the oxidative-stress-dependent insulin resistance through an overexpression of both muscle UCP3 and GLUT4 proteins. These results point to a gender dimorphism in the insulin resistance status and in the response of skeletal muscle to high-fat-diet feeding which could be related to a more detrimental effect of age in male rats.

Gender related differences in paraoxonase 1 response to high-fat diet-induced oxidative stress.

OBJECTIVE: To evaluate the influence of the pro-oxidant and proinflammatory state related to dietary obesity on serum paraoxonase 1 (PON1) activity in male and female rats. METHODS AND PROCEDURES: Adult Wistar rats of both genders were fed on a high-fat diet to induce weight gain or standard diet for 14 weeks. Body weight was assessed weekly and food intake fortnightly throughout the dietary treatment. Biometrical parameters and serum lipid profile, glucose, insulin, and adipokine levels were measured. To assess the effect of dietary obesity on oxidative stress, levels of liver and serum thiobarbituric acid reactive substances, liver protein carbonyl groups, liver antioxidant enzymes activities, and serum PON1 activities were measured. RESULTS: High-fat diet feeding induced a significant body weight gain in both male and female rats, as well as a reduction of liver antioxidant protection. High-fat diet increased serum lipid peroxides in male rats and reduced serum PON1 activities and serum apolipoprotein A-I (apoA-I) levels in females, although did not alter serum PON1 or apolipoprotein J (apoJ) levels. DISCUSSION: Our results reveal a gender dimorphism in the high-fat diet-induced reduction of serum PON1 activity, which is likely to be related to the greater obese and proinflammatory state achieved in female rats. We suggest that the enhanced oxidative stress caused by dietary increased body weight, on leading to high-density lipoprotein (HDL), apoA-I or PON1 oxidation could entail the destabilization of the PON1 association to HDL or a direct inactivation of PON1 enzymatic activity, thus accounting for the decreased serum PON1 activities observed in female rats.

Paraoxonase 1 response to a high-fat diet: gender differences in the factors involved.

Diets consumed in industrialized countries are rich in fat and increase the incidence of atherosclerosis, a process reported to be influenced by gender. Considering the anti-atherogenic role attributed to serum Paraoxonase 1 (PON1) activity, and given the pro-atherogenic effects described for saturated fatty acids (SFA), as opposed to the beneficial ones conferred to monounsaturated fatty acids (MUFA), the aim of this study was to investigate the response of male and female rat serum PON1 activity and its related factors to a high-fat (HF), hypercaloric diet (fat representing 55.2% of the energy) containing similar amounts of SFA and MUFA. The HF diet feeding did not alter total body weight, but increased adiposity. Nevertheless, and in spite of the increased adiposity, the HF diet did not entail a more pro-inflammatory serum adipokine or lipid profile or increased lipid peroxidation. Paraoxonase activity was reduced in both male and female HF fed rats, due to a reduction of PON1 mRNA levels in males and to a reduced stability and/or number of HDL particles responsible for PON1 transport in females. Both the maintenance of body weight and the MUFA content in the diet would be among the factors responsible for the attenuation of the negative effects usually related to excessive fat intake and for the reduction in PON activity, whose antioxidant activity would be less necessary in this situation.

Time-dependent modulation of rat serum paraoxonase 1 activity by fasting.

High-density lipoprotein-associated paraoxonase 1 (PON1) protects the endothelium from the pro-oxidant activity of oxidised low-density lipoprotein. Whereas fasting has been related to increased oxidative stress, intermittent fasting and caloric restriction are associated to increased resistance to oxidative injury. Taking into consideration that serum PON1 activity is modulated by a restriction of caloric intake and because there is no evidence regarding PON1 response to total food deprivation, we investigated whether PON1 activity is involved in the response aimed to counteract the greater oxidative stress associated to fasting and whether serum PON1 activity is altered by the length of food deprivation. Male Wistar rats were randomly divided into five groups: fed and 6-, 12-, 24- or 48-h fasted rats. Serum PON1 activity increases within the first hours of fasting, representing a prompt adaptation designed to attenuate blood lipid peroxidation that cannot be sustained when fasting is prolonged. This PON1 response to early fasting could be part of the mechanisms triggered by periodically repeated short periods of food deprivation - intermittent fasting - which result in increased resistance to stress by stimulating antioxidant defences.

The age-related paraoxonase 1 response is altered by long-term caloric restriction in male and female rats.

Caloric restriction (CR) has been shown to attenuate age-related oxidative damage and to improve major atherosclerotic risk factors. Paraoxonase 1 (PON1), an enzyme specifically associated with HDL containing apolipoproteins A-I and J, has been reported to prevent the proatherosclerotic effects of oxidized LDL. The aim of this study was to evaluate whether modulation of PON1 activity is part of the underlying CR mechanisms that attenuate the age-associated negative effects. Experimental groups were 1 year old rats of both genders subjected to 40% CR for 1 year and two ad libitum-fed groups, also including rats of both genders, euthanized at 6 months or 2 years. Aging impaired the serum lipid profile and increased lipid peroxidation, PON1 activities, and the content of both PON1 and apolipoprotein J in HDL, which suggests an HDL subfraction redistribution to protect LDL more effectively from oxidation. The CR-associated improved lipid profile and the decreased lipid peroxide levels would lead to the decreased arylesterase activity seen in old CR animals, suggesting that PON1 modulation is not an integral part of the main antioxidant mechanisms of CR but rather that CR would determine a more youthful and less oxidative situation in which the protection of LDL would be less necessary.

Effects of caloric restriction and gender on rat serum paraoxonase 1 activity.

Paraoxonase 1 (PON1) associates to specific high-density lipoproteins (HDLs)--those containing apolipoprotein A-I (apoA-I) and apolipoprotein J (apoJ)--and is largely responsible for their antiatherogenic properties. Caloric restriction (CR) has been shown to reduce major atherosclerotic risk factors. The aims of this work were to study PON1 activity response to CR (40% over 14 weeks) and to elucidate whether there are adaptive differences related to gender. Serum and liver paraoxonase and arylesterase activities, serum triglyceride, total and HDL cholesterol concentrations, serum PON1, apoA-I and apoJ contents and liver PON1 mRNA levels were measured. No effects of CR or gender were observed in triglyceride, total cholesterol concentration and PON1 mRNA levels. HDL cholesterol was higher in female rats than in male rats and increased with CR only in the latter animals. Serum PON1 activities tended to be higher in female rats and dropped with CR, with females showing the biggest decrease. Serum PON1 content was higher in female rats and decreased in both genders with CR, whereas apoA-I and apoJ contents, which were higher in female rats too, decreased only in the former animals, accounting for the high PON1 activity decrease observed in these animals. In conclusion, the short-term CR-associated reduction of serum PON1 activity and PON1, apoA-I and apoJ levels points toward a reduced stability of HDL-PON1 complexes and/or HDL particle levels responsible for PON1 transport and function in the blood. Moreover, the variations in PON1 activity and apolipoprotein levels show gender-related differences that are indicative of a different adaptive strategy of male and female rats when faced with a period of food restriction.

Hamartosis y asimetría corporal / Harmartosis and body asymetric

En el presente trabajo se ha ilustrado 5 enfermedades que tienen en común la hipertrofia asimétrica de miembros: Klippel-Treanunay-Weber, Proteus, Ollier, Maffucci y Neurofibromatosis. Estas cinco entidades son poco conocidas. Se requiere mostrar sus características clínico-radiológicas mejorando así el diagnóstico y tratamiento de las mismas. La etiología en todos los casos es desconocida. No se ha encontrado transmisión hereditaria, excepto en la Neurofibromatosis. No van asociadas a retardo mental. Las características clínicas son: en el sindrome Klippel-Trenaunay-Weber: Hemangiomas, hiertrofia ósea y/o de tejidos blandos, varicosidades. En el sindrome proteus: gigantismo de manos y/o pies, hipertrofia ósea y/o de tejidos blando. En la enfermedad de Ollier: Encontromas.En el sindrome Maffucci: Encondromas y hemangiomas. Y en la Neurofibromatosis, manchas café con leche, nerufibromas, hipertrofia ósea y/o de tejidos blandos, escoliosis, angulación de la tibia. El pronóstico depende de las complicaciones, pero generalmente es benigno; en la mayoría de los casos, compatible con la vida normal. Los exámenes radiológicos son muy importantes para el diagnóstico y tratamiento, observándose imágenes de ensanchamiento, alargamiento, angulación, acortamiento óseo y anomalias vasculares entre otras. El tratamiento depende del cuadro de cada paciente siendo el rol más importante el del cirujano ortopédico, despús de haberse llegado a un diagnóstico multidisciplinario