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The large HDL particles generated by administration of cholesteryl ester transfer protein inhibitors (CETPi) remain poorly characterized, despite their potential importance in the routing of cholesterol to the liver for excretion, which is the last step of the reverse cholesterol transport. Thus, the effects of the CETPi dalcetrapib and anacetrapib on HDL particle composition were studied in rabbits and humans. The association of rabbit HDL to the LDL receptor (LDLr) in vitro was also evaluated. New Zealand White rabbits receiving atorvastatin were treated with dalcetrapib or anacetrapib. A subset of patients from the dal-PLAQUE-2 study treated with dalcetrapib or placebo were also studied. In rabbits, dalcetrapib and anacetrapib increased HDL-C by more than 58% (P < 0.01) and in turn raised large apo E-containing HDL by 66% (P < 0.001) and 59% (P < 0.01), respectively. Additionally, HDL from CETPi-treated rabbits competed with human LDL for binding to the LDLr on HepG2 cells more than control HDL (P < 0.01). In humans, dalcetrapib increased concentrations of large HDL particles (+69%, P < 0.001) and apo B-depleted plasma apo E (+24%, P < 0.001), leading to the formation of apo E-containing HDL (+47%, P < 0.001) devoid of apo A-I. Overall, in rabbits and humans, CETPi increased large apo E-containing HDL particle concentration, which can interact with hepatic LDLr. The catabolism of these particles may depend on an adequate level of LDLr to contribute to reverse cholesterol transport.
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Anticolesterolemiantes , Humanos , Conejos , Animales , Anticolesterolemiantes/farmacología , Anticolesterolemiantes/uso terapéutico , Colesterol/metabolismo , Apolipoproteínas E/metabolismo , Proteínas de Transferencia de Ésteres de Colesterol/metabolismo , HDL-ColesterolRESUMEN
Environmental mercury (Hg) contamination of the global tropics outpaces our understanding of its consequences for biodiversity. Knowledge gaps of pollution exposure could obscure conservation threats in the Neotropics: a region that supports over half of the world's species, but faces ongoing land-use change and Hg emission via artisanal and small-scale gold mining (ASGM). Due to their global distribution and sensitivity to pollution, birds provide a valuable opportunity as bioindicators to assess how accelerating Hg emissions impact an ecosystem's ability to support biodiversity, and ultimately, global health. We present the largest database on Neotropical bird Hg concentrations (n = 2316) and establish exposure baselines for 322 bird species spanning nine countries across Central America, South America, and the West Indies. Patterns of avian Hg exposure in the Neotropics broadly align with those in temperate regions: consistent bioaccumulation across functional groups and high spatiotemporal variation. Bird species occupying higher trophic positions and aquatic habitats exhibited elevated Hg concentrations that have been previously associated with reductions in reproductive success. Notably, bird Hg concentrations were over four times higher at sites impacted by ASGM activities and differed by season for certain trophic niches. We developed this synthesis via a collaborative research network, the Tropical Research for Avian Conservation and Ecotoxicology (TRACE) Initiative, which exemplifies inclusive, equitable, and international data-sharing. While our findings signal an urgent need to assess sampling biases, mechanisms, and consequences of Hg exposure to tropical avian communities, the TRACE Initiative provides a meaningful framework to achieve such goals. Ultimately, our collective efforts support and inform local, scientific, and government entities, including Parties of the United Nations Minamata Convention on Mercury, as we continue working together to understand how Hg pollution impacts biodiversity conservation, ecosystem function, and public health in the tropics.
RESúMEN: La contaminación ambiental por mercurio (Hg) en los trópicos supera nuestra comprensión de sus consecuencias para la biodiversidad. Los vacíos de conocimiento que existen sobre la exposición a la contaminación podrían ocultar las amenazas para la conservación en el Neotrópico: una región que alberga a más de la mitad de las especies del mundo, pero que enfrenta una continua intensificación de las emisiones de Hg y del cambio de uso del suelo por el avance de la minería de oro artesanal y de pequeña escala (MAPE). Debido a su distribución global y su sensibilidad a la contaminación, las aves brindan una oportunidad valiosa como bioindicadores para evaluar cómo las emisiones de Hg afectan la capacidad de un ecosistema para sustentar la biodiversidad y, en última instancia, la salud global. Presentamos la más grande base de datos sobre concentraciones de Hg en aves Neotropicales (n = 2,316) para establecer una línea base para los niveles de exposición a Hg en 322 especies de aves de nueve países de América Central, América del Sur, y el Caribe. Encontramos patrones de las concentraciones de Hg en aves de los trópicos que se asemejan a los de las regiones templadas: mostrando una bioacumulación consistente a través de grupos funcionales y una alta variación espaciotemporal. Las especies de aves que ocupan posiciones más altas en la cadena trófica y en hábitats acuáticos registraron concentraciones elevadas de Hg que podrían tener efectos negativos en su éxito reproductivo. Es importante resaltar que las concentraciones de Hg en las aves de los sitios afectados por la MAPE fueron cuatro veces más altas que las de los sitios control y además difirió por temporada para ciertos nichos tróficos. Desarrollamos esta síntesis a través de una red de investigación colaborativa, la Iniciativa de Investigación Tropical para la Conservación y Ecotoxicología Aviar (TRACE), que ejemplifica un intercambio de datos inclusivo, equitativo e internacional. Si bien nuestros hallazgos sugieren una necesidad urgente de evaluar los sesgos en el muestreo, los mecanismos, y las consecuencias de la exposición al Hg en las comunidades de aves tropicales, la Iniciativa TRACE proporciona un marco para abordar estos objetivos. Nuestro esfuerzo colectivo tiene como propósito respaldar y brindar información a las entidades locales, científicas, y gubernamentales, incluyendo las Partes de la Convención de Minamata de las Naciones Unidas sobre el Mercurio, mientras continuamos trabajando juntos para comprender cómo la contaminación por Hg en los trópicos puede afectar la salud pública, el funcionamiento de los ecosistemas, y la conservación de la biodiversidad. Total mercury (THg) concentrations (µg/g) and sample sizes of birds across Central America, South America, and the West Indies from 20072023. Point size and color are arranged in order of increasing THg concentration and hexagonal grid cells are colored in terms of increasing sample size.
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Mercurio , Animales , Mercurio/análisis , Monitoreo del Ambiente , Ecosistema , Contaminación Ambiental , Oro , AvesRESUMEN
INTRODUCTION: Support care aims to improve the experience of patients. m-health is one of the tools recently developed to promote patient empowerment. The objective of this study was to evaluate the appreciation of an m-health application to enhance prostatectomy path for patients suffering from prostate cancer. METHOD: A prospective monocentric study was conducted in the urology department of the University Hospital of Rennes from February to April 2023. MyCHU application was optimized by integrating information sheets in the postoperative period after prostatectomy on sphincter rehabilitation exercises, erectile dysfunction and urinary incontinence. The questionnaire used to evaluate the usability of "MyCHU" application was the System Usability Scale (SUS). Semi-structured interviews explored the patients' feelings about the content of the information sheets and the impact on their empowerment regarding sexual disorders. RESULTS: Twelve patients participated in this study and 7 agreed to complete an interview The average SUS score was 75.58, which indicate an high usability. Patients appreciated the fact that the application structured their healthcare pathway by centralizing information. The information sheets were clear and accurate. The impact on their empowerment was positive, with a gain in their ability to take ownership of the therapies. CONCLUSION: The role of digital technology in health care has been growing in recent years. Our study has shown the interest that mobile application can bring to the patient who undergoes prostatectomy. It increases his empowerment and favor the dialogue with his surgeon.
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Prostate cancer (PCa) is a public health issue. The diagnostic strategy for PCa is well codified and assessed by digital rectal examination, PSA testing and multiparametric MRI, which may or may not lead to prostate biopsies. The formal benefit of organized PCa screening, studied more than 10 years ago at an international scale and for all incomers, is not demonstrated. However, diagnostic and therapeutic modalities have evolved since the pivotal studies. The contribution of MRI and targeted biopsies, the widespread use of active surveillance for unsignificant PCa, the improvement of surgical techniques and radiotherapy have allowed a better selection of patients and strengthened the interest for an individualized approach, reducing the risk of overtreatment. Aiming to enhance coverage and access to screening for the population, the European Commission recently promoted the evaluation of an organized PCa screening strategy, including MRI. The lack of screening programs has become detrimental to the population and must shift towards an early detection policy adapted to the risk of each individual.
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Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/patología , Próstata/patología , Antígeno Prostático Específico , Biopsia , Imagen por Resonancia Magnética/métodos , Detección Precoz del CáncerRESUMEN
Adapted physical activity (APA) appears to be essential for supportive care in oncology. It helps to reduce different side effects inherent to treatment and disease (e.g., fatigue, sarcopenia, balance problems) and could have an impact on patients' survival. However, it is not systematically implemented in daily practice and still too few patients reach the recommendations of physical activity. New tools, such as digital and connected ones, are now developed to overcome barriers to the implementation and daily practice of physical activity (e.g., distance between home and hospital). The aim of this article was to provide an overview of different connected tools that offer exercise training and monitoring programmes in prostate cancer.
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Neoplasias de la Próstata , Humanos , Masculino , Ejercicio Físico , Fatiga , Retroalimentación , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/tratamiento farmacológicoRESUMEN
INTRODUCTION: Women currently bear the most responsibility in contraception, with a wide choice of methods, while only a few existing male contraceptives are available. However, it has been shown that men are willing to get involved in birth control and to control their own fertility. Our research was focused on female population and a survey was carried out to explore women's perceptions of male contraception. METHODS: An observational quantitative cross-sectional study using a self-administered-questionnaire was carried out between November 2019 and February 2020. All women aged from 16-years-old to menopause completing the questionnaire were included. Descriptive statistical analyses were conducted, qualitative variables were expressed as counts and frequency. RESULTS: In total, 379 interpretable completed questionnaires were included. Among the women, 69.7% were in favour of letting men deal with contraception, without referring to a specific method. After having been made aware of the medical information concerning existing male contraceptives and those in development, the proportion of women in favour dropped to 46.7%. The most acceptable method for a majority of women was the male pill, which is still being developed. The majority (78.4%) of the women in our survey felt insufficiently informed about male contraception. DISCUSSION: In our study, women seemed to want to share contraceptive responsibility with men, but the lack of information and of acceptable contraception methods available remained an obstacle. Although larger-scale studies are needed to confirm these results, the development of a wider range of male contraception methods seems to be what both men and women have long been expecting.
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Anticoncepción , Adolescente , Anticoncepción/métodos , Estudios Transversales , Femenino , Humanos , Masculino , Encuestas y CuestionariosRESUMEN
PURPOSE: Periprostatic fat has a metabolic activity on the prostate via cytokines that act paracrine on several signaling pathways including tumorigenesis. We investigated whether there was an association between preprostatic fat abundance and prostate cancer (PCa) aggressiveness. MATERIALS AND METHODS: We performed a retrospective study including patients who underwent radical prostatectomy in our center from the prospective RESCAP database. Preoperative MRIs were re-read and different measurements of preprostatic fat (PPF) were performed. The maximum thickness (PPFmax) and the minimum thickness (PPFmin) were measured on a median T2 sagittal section. The total volume of preprostatic fat (PPFV) and volume normalized by prostate volume (NPPFV) were calculated semi-automatically by segmentation on continuous axial sections of 3mm. The association of these parameters with the aggressiveness criteria of PCa (ISUP 3-5 on biopsies and on operative specimen, intermediate or high-risk disease according to D'AMICO, PSA>10, upgrading risk at radical prostatectomy) was measured as well as the association between normal, overweight, and obese BMI classes and the aggressiveness criteria used. RESULTS: One hundred and twenty-one men were included in this study. In both the univariate analysis and the multivariate analysis, none of the preprostatic fat measurements (PPFmax, PPFmin, PPFV and NPPFV) were associated with PCa aggressiveness criteria. There was also no association between BMI class and tumor aggressiveness. CONCLUSION: In this study, there is no association between the abundance of preprostatic fat and PCa aggressiveness according to the periprostatic fat measurements achieved. LEVEL OF EVIDENCE: III.
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Próstata , Neoplasias de la Próstata , Humanos , Masculino , Clasificación del Tumor , Estudios Prospectivos , Próstata/diagnóstico por imagen , Próstata/patología , Prostatectomía , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Estudios RetrospectivosRESUMEN
The objective of this article was to discuss the statistics of surgical complications in urology and the methods of collection and classification. In the absence of a comprehensive national registry of complications, we used statistics from insurance companies as indicators. They are limited by the exclusion of complications that did not result in a claim. Overall, urology is less exposed to claims than other surgical specialties. It comes far behind orthopedic surgery, gynecology-obstetrics and visceral surgery. The new techniques in urological surgery and in particular the rise of robotic surgery do not seem to have modified the number of claims handled by medical insurance companies. It is unfortunate that complications in urological surgery are not collected, reported, and discussed in order to develop prevention, treatment, and strategies for educational purposes. The lack of an established definition and classification of surgical complications, as well as methodological differences in the collection of related information, has hampered the evaluation of their public health and health economics impact. Awareness of this problem is growing among learned societies and practitioners. Complication reporting should be organized on a national basis and should respect the following points: - definition of the collection process according to a validated system. For urology, the Martin table revised by the EAU working group would be adapted; - classification of complications according to a validated system such as Clavien-Dindo or CCI.
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Procedimientos Quirúrgicos Robotizados , Urología , Humanos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Procedimientos Quirúrgicos Robotizados/efectos adversosRESUMEN
INTRODUCTION: Surgical techniques of radical and partial nephrectomy have changed over the last 20years. Indications for partial nephrectomy have widened and mini-invasive surgery (laparoscopy and robotic assistance) has become widely used. However, both still have a significant morbidity. The objective of this article is to review complications of renal surgery and their predictive factors and to offer algorithms of management. METHODS: Recent literature regarding complications of radical and partial nephrectomy was queried using Pubmed engine search. The most relevant articles were analyzed and served as a basis for this work. RESULTS: The literature on complications of radical and partial nephrectomy has a low level of evidence. There are only retrospective series. The most frequent complications of radical nephrectomy occur during surgery in 5-10% of the cases: wound of the pedicle or of an adjacent organ. The management can often be conservative. Laparoscopy has a similar morbidity compare to the open approach but has greatly increased postoperative outcomes and comfort. Partial nephrectomy has a 20% complication rate. Many factors have an impact on the risk of complications (tumor size, inflammation of perirenal fat, access, surgeon experience, centre volume, comorbidities and age of the patient) and must be taken into consideration before advising partial nephrectomy. The two most feared complications of partial nephrectomy are bleeding (per- or postoperative, 10% of the cases) and urinary fistula (<5% of the cases). Robotic assistance is associated with a lower morbidity in many publications. CONCLUSION: Complications after partial and radical nephrectomy are quite frequent but have decreased with the improvement of surgical techniques. French urologists should maintain their interest in novel technologies and simplification of perioperative pathway to further improve patients' outcomes.
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Laparoscopía , Fístula Urinaria , Humanos , Riñón , Laparoscopía/efectos adversos , Nefrectomía/efectos adversos , Estudios RetrospectivosRESUMEN
The objective of this article was to summarize the means and tools of prevention and safety of care to reduce non-random surgical complications in urology, related to the care environment and the patient. The prevention of complications is an essential strategy to be applied in a standardized way in urological surgery, as in the world of aeronautics, from which we can draw valuable lessons. This prevention is multifactorial and concerns interventions, systems and human factors. The essential points listed below must be traceable: the quality of the assessment of the patient and his co-morbidities. This is a multidisciplinary task; the relevance of the surgical indication, which must take into account the state of the art at the time it is given; the expertise of the urologist and his continuing education; the relevance of the surgical indication, which must take into account the state of the art at the time it is given; the quality of the information provided to the patient and his family, and to the medical and paramedical team involved in the patient's care; the quality of the professional environment and equipment; compliance with recommended safety rules (e.g. checklist, identity check). All these points are not isolated but interdependent. They must be recorded in the patient's file, the quality and completeness of which is essential to the patient's follow-up, to the prevention and management of complications and to the understanding, if necessary, of the truth of the medical facts.
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Lista de Verificación , Urología , HumanosRESUMEN
CONTEXT-OBJECTIVE: The management of bladder tumors is based on two major interventions, the risks of complications of which can be significant. The objective of this work is to provide an update on the complications related to bladder surgery, to detail the preventive measures and management strategies in practice. METHODS: Bibliographic search using Medline bibliographic database (Pubmed) using the following keywords: transurethral resection of the bladder, cystectomy, neobladder, Bricker, complications, anastomotic strictures. RESULTS: Trans-urethral resection of the bladder (TURB) essentially exposes to the risk of hemorrhage (2 to 4%) and bladder perforation (1 to 3%). Total cystectomy is associated with significant morbidity and mortality, despite recent technical advances. The most frequent early complications are ileus (23 to 30%) and infectious complications (29 to 38%). Late complications included by functional complications (urinary and sexual), anastomotic strictures (7 to 12%), metabolic complications of continent derivation (25 to 46%) and stomial complications in case of non-continent derivation. The management of complications is well codified. It is however essential to anticipate and put in place preventive measures, especially for infectious and thromboembolic complications, including an exhaustive pre-operative assessment, prehabilitation of the patient and enhanced recovery after surgery. CONCLUSION: Preventing, analyzing and understanding complications in bladder surgery is essential to reduce mortality and morbidity.
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Complicaciones Posoperatorias , Vejiga Urinaria , Humanos , Constricción Patológica , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Procedimientos Quirúrgicos Urológicos/efectos adversos , Cistectomía/efectos adversosRESUMEN
Prostate surgery mainly addresses the treatment of the two most common pathologies of the prostate: benign prostatic hypertrophy (BPH), symptomatic or complicated, and prostate cancer (PCa). The objective of this manuscript was to present after review of the literature the main intraoperative and postoperative surgical complications associated with radical prostatectomy and surgery of the BPH whatever the surgical approach. The incidence and type of these complications may vary depending on the patient's comorbidities and the type of surgery. Regarding radical prostatectomy, the main complications are hemorrhagic, digestive and urinary. During or after surgery of BPH, hemorrhagic and urinary complications dominate. The management of these complications relies on general principles based on a low level of evidence, but usually associate a structured diagnostic pathway and an appropriate treatment decision.
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Hiperplasia Prostática , Neoplasias de la Próstata , Masculino , Humanos , Hiperplasia Prostática/cirugía , Hiperplasia Prostática/diagnóstico , Próstata/patología , Prostatectomía/efectos adversos , Neoplasias de la Próstata/patología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugíaRESUMEN
If surgical treatment of urinary stones is indicated, the urologist has now different modalities depending on each situation. This includes extracorporeal lithotripsy, ureteroscopy (rigid and flexible), and percutaneous nephrolithotomy. Ureteroscopy is also performed for diagnostic purposes, and for the treatment of upper urinary tract tumors. Indications, as well as the steps of each of these techniques will not be discussed in this review. Only intra- and postoperative complications of ureteroscopy and percutaneous nephrolithotomy will be reviewed, including diagnostic, management, and preventive measures.
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Litotricia , Nefrolitotomía Percutánea , Cálculos Urinarios , Urolitiasis , Humanos , Ureteroscopía/efectos adversos , Ureteroscopía/métodos , Nefrolitotomía Percutánea/efectos adversos , Litotricia/métodos , Urolitiasis/terapia , Cálculos Urinarios/cirugíaRESUMEN
Pelvic and perineal surgeries and in particular those for stress urinary incontinence and prolapse are functional surgeries, which require careful selection of patients and assessment of discomfort to expect satisfactory surgical results and reduce failure rates and of complications. Before offering pelvic and perineal surgery, the risk of potential complications should be carefully assessed and discussed with patients. Recent attention to the potential complications prosthetic mesh has raised awareness in the urological community to report complications. This chapter will focus on the complications of surgeries used for stress urinary incontinence (synthetic retropubic or transobturator suburethral slings, colposuspension, pubovaginal slings, artificial urinary sphincter, adjustable periurethral balloons and periurethral injections of bulking agents) and sacrocolpopexies. The epidemiology of complications, the minimum assessment to be carried out, treatment and prevention will be discussed.
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Cabestrillo Suburetral , Incontinencia Urinaria de Esfuerzo , Urología , Humanos , Incontinencia Urinaria de Esfuerzo/cirugía , Procedimientos Quirúrgicos Urológicos/efectos adversos , Procedimientos Quirúrgicos Urológicos/métodos , PelvisRESUMEN
AIM: Define and present the complications of surgery of the external genitalia (EG), as well as their management. METHOD: Bibliographic search using the Medline (NLM Pubmed tool) and Embase bibliographic databases using the following keywords: scrotal surgery, orchidopexy, hydrocele, varicocele, testicular biopsy, vasectomy, cryptorchidism, orchiectomy, testicular implant, subcapsular orchiectomy, spermatic cord cyst, posthectomy, penis curvature surgery, penile implant, urethral strictures. RESULTS: EG surgery is common in urology, it includes scrotal surgeries and penile surgeries, which are performed openly. They expose to complications such as bleeding, infection, scar disunity requiring early reassessment especially in case of ambulatory procedure. Rare complications must be known, some of which must lead to expert management. CONCLUSION: Complications of surgical treatment of EG should be identified and managed. This report should allow a better understanding and management of these complications.
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Criptorquidismo , Prótesis de Pene , Urología , Masculino , Adulto , Humanos , Pene/cirugíaRESUMEN
OBJECTIVE: Delayed graft function (DGF) is a common complication after transplantation of deceased donor kidneys. The aim of this study was to investigate the feasibility of using computed tomography texture analysis (CT-TA) of the donor kidney to predict delayed graft function (DGF) following kidney transplantation from cadaveric donors. MATERIALS AND METHODS: We made a retrospective review of all consecutive DBD and DCD kidney donors admitted to our institution and their corresponding KTRs between December 2014 and January 2019. We extracted 15 image features from unenhanced CT and contrast-enhanced CT corresponding to first order and second order Haralick textural features. Predictors of DGF were evaluated by univariable and multivariable analysis. Receiver operating characteristic (ROC) analysis was performed and the area under the ROC curve (AUC) to predict DGF was calculated for the predictors. RESULTS: A total of 115 patients were included in the study. DGF occurred in 15 patients (13%). Recipient body mass index (BMI) (P=0.003) and Skewness (P=0.05) represented independent predictors in the multivariate model. The combination of both clinical and textural features in a bivariate model reached a ROC-AUC of 0.79 (95% CI: 0.64-0.94) in predicting the probability of DGF. CONCLUSION: Results from this preliminary study suggest that CT texture analysis might be a promising quantitative imaging tool to help physician predict DFG after kidney transplantation from cadaveric donors. LEVEL OF EVIDENCE: 4/5.
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Trasplante de Riñón , Cadáver , Funcionamiento Retardado del Injerto/diagnóstico por imagen , Funcionamiento Retardado del Injerto/etiología , Supervivencia de Injerto , Humanos , Riñón , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Donantes de Tejidos , Tomografía Computarizada por Rayos XRESUMEN
The first part of this article deals with accreditation of the quality of the professional practice of urologists and medical teams working in public or private health care institutions. This is a voluntary national risk management process based on the reporting and analysis of medical risk events and the development and implementation of recommendations. The fundamental objective of the system is to reduce the frequency and severity of adverse events associated with care for the patient. The second part aims to describe the mechanisms and management of surgical complications. The perception of complications by the urologist is discussed, as it may be distorted by cognitive biases leading to inappropriate actions. Two important points were also emphasized: communication with the patient following an injury, therapeutic hazard or complication following an error, and proper maintenance of the medical record. A joint effort to cultivate a culture of safety and quality in urological surgical practice should be encouraged. Collective actions by urologists in the future should help to maintain a proactive attitude: - generalization of quality accreditation of urologic physicians' professional practice; - national registry: which has demonstrated its advantages in the world of aeronautics; - creation of a specific module "Management of complications in urology" in teaching (ECU) and continuing education (SUC, website); - creation of an AFU "Complications" Committee; - management of social networks.
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Urólogos , Urología , Humanos , Urología/educación , Procedimientos Quirúrgicos Urológicos/efectos adversos , Gestión de Riesgos , PredicciónRESUMEN
INTRODUCTION: Current therapeutic developments in prostate cancer (PCa) tend to increasingly personalize the treatment strategy, in particular as a function of tumor genomics. Recently, poly ADP-ribose polymerase (PARPi) inhibitors have shown their efficacy at the stage of castration resistance, in case of alteration of DNA repair genes in tumor tissue. MATERIAL AND METHODS: A narrative review was carried out on recent data in the literature since 2000. A consensus among the members of the Committee was obtained in order to synthesize the current data, with a particular focus on the practical considerations regarding indications and developments of molecular testing circuits concerning DNA repair genes, for theranostics purpose. RESULTS: The establishment of an efficient molecular testing network is based on the multidisciplinary organization of the various actors and the coordination of all material resources. Its goal is the routine search for somatic mutations (in tumor tissue) of BRCA1/2 genes in patients who may benefit from PARPi. The current indications are for BRCA1 or 2 mutated castration-resistant metastatic PCa after next-generation hormone therapy failure. The demand for molecular testing must be decided in the tumor board, giving priority to archived tissue less than 10 years old. In case of unsuccess, biopsies of the primary or metastases, or even analysis of circulating tumor DNA, may be necessary. Any demand for a genetic test on tumor tissue must be accompanied by detailed information for the patient on the possible familial consequences, in case of associated germline mutation. CONCLUSION: This article aims to guide the practical implementation of molecular testing circuits for DNA repair genes alterations, in order to guide the therapeutic management of patients with advanced PCa.
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Neoplasias de la Próstata Resistentes a la Castración , Urología , Niño , Reparación del ADN/genética , Pruebas Genéticas , Genómica , Humanos , Masculino , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genéticaRESUMEN
INTRODUCTION: The risk of recurrence is increased in localized high-risk prostate cancer (PCa). The implementation of an appropriate diagnostic and therapeutic strategy is essential. The objective of this update by the Prostate Committee of the French Association of Urology was to report the most recent data in the management of localized high-risk PCa. MATERIAL AND METHODS: This update is based on the data available in the literature on localized high-risk PCa. A PubMed search and narrative review of the recent data were performed in March 2022. RESULTS: Compared with conventional imaging, PET-PSMA is more effective for the diagnosis of lymph nodes and distant metastases. Two recent randomized clinical trials have failed to prove the oncologic benefit of extended pelvic lymph node dissection during radical prostatectomy (RP). Postoperatively, early salvage radiotherapy is the standard of care, with adjuvant radiotherapy becoming an option in case of unfavorable pathological criteria (ISUP 4-5, pT3±positive margins) in young patients. Although promising, perioperative systemic therapies (chemotherapy, second-generation hormonotherapy) cannot be recommended at this time when the patient is treated by RP. Regarding radiotherapy, prophylactic lymph node irradiation during prostatic irradiation was associated with improved biochemical and metastasis-free survival in a recent randomized trial but it is still controversial. Since the publication of the results of the STAMPEDE trial, the addition of abiraterone acetate to radiation-hormone therapy should be considered the new standard of care for patients with localized (very) high-risk PCa, according to the inclusion criteria of the study. CONCLUSION: The most recent data of the literature regarding the management of high-risk localized PCa redefine the diagnostic performance of molecular imaging, the timing of postoperative radiotherapy, the oncologic benefit of pelvic lymph node treatment, and the intensification of systemic therapies.
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Neoplasias de la Próstata , Urología , Humanos , Escisión del Ganglio Linfático , Masculino , Próstata , Antígeno Prostático Específico , ProstatectomíaRESUMEN
OBJECTIVE: The objective of the French Urology Association Cancer Committee is to propose an update of the recommendations for the diagnosis and management of prostate cancer (PC). METHODS: A systematic review of the literature from 2020 to 2022 was conducted by the CCAFU on the diagnosis and therapeutic management of localised PC, while evaluating the references and their levels of evidence. RESULTS: The recommendations specify the genetics, epidemiology and means of diagnosing prostate cancer, as well as the notions of screening and early detection. MRI, the gold standard imaging examination for localised cancer, is recommended before prostate biopsies are performed. The transperineal approach reduces the risks of infection. The therapeutic methods are described and recommended according to the clinical context. Active surveillance is the gold standard of treatment for tumours with a low risk for progression. Early salvage radiotherapy is recommended in case of biochemical recurrence after radical prostatectomy. Imaging, particularly molecular imaging, helps to guide the decision-making in the event of biochemical recurrence after local treatment, but should not delay early salvage radiotherapy in the event of biological recurrence after radical prostatectomy. CONCLUSION: This update of the French recommendations should help to improve the management of patients with PC.