Changes in environmental exposures over decades may influence the genetic architecture of severe spermatogenic failure.

STUDY QUESTION: Do the genetic determinants of idiopathic severe spermatogenic failure (SPGF) differ between generations? SUMMARY ANSWER: Our data support that the genetic component of idiopathic SPGF is impacted by dynamic changes in environmental exposures over decades. WHAT IS KNOWN ALREADY: The idiopathic form of SPGF has a multifactorial etiology wherein an interaction between genetic, epigenetic, and environmental factors leads to the disease onset and progression. At the genetic level, genome-wide association studies (GWASs) allow the analysis of millions of genetic variants across the genome in a hypothesis-free manner, as a valuable tool for identifying susceptibility risk loci. However, little is known about the specific role of non-genetic factors and their influence on the genetic determinants in this type of conditions. STUDY DESIGN, SIZE, DURATION: Case-control genetic association analyses were performed including a total of 912 SPGF cases and 1360 unaffected controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: All participants had European ancestry (Iberian and German). SPGF cases were diagnosed during the last decade either with idiopathic non-obstructive azoospermia (n = 547) or with idiopathic non-obstructive oligozoospermia (n = 365). Case-control genetic association analyses were performed by logistic regression models considering the generation as a covariate and by in silico functional characterization of the susceptibility genomic regions. MAIN RESULTS AND THE ROLE OF CHANCE: This analysis revealed 13 novel genetic association signals with SPGF, with eight of them being independent. The observed associations were mostly explained by the interaction between each lead variant and the age-group. Additionally, we established links between these loci and diverse non-genetic factors, such as toxic or dietary habits, respiratory disorders, and autoimmune diseases, which might potentially influence the genetic architecture of idiopathic SPGF. LARGE SCALE DATA: GWAS data are available from the authors upon reasonable request. LIMITATIONS, REASONS FOR CAUTION: Additional independent studies involving large cohorts in ethnically diverse populations are warranted to confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS: Overall, this study proposes an innovative strategy to achieve a more precise understanding of conditions such as SPGF by considering the interactions between a variable exposome through different generations and genetic predisposition to complex diseases. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the "Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020)" (ref. PY20_00212, P20_00583), the Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation (ref. PID2020-120157RB-I00 funded by MCIN/ AEI/10.13039/501100011033), and the 'Proyectos I+D+i del Programa Operativo FEDER 2020' (ref. B-CTS-584-UGR20). ToxOmics-Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, is also partially supported by the Portuguese Foundation for Science and Technology (Projects: UIDB/00009/2020; UIDP/00009/2020). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Do candidates for penile implant prefer their doctors or another implanted patient as their information source? Results of a pilot study.

INTRODUCTION: Erectile dysfunction incidence is about 19-26 cases for every 1000 men/year, requiring about 20,000 penile implants/year. There is high demand for information on the part of patients, however, there is a lack of evidence about the sources of information prior to penile implant and the figure of the Expert Patient (EP) has never been described in this area. AIMS: To evaluate the sources of information used by candidates for penile implant as well as to describe the role of the EP as an information source. METHODS: Pilot study of candidates for penile prosthesis. Patients already implanted attending for exchange or reallocation surgery were excluded. Each patient had an interview with an EP, and commercial documentation was given. Each source of information was evaluated in a face-to-face interview. SPSS™ version 20.0 was used. MAIN OUTCOME MEASURES: The EP was evaluated by the International Index of Erectile Function, the Generalized Anxiety Disorder 7 questionnaire, and the Erectile Dysfunction Inventory of Treatment Satisfaction. Each source of information was evaluated by a non-validated 6-section questionnaire. RESULTS: Ten patients were included. Mean age was 60±10.3 years. Medical interview with the urologist resulted in a global value and truthfulness score of 9.2±.9 and 9.8±.4, respectively. Commercial information had a global score of 8.5±.9 and a truthfulness score of 8.6±.6, while the internet had 6.8±.8 points for global value and 7.2±1 for truthfulness. The global score of the EP was 8.7±1.2 points and their veracity scored 9.6±.5 points. CONCLUSIONS: The urologist remains the main source of information for patients with erectile dysfunction candidates for penile prosthesis implant. However, the EP is an alternative and could be a key pillar in presurgical counselling.

[Andrology and penile cancer. Recommendations during COVID-19 pandemia.] / Andrología y cáncer de pene. Recomendaciones durante la pandemia COVID-19.

PURPOSE: The COVID-19 pandemic which has affected Spain since the beginning of 2020 compels us to determine recomendations for the practice of Andrology in present times. MATERIALS AND METHODS: A web search is carried out in English and Spanish and a joint proposal is defined by experts in Andrology from different regions of Spain. RESULTS: Most diagnostic and therapeutic procedures in Andrology can be safey postponed during the COVID-19 pandemic. Online consultations and outpatient surgeries must be encouraged. Andrologic emergencies and penile cancer management should be considered high priority, and should be diagnosed and treated promptly even in the most severe phases of the pandemic.

INTRODUCCIÓN: La pandemia COVID-19 que ha afectado a España desde comienzos de 2020 obliga a definir unas recomendaciones para la práctica de la Andrología en la actualidad.MATERIAL Y MÉTODOS: Se realiza una búsqueda web en inglés y español y se define una propuesta conjunta por parte de expertos en Andrología de distintas regiones de España.RESULTADOS: La mayor parte de los procedimientos diagnósticos y terapéuticos en Andrología pueden ser demorados con seguridad durante la pandemia COVID-19. Se debe fomentar la consulta telemática y la cirugía ambulatoria. Las urgencias andrológicas y el manejo del cáncer de pene deben considerarse una prioridad alta, diagnosticándose y tratándose con brevedadi ncluso en las fases más severas de la pandemia.

[Current state regarding fertility cryopreservation in pre-pubertal boys]. / Estado actual de la criopreservación de la fertilidad en varones prepúberes.

Some treatments for any cancer therapy and hematological diseases may have gonadotoxic side effects that can result in infertility, and thus sperm cryopreservation is routinely offered to patients as the strategy to preserve their fertility. However, there are many cases where sperm banking cannot be applied, as is the case of pre-pubertal cancer patients and others unable to produce mature gametes at the moment of diagnosis. Regarding this, recent breakthroughs have gained public attention to the fertility preservation options that Regenerative Medicine can offer to these patients. In this review, we tried to compile and discuss the latest updates about all these strategies from a critical point of view.

Congenital bilateral absence of the vas deferens (CBAVD): do genetic disorders modify assisted reproductive technologies outcomes? / Ausencia congénita bilateral del conducto deferente: ¿Modifican las alteraciones genéticas los resultados de las tecnicas de reproducción asistida?

OBJECTIVES: To evaluate the impact of common Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene mutations, 5T polymorphism and presence of severe Cystic Fibrosis (CF) on fertility outcomes with Assisted Reproductive Techniques (ART) in patients presenting Congenital Bilateral Absence of Vas Deferens (CBAVD). METHODS: A comparative observational cohort study was performed from 2002 to 2018 with 51 patients with diagnosis of CBAVD. Presence of CFTR mutations and 5T, CF, pregnancy and newborn rates were analyzed. RESULTS: 80.4% percent had some mutation of CFTR gene being ΔF508 the most common (51%). The most frequently described genotype was the 7T/9T (31.4%) with the presence of 5T polymorphism in up to 25.5% of cases. Global newborn rates were 34% in the group using partner spermatozoa. When comparing 5T presence, we observed a decrease in newborn rates when carrying this mutation, without obtaining statistical significance (newborn rate: 5T/non-5T: 7.1/28%, p 0.45). No differences were found when comparing presence of severe CF, common CFTR gene mutations and ICSI-related parameters. CONCLUSION: The analysis of the presence of 5T polymporphism in CBAVD patients may add information when predicting the outcome of assisted reproductive techniques.

OBJETIVOS: Evaluar el impacto de las mutaciones del gen CFTR regulador de la conductancia transmembrana de la fibrosis quística, los polimorfismos 5T y la presencia de fibrosis quística (FQ) grave en los resultados de fertilidad de las técnicas de reproducción asistida en pacientes que presentan ausencia bilateral congénita de conductos deferentes.MÉTODOS: Estudio comparativo observacional de cohortes realizado desde 2002 hasta 2018 con 51 pacientes con el diagnóstico de ausencia bilateral congénita de conductos deferentes. Se analizaron la presencia de mutaciones del gen CFTR y 5T, fibrosis quística y tasas de embarazo y nacimientos. RESULTADOS: 80,4% tenían alguna mutación del CFTR siendo la ΔF508 la más frecuente (51%). El genotipo descrito con mayor frecuencia era 7T/9T (31,4%) con la presencia de polimorfismo 5T en hasta el 25,5% de los casos. Las tasas de nacimientos globales fueron del 34% en el grupo que utilizaba espermatozoides del marido. Cuando se compara la presencia de 5T, observamos una disminución en las tasas de nacimientos en los portadores de esta mutación, sin obtener significación estadística (Tasa de nacimientos 5T/no-5T: 7,1/28%, p=0,45). No se encontraron diferencias en la comparativa entre la presencia de FQ severa, mutaciones comunes del gen CFTR y los parámetros relacionados con la ICSI. CONCLUSIONES: El análisis de la presencia de polimorfismo 5T en los pacientes con ausencia bilateral congénita de conductos deferentes puede añadir información para la predicción de los resultados de las técnicas de reproducción asistida.

Local Treatment of Penile Prosthesis Infection as Alternative to Immediate Salvage Surgery.

INTRODUCTION: Penile prosthesis (PP) is the established treatment for patients with erectile dysfunction (ED) who do not respond to phosphodiesterase inhibitors and intracavernosal injections. In general, these devices have been largely successful but there are not free of serious complication such as PP infection (PPI). PPI requires immediate surgical removal or salvage rescue of the PP. AIM: In this report, we present two clinical cases with inflatable PP (IPP) treated locally with antibiotic and high pressure irrigation and then avoid the PP removal or salvage rescue. METHODS: We present two patients with PPI in our institution and literature review. MAIN OUTCOME MEASURES: Resolution of the two cases. RESULTS: Patient A (A) was 44 years old and patient B (B) 51 years old presented PPI after three weeks (A) and eight weeks (B). Both patients were diabetic. Physical exploration revealed an open scrotal incision at its margin with a clear discharge. The rest of the incision and scrotum were clean and dry. They had not scrotum pain/tenderness or systemic/septic symptoms. The bacterial culture of the incisional drainage revealed a Staphylococcus aureus (A) and Staphylococcus epidermidis (B). In both cases, we performed an excision of the tissue around the pump with a high pressure pulsed irrigation (Interpulse; Stryker Corp, Kalamazoo, MI, USA). For the irrigation we used three different solutions that included povidone-iodine, antibiotics (gentamicin plus vancomicin), and hydrogen peroxyde. Finally, we performed a multilayered surgical closure with the use of aspirate drainage over 24 hours and intravenous antibiotics. The patients had a total resolution of its symptoms after 20 months (A) and 36 months (B), and the IPP worked properly. CONCLUSION: This treatment could be an option for to perform specific patients with local IPP infection without systemic symptoms instead of surgical removal.

[Metastatic urinary bladder involvement in breast cancer]. / AFECTACIÓN VESICAL METASTÁSICA DEL CÁNCER DE MAMA.

OBJECTIVE: To contribute to the literature with three unusual cases of primary breast tumor with metastasis to the urinary bladder. METHODS: Presentation of the three clinical cases and bibliographic review. RESULTS: Three women, with an average age of 49.3 years, were diagnosed with invasive lobular breast carcinoma. Two of them suffered from hematuria after being diagnosed with breast cancer. The third patient was diagnosed incidentally after a routine CT scan. Upon diagnosis of the bladder metastases, they already had metastasis in other locations. The treatment of the three cases was palliative. The cause of death was due to additional pathologies. CONCLUSIONS: The presence of bladder metastases due to breast cancer is infrequent. The appearance of urinary tract symptoms in these patients requires a diagnostic study in order to rule out metastases.