Type-1 cannabinoid receptors and their ever-expanding roles in brain energy processes.

The brain requires large quantities of energy to sustain its functions. At the same time, the brain is isolated from the rest of the body, forcing this organ to develop strategies to control and fulfill its own energy needs. Likely based on these constraints, several brain-specific mechanisms emerged during evolution. For example, metabolically specialized cells are present in the brain, where intercellular metabolic cycles are organized to separate workload and optimize the use of energy. To orchestrate these strategies across time and space, several signaling pathways control the metabolism of brain cells. One of such controlling systems is the endocannabinoid system, whose main signaling hub in the brain is the type-1 cannabinoid (CB1 ) receptor. CB1 receptors govern a plethora of different processes in the brain, including cognitive function, emotional responses, or feeding behaviors. Classically, the mechanisms of action of CB1 receptors on brain function had been explained by its direct targeting of neuronal synaptic function. However, new discoveries have challenged this view. In this review, we will present and discuss recent data about how a small fraction of CB1 receptors associated to mitochondrial membranes (mtCB1 ), are able to exert a powerful control on brain functions and behavior. mtCB1 receptors impair mitochondrial functions both in neurons and astrocytes. In the latter cells, this effect is linked to an impairment of astrocyte glycolytic function, resulting in specific behavioral outputs. Finally, we will discuss the potential implications of (mt)CB1 expression on oligodendrocytes and microglia metabolic functions, with the aim to encourage interdisciplinary approaches to better understand the role of (mt)CB1 receptors in brain function and behavior.

An enquiry to the role of CB1 receptors in neurodegeneration.

Neurodegenerative disorders are debilitating conditions that impair patient quality of life and that represent heavy social-economic burdens to society. Whereas the root of some of these brain illnesses lies in autosomal inheritance, the origin of most of these neuropathologies is scantly understood. Similarly, the cellular and molecular substrates explaining the progressive loss of brain functions remains to be fully described too. Indeed, the study of brain neurodegeneration has resulted in a complex picture, composed of a myriad of altered processes that include broken brain bioenergetics, widespread neuroinflammation and aberrant activity of signaling pathways. In this context, several lines of research have shown that the endocannabinoid system (ECS) and its main signaling hub, the type-1 cannabinoid (CB1) receptor are altered in diverse neurodegenerative disorders. However, some of these data are conflictive or poorly described. In this review, we summarize the findings about the alterations in ECS and CB1 receptors signaling in three representative brain illnesses, the Alzheimer's, Parkinson's and Huntington's diseases, and we discuss the relevance of these studies in understanding neurodegeneration development and progression, with a special focus on astrocyte function. Noteworthy, the analysis of ECS defects in neurodegeneration warrant much more studies, as our conceptual understanding of ECS function has evolved quickly in the last years, which now include glia cells and the subcellular-specific CB1 receptors signaling as critical players of brain functions.

Unconsummated marriage: a systematic review of etiological factors and clinical management.

BACKGROUND: Unconsummated marriage (UCM) is the inability of the heterosexual married couple to have penovaginal sexual intercourse. AIM: The study sought to systematically review current evidence regarding the etiological factors and clinical management of UCM. METHODS: A comprehensive bibliographic search on the MEDLINE, Scopus, Web of Science, and Cochrane Library databases was performed in June 2023. Studies were selected if they described married couples who never had sexual intercourse in case report or case series evaluating the related causes and/or management and reporting data with qualitative, quantitative, or mixed methods. The review was reported according to PRISMA (Preferred Reporting Items for Systematic Review and Meta-analyses) statement and registered in PROSPERO with ID CRD42023433040. RESULTS: A total of 27 studies including 1638 males and 1587 females were selected. Eight (29.6%) articles were case reports involving a single couple and 19 (70.4%) studies were case series. Mean Murad score was 4.1 (range, 1-8) showing low-intermediate overall study quality. All articles had a level of evidence of 4. Most of studies were conducted in Egypt (n = 5 [18.4%]), Israel (n = 4 [14.9%]), and the United States (n = 4 [14.9%]). The mean age of males and females varied between 24.2 and 37.6 years and from 21 to 27.4 years, respectively. The reasons for the medical visit that led to the diagnosis of UCM were inability to consummate in 23 (85.2%) studies, inability to conceive in 1 (3.7%) article, and mixed in 3 (11.1%) articles. The mean duration of UCM varied from 7 days to 3.5 years. Eight studies involving both men and women showed that vaginismus (8.4%-81%) and erectile dysfunction (10.5%-61%) were the most common causes of UCM. Three articles reported that 16.6% to 26% of all UCM cases were due to both male and female factors. Sildenafil, tadalafil, intracavernosal injection, penile plication, female genital reconstructive surgery, vaginal dilators, lubricants, psychosexual therapy, and sex education were the various treatment modalities in 27 studies to achieve consummation rate of 66.6% to 100%. STRENGTHS & LIMITATIONS: A strength is that this is the first systematic review covering the entire spectrum of UCM. Limitations comprised the low quality of most of the included articles and the large percentage of UCM cases probably not published. CONCLUSION: Erectile dysfunction and vaginismus are the most reported causes of UCM; however, a strong psychological component certainly underlies a significant number of cases. A multidisciplinary approach based on strategic integration of sex education, medical therapy, psychosexual support, and surgical treatment would seem the most suitable option to manage couples with UCM.

Bidirectional astrocytic GLUT1 activation by elevated extracellular K.

The acute rise in interstitial K+ that accompanies neural activity couples the energy demand of neurons to the metabolism of astrocytes. The effects of elevated K+ on astrocytes include activation of aerobic glycolysis, inhibition of mitochondrial respiration and the release of lactate. Using a genetically encoded FRET glucose sensor and a novel protocol based on 3-O-methylglucose trans-acceleration and numerical simulation of glucose dynamics, we report that extracellular K+ is also a potent and reversible modulator of the astrocytic glucose transporter GLUT1. In cultured mouse astrocytes, the stimulatory effect developed within seconds, engaged both the influx and efflux modes of the transporter, and was detected even at 1 mM incremental K+ . The modulation of GLUT1 explains how astrocytes are able to maintain their glucose pool in the face of strong glycolysis stimulation. We propose that the stimulation of GLUT1 by K+ supports the production of lactate by astrocytes and the timely delivery of glucose to active neurons.

Aerobic Glycolysis in the Brain: Warburg and Crabtree Contra Pasteur.

Information processing is onerous. Curiously, active brain tissue does not fully oxidize glucose and instead generates a local surplus of lactate, a phenomenon termed aerobic glycolysis. Why engage in inefficient ATP production by glycolysis when energy demand is highest and oxygen is plentiful? Aerobic glycolysis is associated to classic biochemical effects known by the names of Pasteur, Warburg and Crabtree. Here we discuss these three interdependent phenomena in brain cells, in light of high-resolution data of neuronal and astrocytic metabolism in culture, tissue slices and in vivo, acquired with genetically-encoded fluorescent sensors. These sensors are synthetic proteins that can be targeted to specific cell types and subcellular compartments, which change their fluorescence in response to variations in metabolite concentration. A major site of acute aerobic glycolysis is the astrocyte. In this cell, a Crabtree effect triggered by K+ coincides with a Warburg effect mediated by NO, superimposed on a slower longer-lasting Warburg effect caused by glutamate and possibly by NH4+. The compounded outcome is that more fuel (lactate) and more oxygen are made available to neurons, on demand. Meanwhile neurons consume both glucose and lactate, maintaining a strict balance between glycolysis and respiration, commanded by the Na+ pump. We conclude that activity-dependent Warburg and Crabtree effects in brain tissue, and the resulting aerobic glycolysis, do not reflect inefficient energy generation but the marshalling of astrocytes for the purpose of neuronal ATP generation. It remains to be seen whether neurons contribute to aerobic glycolysis under physiological conditions.

Neuronal control of astrocytic respiration through a variant of the Crabtree effect.

Aerobic glycolysis is a phenomenon that in the long term contributes to synaptic formation and growth, is reduced by normal aging, and correlates with amyloid beta deposition. Aerobic glycolysis starts within seconds of neural activity and it is not obvious why energetic efficiency should be compromised precisely when energy demand is highest. Using genetically encoded FRET nanosensors and real-time oxygen measurements in culture and in hippocampal slices, we show here that astrocytes respond to physiological extracellular K+ with an acute rise in cytosolic ATP and a parallel inhibition of oxygen consumption, explained by glycolytic stimulation via the Na+-bicarbonate cotransporter NBCe1. This control of mitochondrial respiration via glycolysis modulation is reminiscent of a phenomenon previously described in proliferating cells, known as the Crabtree effect. Fast brain aerobic glycolysis may be interpreted as a strategy whereby neurons manipulate neighboring astrocytes to obtain oxygen, thus maximizing information processing.

Cadaveric Penile Prosthesis Workshop training improves surgical confidence levels of urologists: South Asian Society for Sexual Medicine course survey.

OBJECTIVES: To analyze the impact of South Asia's first cadaveric hands-on workshop on urologists' training in inflatable penile prosthesis surgery. METHODS: A total of 72 urologists/andrologists participated in the 2019 South Asian Society for Sexual Medicine Pre-congress Penile Prosthesis hands-on workshop. The workshop included 4 h of lectures and 2 h of hands-on cadaveric laboratory experience using three-piece inflatable penile prosthesis. The Shapiro-Wilk test was used on self-rated procedural confidence levels, which proved the normality. A non-parametric McNemar test was used to examine the change in the number of correct answers. RESULTS: Of those who attended the cadaver laboratory, just 45 who answered the survey both before and after the workshop were included for analysis. Significant objective improvements were noted in procedural knowledge test scores (44.30 ± 0.027 vs 72.44 ± 0.024, P < 0.05) and median surgical confidence levels (4 vs 3 and 2, P < 0.001) of the urologists after the completion of the workshop. CONCLUSIONS: Cadaveric hands-on workshop training improves urologists' procedural knowledge and surgical confidence levels in carrying out three-piece inflatable penile prosthesis surgery. The feasibility of such workshops should be considered in increasing the surgical expertise of general urologists in prosthetic urology.

Penile traction therapy with the new device 'Penimaster PRO' is effective and safe in the stable phase of Peyronie's disease: a controlled multicentre study.

OBJECTIVES: To evaluate the efficacy and safety of a new penile traction device (PTD), 'Penimaster PRO', in a group of patients with stable Peyronie's disease (PD) compared with a non-intervention group in a multicentre study. MATERIAL AND METHODS: A total of 93 patients with chronic stable PD (without erectile dysfunction, with no significant pain, and with a unidirectional curvature of at least 45° being stable for > 3 months) were recruited and followed for a 12-week period. Of these patients, 47 were randomly assigned to the Penimaster PRO group (PG) and 46 to the non-intervention group (NIG). Patients were asked to apply the PTD 3-8 h a day for 12 consecutive weeks, with specific instructions regarding the progressive increase of traction force applied to the penis over time. The primary outcome of the study was the change in the degree of curvature measured in the fully erect state after intracavernosal injection of alprostadil at baseline, 1, 2 and 3 months. Other variables, such as the type of curvature, stretched penile length (SPL), Peyronie's Disease Questionnaire (PDQ) scores, erectile function domain of the International Index of Erectile function (IIEF-EF) score and adverse events (AEs) were also assessed in each visit. RESULTS: Forty-one patients in the PG and 39 in the NIG completed the study. There was an overall reduction in curvature of 31.2° (P < 0.001) at 12 weeks compared to baseline in the PG, representing a 41.1% improvement from baseline, which significantly correlated with the number of daily hours the device was applied in a dose-dependent manner. Those patients using the device < 4 h/day experienced a reduction of 15°-25° (mean 19.7°, 28.8% improvement; P < 0.05), while patients using the device > 6 h/day experienced greater curvature reduction, ranging from 20° to 50° (mean of 38.4°, 51.4% improvement; P < 0.001). In contrast, no significant changes in curvature were observed in the NIG. Furthermore, SPL increased significantly in the PG compared to baseline and compared with the NIG, ranging from 0.5 to 3.0 cm (mean 1.8 cm; P < 0.05). The IIEF-EF score also improved in patients in the PG (by a mean of 5 points). Mild AEs occurred in 43% of patients, such as local discomfort and glans numbness. CONCLUSION: The use of the Penimaster PRO PTD, a non-invasive treatment, should be offered to patients with stable PD for 3 consecutive months before performing any corrective surgery, as this provided a significant reduction in the curvature, an increase in penile length and a significant improvement of the symptoms and bother induced by PD.

NH4(+) triggers the release of astrocytic lactate via mitochondrial pyruvate shunting.

Neural activity is accompanied by a transient mismatch between local glucose and oxygen metabolism, a phenomenon of physiological and pathophysiological importance termed aerobic glycolysis. Previous studies have proposed glutamate and K(+) as the neuronal signals that trigger aerobic glycolysis in astrocytes. Here we used a panel of genetically encoded FRET sensors in vitro and in vivo to investigate the participation of NH4(+), a by-product of catabolism that is also released by active neurons. Astrocytes in mixed cortical cultures responded to physiological levels of NH4(+) with an acute rise in cytosolic lactate followed by lactate release into the extracellular space, as detected by a lactate-sniffer. An acute increase in astrocytic lactate was also observed in acute hippocampal slices exposed to NH4(+) and in the somatosensory cortex of anesthetized mice in response to i.v. NH4(+). Unexpectedly, NH4(+) had no effect on astrocytic glucose consumption. Parallel measurements showed simultaneous cytosolic pyruvate accumulation and NADH depletion, suggesting the involvement of mitochondria. An inhibitor-stop technique confirmed a strong inhibition of mitochondrial pyruvate uptake that can be explained by mitochondrial matrix acidification. These results show that physiological NH4(+) diverts the flux of pyruvate from mitochondria to lactate production and release. Considering that NH4(+) is produced stoichiometrically with glutamate during excitatory neurotransmission, we propose that NH4(+) behaves as an intercellular signal and that pyruvate shunting contributes to aerobic lactate production by astrocytes.

Systematic review and meta-analysis on the efficacy and tolerability of mirabegron for the treatment of storage lower urinary tract symptoms/overactive bladder: Comparison with placebo and tolterodine.

A systematic review and meta-analysis was carried out to evaluate the efficacy and safety of mirabegron 50 mg and 100 mg in the treatment of storage lower urinary tract symptoms/overactive bladder in comparison with a placebo and tolterodine 4 mg. A total of 491 articles were collected and eight randomized studies were identified as eligible for this meta-analysis. Overall, eight trials were included in the meta-analysis evaluating 10 248 patients. Mirabegron at both doses of 50 mg and 100 mg, and and tolterodine 4 mg were significantly associated with the reduction of incontinence episodes per 24 h, reduction of mean number of micturitions per 24 h, increase of voided volume and reduction of urgency episodes per 24 h, compared to a placebo. Both mirabegron 50 mg and mirabegron 100 mg were associated with a significant reduction of nocturia episodes when compared with a placebo. Conversely, tolterodine 4 mg did not prove to be more effective than a placebo in the reduction of nocturia episodes. Furthermore, mirabegron 50 mg showed a slightly, but significantly, better efficacy than tolterodine 4 mg in the improvement of nocturia episodes. Mirabegron 50 mg and mirabegron 100 mg shared the same risk of overall treatment-emergent adverse events rate with the placebo. Otherwise, tolterodine 4 mg was associated with a significantly greater risk than the placebo. However, mirabegron 100 mg showed a slight trend toward an increased risk of hypertension (odds ratio 1.41; P = 0.08) and cardiac arrhythmia (odds ratio 2.18; P = 0.06). Mirabegron is an effective treatment for patients with storage lower urinary tract symptoms/overactive bladder, providing a reduction of incontinence, urgency and frequency; an improvement of voided volume with a slight, but statistically, significant improvement of nocturia; with a good safety profile. These findings should be considered for the treatment planning of patients with storage lower urinary tract symptoms/overactive bladder.

Near-critical GLUT1 and Neurodegeneration.

Recent articles have drawn renewed attention to the housekeeping glucose transporter GLUT1 and its possible involvement in neurodegenerative diseases. Here we provide an updated analysis of brain glucose transport and the cellular mechanisms involved in its acute modulation during synaptic activity. We discuss how the architecture of the blood-brain barrier and the low concentration of glucose within neurons combine to make endothelial/glial GLUT1 the master controller of neuronal glucose utilization, while the regulatory role of the neuronal glucose transporter GLUT3 emerges as secondary. The near-critical condition of glucose dynamics in the brain suggests that subtle deficits in GLUT1 function or its activity-dependent control by neurons may contribute to neurodegeneration. © 2017 Wiley Periodicals, Inc.

Channel-mediated lactate release by K⁺-stimulated astrocytes.

Excitatory synaptic transmission is accompanied by a local surge in interstitial lactate that occurs despite adequate oxygen availability, a puzzling phenomenon termed aerobic glycolysis. In addition to its role as an energy substrate, recent studies have shown that lactate modulates neuronal excitability acting through various targets, including NMDA receptors and G-protein-coupled receptors specific for lactate, but little is known about the cellular and molecular mechanisms responsible for the increase in interstitial lactate. Using a panel of genetically encoded fluorescence nanosensors for energy metabolites, we show here that mouse astrocytes in culture, in cortical slices, and in vivo maintain a steady-state reservoir of lactate. The reservoir was released to the extracellular space immediately after exposure of astrocytes to a physiological rise in extracellular K(+) or cell depolarization. Cell-attached patch-clamp analysis of cultured astrocytes revealed a 37 pS lactate-permeable ion channel activated by cell depolarization. The channel was modulated by lactate itself, resulting in a positive feedback loop for lactate release. A rapid fall in intracellular lactate levels was also observed in cortical astrocytes of anesthetized mice in response to local field stimulation. The existence of an astrocytic lactate reservoir and its quick mobilization via an ion channel in response to a neuronal cue provides fresh support to lactate roles in neuronal fueling and in gliotransmission.

The Impact of Central Obesity on Storage Luts and Urinary Incontinence After Prostatic Surgery.

In the developed and developing countries, the overall prevalence of central obesity in the elderly men is growing. In addition, the progressive aging of male population increased the possibilities of coexisting morbidities associated with obesity such as lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE) or to prostate cancer (PCa) needing primary treatment, including radical prostatectomy (RP), which can further adversely affect the quality of life. Simple and radical prostatectomy are the most common surgical procedures in urologic unit all over the world for BPE and PCa, respectively. After both interventions, patients can present bothering storage LUTS that can worsen all the other clinical outcomes. Preset study will review the role of central obesity as a risk factor for storage LUTS or urinary incontinence, after prostatic surgery for BPE or PCa.

Effects of tadalafil once daily or on demand versus placebo on time to recovery of erectile function in patients after bilateral nerve-sparing radical prostatectomy.

PURPOSE: We report time to erectile function (EF)-recovery data from a multicenter, randomized, double-blind, double-dummy, placebo-controlled trial evaluating tadalafil started after bilateral nerve-sparing radical prostatectomy (nsRP). METHODS: Patients ≤68 years were randomized post-nsRP 1:1:1 to 9-month double-blind treatment (DBT) with tadalafil 5 mg once daily (OaD), 20 mg tadalafil on demand ("pro-re-nata"; PRN), or placebo, followed by 6-week drug-free washout (DFW) and 3-month open-label OaD treatment. Secondary outcome measures included Kaplan-Meier estimates of time to EF-recovery (IIEF-EF ≥ 22) during DBT (Cox proportional hazard model adjusting for treatment, age, and country). RESULTS: A total of 423 patients were randomized to tadalafil OaD (N = 139), PRN (N = 143), and placebo (N = 141); 114/122/155 completed DBT. The proportion of patients achieving IIEF-EF ≥22 at some point during DBT with OaD, PRN, and placebo was 29.5, 23.9, and 18.4 %, respectively. DBT was too short to achieve EF-recovery (IIEF-EF ≥ 22) in >50 % of patients; median time to EF-recovery was non-estimable. Time for 25 % of patients to achieve EF-recovery (95 % CI) was 5.8 (4.9, 9.2) months for OaD versus 9.0 (5.5, 9.2) and 9.3 (9.0, 9.9) months for PRN and placebo, respectively. Showing a significant overall treatment effect (p = 0.038), the probability for EF-recovery was significantly higher for OaD versus placebo [hazard ratio (HR); 95 % CI 1.9; 1.2, 3.1; p = 0.011], but not for PRN versus placebo (p = 0.140). Of 57 OaD patients (41.0 %) with ED improved (by ≥1 IIEF-EF severity grade) at the end of DBT, 16 (28.1 % of 57) maintained this improvement through DFW and 27 (47.4 %) declined but maintained improvement from baseline after DFW. CONCLUSIONS: Data suggest that the use of tadalafil OaD can significantly shorten the time to EF-recovery post-nsRP compared with placebo.

Non-preferential fuelling of the Na(+)/K(+)-ATPase pump.

There is abundant evidence that glycolysis and the Na(+)/K(+)-ATPase pump are functionally coupled, and it is thought that the nature of the coupling is energetic, with glycolysis providing the ATP that fuels the pump. This notion has been instrumental to current models of brain energy metabolism. However, structural and biophysical considerations suggest that the pump should also have access to mitochondrial ATP, which is much more abundant. In the present study, we have investigated the source of ATP that fuels the Na(+) pump in astrocytes, taking advantage of the high temporal resolution of recently available FRET nanosensors for glucose, lactate and ATP. The activity of the Na(+) pump was assessed in parallel with the Na(+)-sensitive dye SBFI AM (Na(+)-binding benzofuran isophthalate acetoxymethyl ester). OXPHOS (oxidative phosphorylation) inhibition resulted in bulk ATP depletion and a 5-fold stimulation of glycolytic flux, in spite of which Na(+) pumping was inhibited by 90%. Mathematical modelling of ATP dynamics showed that the observed pump failure is inconsistent with preferential fuelling of the Na(+) pump by glycolytic ATP. We conclude that the nature of the functional coupling between the Na(+) pump and the glycolytic machinery is not energetic and that the pump is mainly fuelled by mitochondrial ATP.

Acute phase Peyronie's disease management with traction device: a nonrandomized prospective controlled trial with ultrasound correlation.

INTRODUCTION: Outcome data of penile traction therapy (PTT) for the acute phase (AP) of Peyronie's disease (PD) have not been specifically studied. AIM: The aim of this study was to assess the effectiveness of a penile extender device for the treatment of patients with AP of PD. METHODS: A total of 55 patients underwent PTT for 6 months and were compared with 41 patients with AP of PD who did not receive active treatment ("no intervention group" [NIG]). MAIN OUTCOMES MEASURES: Pre- and posttreatment variables included degree of curvature, penile length and girth, pain by 0-10 cm visual analog scale (VAS), erectile function (EF) domain of the International Index of Erectile Function questionnaire, Erection Hardness Scale, Sexual Encounter Profile 2 question, and penile sonographic evaluation (only patients in the intervention group). RESULTS: The mean curvature decreased from 33° at baseline to 15° at 6 months and 13° at 9 months with a mean decrease 20° (P < 0.05) in the PTT group. VAS score for pain decreased from 5.5 to 2.5 after 6 months (P < 0.05). EF and erection hardness also improved significantly. The percentage of patients who were not able to achieve penetration decreased from 62% to 20% (P < 0.03). In the NIG, deformity increased significantly, stretched flaccid penile length decreased, VAS score for pain increased, and EF and erection hardness worsened. PTT was associated with the disappearance of sonographic plaques in 48% of patients. Furthermore, the need for surgery was reduced in 40% of patients who would otherwise have been candidates for surgery and simplified the complexity of the surgical procedure (from grafting to plication) in one out of every three patients. CONCLUSIONS: PTT seems an effective treatment for the AP of PD in terms of pain reduction, penile curvature decrease, and improvement in sexual function.

[Sexual dysfunction secondary to urethral stricture and urethroplasty]. / Disfunciones sexuales secundarias a la estenosis uretral y a la uretroplastia.

OBJECTIVES: Urethral stenosis is a complex pathology that severely affects the quality of life of patients who suffer it. There are multiple therapeutic options, the main objective of which is to eliminate obstruction and improve symptoms, and consequently maintain or improve the quality of life of the patient. The objective of this article is to perform a systematic review of the literature with the aim to evaluate the results regarding the sexual sphere after urethral surgery. METHODS: We performed a bibliographic search in PubMed, identifying studies that analyzed the results in sexual function after various types of urethroplasties. Preference have been given to those articles evaluating sexual function both preoperative and postoperative, to determine the degree of involvement conditioned by surgery. Fourteen articles have been selected, including those making reference to sexual function (sexual desire, erectile and ejaculatory function). RESULTS: A total of 14 studies were selected to perform the analysis; they were divided into two groups depending of the perspective they have to evaluate results: Use of validated tests for data collection before and after surgery and a second group analyzing more qualitative features of the stenosis making the evaluation of results this way. Site of stenosis is not uniformly distributed in these articles, with predominance of those performing anterior urethra surgery. They have a comprehensive analysis of the various features that may affect directly or indirectly the result of the operation both in the short and long term. CONCLUSIONS: Most articles conclude that specific standardized tools are necessary for this type of pathology, with the aim of obtain results that are more adjusted to urethral surgery. Patient perception of the results of urethroplasty is a parameter that has gained great importance lately. Globally the results of postoperative sexual function are very satisfactory, mainly in young patients. It is important to globally analyze the results and surgical techniques currently in use with the aim to minimize deleterious effects on sexual function; moreover taking into account that the objective of surgery is to try to improve the patient's quality of life.

Penile prosthesis implantation is safe and effective in Peyronie's disease patients with and without erectile dysfunction.

Penile prosthesis (PP) is the mainstay of treatment in Peyronie's disease (PD) with co-existent refractory erectile dysfunction (ED). This study aimed to assess the clinical outcomes of patients who underwent PP as the first-line surgical treatment in PD without ED. A total of 636 patients underwent PP for PD from 2012 to 2022, but only 168 patients who underwent PP as first-line surgical management for PD with or without ED were included in the study. The mean (SD) age of 168 patients was 56.3 years (12.4). The mean curvature of the "PD with ED" group and the "PD without ED" group were 38.2 (5.6) degrees and 42.2 (5.9) degrees. The median (IQR) follow-up was 56.0 months (34.5- 61.4). Most (86.9%) patients underwent 3-piece inflatable PP. An important finding is that 33 patients (19.6%) without ED had undergone PP. Mechanical failure requiring revision surgery was less common in the 'without ED' group than in the ED group (6.8% vs. 10.2%, p 0.04). Most PD patients without ED (87.9%, 29/33) and with ED (88.9%, 120/135) were "satisfied" after PP implantation at six months, as defined by a score of ≥4 on a 5-point Likert scale. If surgery is offered in PD, PP may be considered a safe and effective first-line surgical treatment regardless of the ED, given the acceptable complications and high satisfaction rates. However, this new concept warrants further research.

Adherence to initial PDE-5 inhibitor treatment: randomized open-label study comparing tadalafil once a day, tadalafil on demand, and sildenafil on demand in patients with erectile dysfunction.

INTRODUCTION: Phosphodiesterase type 5 (PDE-5) inhibitor treatment for erectile dysfunction (ED) is frequently discontinued; adherence may vary depending on the initial regimen. AIM: To evaluate the effects of initiating treatment with tadalafil once a day (OaD), tadalafil on demand (pro re nata [PRN]), or sildenafil PRN on treatment adherence. METHODS: In this multicenter, open-label study, men (≥ 18 years) with ED, naïve to PDE-5 inhibitors, were randomized (1:1:1) to tadalafil 5 mg OaD, tadalafil 10 mg PRN, or sildenafil 50 mg PRN. An 8-week randomized treatment (RT) period (dose adjustment possible) was succeeded by 16 weeks of pragmatic treatment (switches between PDE-5 inhibitors allowed). MAIN OUTCOME MEASURES: Treatment adherence was measured as time to discontinuation of RT (any cause), estimated by Kaplan-Meier product-limit method. Treatment-group differences were estimated as hazard ratio (HR; Cox proportional hazards). RESULTS: Seven hundred seventy patients (mean age 53 years) were randomized to tadalafil OaD (N = 257), tadalafil PRN (N = 252), and sildenafil PRN (N = 261). Kaplan-Meier estimates for patients discontinuing RT were 52.2, 42.0, and 66.7%, respectively. Median time to discontinuation of RT was significantly longer for tadalafil OaD and PRN (130 and >168 days) compared with sildenafil (67 days) (HR [97.5% confidence interval]: 0.66 [0.51, 0.85] and 0.49 [0.37, 0.65]; P < 0.001). Reasons for discontinuation with significant differences between groups (P < 0.05) included "lack of efficacy (duration of erection)" (sildenafil 9.2% vs. tadalafil OaD 4.3%, PRN 2.8%), "time constraints due to short window of action" (sildenafil 4.2% vs. tadalafil OaD 0%, PRN 0.4%), and "feel medication controls my sexual life" (sildenafil 2.7% vs. tadalafil OaD 0%). No between-group differences were found in International Index of Erectile Function-Erectile Function domain change from baseline to end of RT (least squares mean: 9.4-10.0, P = 0.359) or discontinuations due to adverse events (1.2-1.6%). The most common adverse event (≥ 4%) was headache. CONCLUSIONS: ED patients assigned to tadalafil OaD or PRN adhered significantly longer to initial treatment than patients assigned to sildenafil PRN. Improvement of erectile function and safety profiles were similar in all three treatment groups.

[Patient with testosterone deficit syndrome after radical prostatectomy]. / Paciente con síndrome de déficit de testosterona tras prostatectomía radical.

Testosterone Deficiency Syndrome is associated with age. Recent studies advocate for the safety of hormonal treatment with testosterone in patients with history of Prostate Cancer (PC) ,once disease-free survival is confirmed. A total of five publications describe 110 patients treated with testosterone replacement therapy, having a history of PC, who had undergone radical prostatectomy (RP). Only one patient had biochemical recurrence during replacement therapy. Testosterone replacement therapy must be indicated in selected patients with history of low risk localized prostate cancer treated satisfactorily who are symptomatic and have good oncological control. The testosterone levels to achieve should be the minimum effective to obtain a symptomatic response. Adequate information on the benefits and potential risks must be understood and accepted by the patient.