Published data suggest that compared to APOE3, APOE4 could increase the risk of neurodegeneration via higher cerebrovascular permeability. We recently proposed the concept that brain endothelial cell APOE is protective for cerebrovascular function in a genotype specific manner, APOE3 > APOE4, and therefore APOE4 brain endothelial cells may be predisposed to dysfunction during aging and disease. In addition to mechanistic implications, our concepts and methods may have therapeutic applications; identifying compounds that protect APOE4 brain endothelial cells. The goal of this proof-of-concept study was to determine whether APOE4 brain endothelial cells can be used as a phenotypic compound screen. Previously we found that APOE4 brain endothelial cells are particularly sensitive to lipopolysaccharide- (LPS) induced permeability disruption when measured by trans endothelial cell electrical resistance (TEER) in vitro. Here, we followed the NIH Assay guidance manual to convert our in vitro assay to a phenotypic screen. We scaled the isolation protocol, selected conditions for the min, mid and max signals, statistically validated the phenotypic assay, screened compounds, validated hits and tested the top hits in vivo. We scaled the isolation protocol and selected conditions for min (0.8µg/ml LPS), mid (10 µM sildenafil/LPS) and max conditions (vehicle). Our final protocol met the reproducibility acceptance criteria for a statistically validated assay. We then screened a subset of ~ 900 molecules from the TargetMol Bioactive Library and identified two main groups compounds. The first group disrupted APOE4 brain endothelial cells as they were toxic or lowered TEER and many inhibited mTOR. The second group protected against LPS-induced TEER reduction. With relatively stringent criteria we identified 33 protective compounds that are grouped into those that inhibit growth factor receptor signaling and a range of intracellular signaling pathways. We compared the most active compounds and selected four to test in vivo. Tadalafil (PDE5 inhibitor), vorinostat (HDAC inhibitor), CCT196969 (raf inhibitor) and SGI-7079 (AXL inhibitor) mitigated acute LPS-induced cerebrovascular dysfunction in mice that express APOE4. Overall, our data supports the potential of our in vitro screen to identify compounds that prevent LPS-induced dysfunction in APOE4 brain endothelial cells.

The combined treatment with TOP-V122, a dual-acting NO-releasing PDE-5 inhibitor, and ionizing irradiation as a novel therapeutical strategy for colorectal carcinoma.

The AOPP-cNOS relay: A Redox-Metabolic pathway in the lung-brain axis of pulmonary hypertension and neurovascular injury.

Intracavernosal injections (ICI) are commonly used to treat erectile dysfunction in men following radical prostatectomy (RP). Predictors of treatment success are still unclear. Our objective was to explore the relationship between various clinical and pathologic parameters and the achievement of satisfactory erections with ICI following RP. This is a prospective study of men following RP with bilateral neurovascular bundle preservation who experienced erectile dysfunction refractory to treatment with phosphodiesterase type 5 inhibitors (PDE5I) at a minimum of six months after surgery. Three escalating dosages of TRIMIX were used consecutively (5 mg papaverine, 0.5 mg phentolamine, 10 mcg alprostadil; 10 mg papaverine, 1 mg phentolamine, 20 mcg alprostadil; 17 mg papaverine, 1 mg phentolamine, and 30 mcg alprostadil). Erection Hardness Scale (EHS) and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) were used for functional assessments. Thirty-four patients were stratified by their EHS scores and Trimix dosages: low-dose full responders (n=12), intermediate-dose full responders (n=10), high-dose partial responders (n=7), high-dose failures (n=5). Twenty-nine patients (85%) reported on satisfactory erectile function with ICI. The ICIQ-SF scores were the only parameter that correlated significantly with successful erectile response, with median scores of 0, 3.5, 11, and 16 for the respective groups above (p=0.001). Univariate logistic regression demonstrated a significant association between ICIQ-SF scores and partial or non-response (odds ratio 1.3, 95% confidence interval 1.1-1.5, p=0.002). ICI is an efficient therapy for achieving satisfactory erections following RP in PDE5I-resistant men. Sustainable urinary incontinence is a strong predictor of poor response to therapy.

Abstract Erectile dysfunction (ED) is one of the most frequent and distressing complications after radical prostatectomy (RP), significantly impairing patients’ quality of life and intimate relationships. Penile rehabilitation (PR) aims to preserve erectile tissue integrity, prevent fibrosis, and facilitate early functional recovery by restoring oxygenation to the corpora cavernosa. Current PR strategies include oral phosphodiesterase type 5 inhibitors (PDE5is), intracavernosal injections, and vacuum erection devices, used alone or in combination. Adjunctive options, such as low‐intensity shockwave therapy, stem cell therapy, and platelet‐rich plasma, are currently under investigation. Despite widespread use, there is no standardized PR protocol, and evidence remains mixed regarding optimal timing, dosage, and duration. This review summarizes contemporary and emerging PR modalities, highlighting evidence‐based principles, patient selection, and integration of preoperative counseling to set realistic expectations. Psychosocial support, partner involvement, and multidisciplinary collaboration are essential to maximize adherence and recovery. Future research should prioritize high‐quality randomized controlled trials to define standardized, evidence‐based PR protocols tailored to individual risk profiles and preferences, ultimately improving functional recovery and quality of life after RP.

Exploring the relationship between adherence and outcomes in pulmonary arterial hypertension: A retrospective cohort study in the United States.

Erectile dysfunction (ED), a condition affecting nearly 150 million men worldwide, is expected to impact over 300 million by 2025. Phosphodiesterase type 5 inhibitors (PDE5Is) remain the first-line treatment for ED, yet a subset of patients exhibit inadequate responses. For these individuals, the inflatable penile prosthesis (IPP) offers an effective alternative, with the three-piece IPP being particularly favored for its high satisfaction and low complication rates. However, the challenge of optimal reservoir placement, particularly in the extraperitoneal space of Retzius (SOR), has prompted investigations into alternative approaches. SOR placement is associated with complications, such as injury to iliac vessels, bladder puncture, and bowel perforation. Various alternative sites have been proposed, including epigastric extraperitoneal, intraperitoneal (IP), high submuscular (HSM), and lateral retroperitoneal (LRP) positions, each aiming to mitigate these risks while improving patient outcomes. Comparative studies have shown that methods such as IP and HSM reduce the risk of vessel compression and bladder injury, often yielding higher satisfaction rates compared with SOR. However, each technique carries unique drawbacks, including risks of palpability, improper placement, and longer operative times. This review synthesizes current evidence on reservoir placement strategies, evaluates their advantages and limitations, and highlights crucial considerations for patient selection, providing a comprehensive overview of IPP implantation techniques and their evolving roles in the management of ED.

A rationale for PDE5 inhibitors as a cardiovascular risk mitigation strategy in postmenopausal women.

P0172 Targeting the Stromal Switch: Single-cell profiles implicate the cGMP-PKG pathway in driving fibrosis and cancer progression in Ulcerative Colitis

Phosphodiesterase type 5 inhibitors (PDE5Is) are widely prescribed for erectile dysfunction; however, growing evidence indicates that their pharmacological effects extend beyond urological indications and involve multiple organ systems. This narrative review aims to synthesize and critically evaluate current evidence on the systemic effects of PDE5 inhibitors across cardiovascular, renal, neurological, and urological domains, as well as emerging therapeutic indications. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science for studies published up to May 2024, including preclinical studies, clinical trials, observational studies, systematic reviews, and meta-analyses. The reviewed evidence demonstrates that PDE5 inhibitors are associated with reduced cardiovascular morbidity and mortality, improvements in cardiac and pulmonary hemodynamics, preservation of renal function in diabetic populations, potential neuroprotective effects against cognitive decline and ischemic stroke, and symptomatic improvement in benign prostatic hyperplasia and lower urinary tract symptoms. Additional benefits have been reported in conditions characterized by vascular dysfunction, such as angina pectoris and Raynaud’s phenomenon. Overall, PDE5 inhibitors represent a pharmacologically versatile drug class with clinically relevant systemic effects beyond erectile dysfunction, supporting their potential role as adjunctive therapies in broader disease management, although further well-designed randomized controlled trials are needed to inform clinical guidelines.

Phosphodiesterase type-5 inhibitors (PDE5is) are used for the treatment of erectile dysfunction (ED) and have potential cardioprotective effects. The impacts of PDE5is on cardiovascular parameters, which may be associated with the occurrence and progression of subclinical cardiovascular diseases, remain uncertain. In this study, we evaluated the effects of PDE5is on vascular parameters. Randomized controlled trials (RCTs) that compared the effects of PDE5is and placebo on vascular parameters and were published from 1998 to 2022 were identified from PubMed, Scopus and Web of Science. Mean differences (MDs) with 95% confidence intervals (CIs) were pooled. A sensitivity analysis was conducted to confirm the robustness of the pooled results. The keywords that were searched in the databasesare as follows: ((systolic blood pressure) OR (SBP) OR (diastolic blood pressure) OR (DBP) OR (mean arterial pressure) OR (MAP) OR (Pulse Wave Velocity) OR (PWV) OR (intima-media thickness) OR (cIMT) OR (augmentation Index) OR (AI) OR (FMD) OR (flow-mediated dilation) OR (reactive hyperemia index) OR (RHI) OR (Endothelial microparticles) OR (EMP) OR (EPCs) OR (Endothelial Progenitor Cells) OR (PSV) OR (peak systolic velocity)) AND ((PDE5 Inhibitors) OR (PDE5i) OR (Sildenafil) OR (Vardenafil) OR (Tadalafil) OR (Lodenafil) OR (Udenafil) OR (Avanafil)). Sixty-three studies involving 3242 subjects were included. Overall, PDE5is decreased systolic blood pressure (MD: -2.80mmHg, 95% CI: -4.24, -1.37, P < 0.001), diastolic blood pressure (MD: -1.80mmHg, 95% CI: -2.37, -1.22, P < 0.001), carotid intima‒media thickness (MD: -0.01mm, 95% CI: -0.02, -0.01, P < 0.001), and pulse wave velocity (MD: -0.75cm/s, 95% CI: -1.01, -0.49, P < 0.001). In addition, PDE5is increased the peak systolic velocity (MD: 3.70cm/s, 95% CI: 3.52, 3.88, P < 0.001), flow-mediated dilation (MD: 2.47%, 95% CI: 1.24, 3.71, P < 0.001), concentration of endothelial progenitor cells (MD: 475.29 cells/mL, 95% CI: 51.38, 899.20, P = 0.03), and concentration of endothelial microparticles (MD: 4.86%, 95% CI: 0.65, 9.07, P = 0.02). However, the effects of PDE5is on the augmentation index, brachial artery diameter and reactive hyperemia index were not statistically significant. Compared with the placebo, PDE5is improved vascular parameters, indicating the potential of PDE5is for treating subclinical cardiovascular diseases. Further research is needed to confirm the role of the improvement on vascular parameters by PDE5isin preventing and treating cardiovascular diseases. The present study protocol was reviewed and approved by PROSPERO. The title is "Associations between PDE5is and vascular parameters: A systematic review and meta-analysis" (https://www.crd.york.ac.uk/PROSPERO/) (Reg. No. CRD42023387924).

Phosphodiesterase type 5 inhibitors (PDE-5i) are the common oral medications prescribed for the treatment of erectile dysfunction (ED). In recent years, health supplements have gained popularity as alternative options to prescription PDE-5i. However, concerns have emerged regarding the adulteration of these products with undeclared synthetic PDE-5i or their analogues, posing significant health risks. In this study, a rapid, simple, and efficient analytical method for the determination of PDE-5i was developed and validated using a liquid chromatography&amp;ndash;tandem mass spectrometry system (LC-MS/MS) for the rapid detection of these compounds in health supplement products collected in Hanoi. The method demonstrated excellent linearity (R&amp;sup2; &amp;ge; 0.999). The limits of detection (LOD) and quantification (LOQ) were 1.5 &amp;micro;g/kg and 5.0 &amp;micro;g/kg for sildenafil, tadalafil, and vardenafil, and 15 &amp;micro;g/kg and 50 &amp;micro;g/kg for the remaining PDE-5i. Recoveries ranged from 80.9% to 113% with relative standard deviations (%RSD) below 15%. The validated procedure was applied to 24 real-world samples, and 13 of them were found to contain PDE-5i. Further comprehensive investigations involving larger sample sizes and additional PDE-5i compounds are necessary to better assess adulteration practices and potential health risks.

Phosphodiesterase type-5 inhibitors (PDE5i) are the first-line therapy for erectile dysfunction (ED), offering high efficacy and favorable safety profiles. However, data on how long PDE5i remain effective before the need for penile prosthesis (PP) surgery are limited. This study evaluates the duration from PDE5i initiation to PP surgery and identifies predictors of this interval. We conducted a retrospective review of patients with ED who initiated PDE5i therapy and subsequently underwent PP surgery between January 2019 and August 2022. Clinical characteristics, laboratory results, and duration of PDE5i use were extracted from hospital records. A total of 98 patients were included, with a mean age of 56.1 ± 11.5 years and a mean body mass index (BMI) of 29.8 ± 4.4 kg/m². Comorbidities were present in 88.8 % of patients, including diabetes mellitus (75.5 %), hypertension (54.1 %), and smoking (31.6 %). The mean time from PDE5i initiation to PP surgery was 34.9 ± 24.8 months (≈ 2.9 years). Lower testosterone levels were associated with earlier surgery, while comorbidities were not. The average duration of PDE5i use prior to PP surgery was approximately three years. Lower testosterone levels may predict earlier surgical intervention, whereas comorbidities did not show a significant association. These findings may assist clinicians in counseling patients and planning treatment strategies.

Neuroinflammation and oxidative stress contribute significantly to cognitive decline, a hallmark of neurodegenerative diseases such as Alzheimer's disease (AD). Addressing cognitive decline is a critical medical need, and phosphodiesterase-5 inhibitors (PDE5Is) may offer a promising solution. This meta-analysis highlights the anti-inflammatory and antioxidant actions of PDE5Is, which may help counter neuroinflammation and oxidative stress in neurodegenerative diseases including AD. We reviewed over 1,258 studies and considered 34 preclinical rodent studies of inflammation or oxidative stress. Quantitative data on biomarkers such as Tumor necrosis factor alpha (TNF-α), Interleukin 1 beta (IL-1β), IL-6, NF-κB, IL-10, Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), Glutathione (GSH), Malondialdehyde (MDA), Myeloperoxidase (MPO), and caspase-3 was extracted and analyzed using a random-effects model. Study quality was evaluated with a modified CAMARADES checklist, and heterogeneity was assessed using the I2 statistic. PDE5Is treatment significantly lowered pro-inflammatory cytokines and oxidative stress markers, while boosting the levels of critical anti-inflammatory and antioxidant molecules. The pooled standardized mean differences (SMDs) indicated treatment efficacy for nearly all biomarkers. Notably, the studies on Alzheimer's models confirmed similar therapeutic benefits in reducing amyloid burden and enhancing cognitive outcomes. With a strong safety profile and ability to modulate Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Nuclear erythroid-related factor 2 (Nrf2) pathways, PDE5Is offer promising neuroprotective potential. Thus, repurposing PDE5Is may develop new disease-modifying therapies for Alzheimer's, making clinical investigation crucial.

INTRODUCTION. Sexual activity is an important component of the overall quality of life. Erectile dysfunction (ED) has recently been considered an epidemic of the 21st century and is an extremely common pathology that has been observed throughout all periods of the development of our civilization. The frequency of ED is increasing significantly every year, which is associated with an increase in the population of men suffering from ED. There are many models of ED treatment, of which metabolic therapy occupies an important place. MATERIALS AND METHODS. A systematic analytical review of the scientific literature on the effect of the amino acids arginine and citrulline on erectile function was conducted for the period 2015–2025 in the databases PubMed, Scopus, Google Scholar, ISSWSH. RESULTS AND DISCUSSION. The main pathophysiological mechanism leading to the formation of ED is a violation of cavernous hemodynamics. The key factors that shape the occurrence of an erection include hemodynamic changes, relaxation of smooth muscles and the regulatory effect of neurotransmitters, among which nitric oxide (NO) is the most influential universal secondary messenger. A decrease in the ability of endothelial cells to produce NO is most often the main cause of ED, as it causes impaired blood flow and a decrease in various functions of the male genitalia. During sexual stimulation, its concentration is released in the endothelium of blood vessels and smooth muscle cells, which leads to dilation of the vessels of the penis, the corpus cavernosum and the onset of an erection. The amino acid arginine is a metabolic substrate for the synthesis of the primary mediator NO. Arginine acts on the vascular system and participates in the regulation of testosterone synthesis, and a decrease in its level is a risk factor for the development of vascular pathology of the genital organs. One of the possible ways to eliminate endothelial dysfunction is to enhance the synthesis of NO by adding exogenous L-arginine. To date, it is believed that phosphodiesterase type 5 inhibitors (PDE5 inhibitors) are the first-line therapy for most men with ED. Certain groups of patients who have a burdened health condition in the form of severe diabetes mellitus, arterial hypertension, secondary hypogonadism are difficult to treat exclusively with PDE5 inhibitors, taking into account systemic disorders of endothelial function. In the event of such clinical circumstances, the search for new drugs becomes particularly promising. Oral administration of L-arginine in high doses causes a significant subjective improvement in sexual function in men with organic ED only under conditions of reduced excretion or production of NO. The benefits of L-arginine in the treatment of various male sexual dysfunctions are confirmed by a number of scientific studies, and the intake of L-citrulline increases the level of L-arginine in the blood serum and has a positive effect on the synthesis of nitric oxide, as a key metabolite of the endothelial function of the cavernous tissue of the penis. L-citrulline is converted to L-arginine in the kidneys, which justifies the need for its addition in ED as a donor of the L-arginine/NO/cGMP pathway. The use of L-citrulline improves the ratio of intra-abdominal pressure/microfibrillar pressure, the ratio of body weight/collagen, and increases the level of NOx. In Ukraine, the drug VALARGIN PLUS is registered — a dosage form containing L-arginine — 1500 mg and L — citrulline — 1500 mg (mg). CONCLUSIONS. Based on the above, it can be assumed that the use of L-arginine in combination with L-citrulline in the treatment of erectile dysfunction in men is a more effective method than monotherapy with L-arginine. The combination of L-arginine and L-citrulline (Valagrin Plus) is an effective component of the complex treatment of patients with erectile dysfunction.

ObjectivesThe study examined the impact of varying prescription requirements for phosphodiesterase-5 inhibitors (PDE-5is) on the management of erectile dysfunction (ED) in men.MethodsA survey involving 10,000 men from Germany, Norway, Poland, and Switzerland was conducted using the International Index of Erectile Function Questionnaire to identify men with ED and interview them regarding their treatment and experiences. The use of PDE-5is by men without ED was also investigated.ResultsThe proportion of PDE-5i users with ED was higher in Norway and Poland (over-the-counter availability) and Switzerland (prescribed by pharmacist) than that in Germany (doctor’s prescription required). Across all countries, men seeking to buy PDE-5is from pharmacies were advised to consult a doctor. The use of black market channels for purchasing PDE-5is was minimal in regions allowing non-prescription availability. The non-medical use was uncommon in all regions.ConclusionThe need for a prescription for PDE-5is may hinder seeking treatment for ED and detecting underlying conditions. Therefore, PDE-5is should be approved as prescription-free medicines to improve the management of ED and to encourage men’s engagement with the healthcare system.

IntroductionPhosphodiesterase-5 (PDE5) inhibitors, commonly prescribed for erectile dysfunction, may exhibit immunomodulatory properties by reducing myeloid-derived suppressor cell activity and enhancing T-cell responses. This study evaluated the association between PDE5 inhibitor use and overall survival (OS) in male-predominant solid organ malignancies.MethodsMale-predominant solid tumors were identified using male-to-female incidence ratio ≥3:1 in SEER database: prostate, bladder, colon, esophageal, hypopharyngeal, laryngeal, tonsillar, and testicular cancers. Using the TriNetX Research Network, we compared male patients prescribed PDE5 inhibitors within 6 months of cancer diagnosis to those without PDE5 exposure. Propensity score matching (PSM) was performed on demographic, clinical, and oncologic variables. OS was assessed in a combined pan-cancer cohort, stratified by overall stage, and subgroups of included cancers. Kaplan-Meier survival analyses were conducted for 1-, 3-, and 5-year OS from diagnosis.ResultsAfter PSM, 108,630 patients were included in each arm of the pan-cancer analysis. PDE5 inhibitor exposure was associated with significantly improved OS at 1, 3, and 5 years compared with controls (5-year OS 93.8% vs 86.6%; HR, 0.42 [95% CI, 0.41–0.44]). Stratified analyses demonstrated significantly improved OS across all four stages, with hazard ratios ranging from 0.40 to 0.57. Subgroup analyses by tumor site likewise showed statistically significant improvement in OS for every included cancer type, with hazard ratios ranging from 0.35 to 0.70.ConclusionsPDE5 inhibitor use was consistently associated with improved OS across all male-predominant cancers, including in stage-stratified analyses. These findings support further investigation into the potential role of PDE5 inhibitors in cancer outcomes.

Abstract Introduction Nitric Oxide boosting supplements improve circulation by increasing cGMP. PDE-5 inhibitors work by blocking PDE- 5, which increases NO mediated blood flow to the penis by enhancing cyclic GMP. There is limited objective data on the synergistic effects of NO boosting dietary supplements and PDE-5 inhibitors. The NO boosting dietary supplement used in this study consists of L-citrulline, Red Beet Root extract, Panax Ginseng Root Extract, and Muira Puama Extract. The kidneys convert L-citrulline into Arginine, which produces NO that relaxes blood vessels and improves blood flow. Beetroot extract has a high nitrate content, which the body converts into NO. Nighttime erections can be measured and provide an objective indicator of erectile health. Objective We investigated whether ingesting a NO boosting dietary supplement and Sildenafil 40 mg one hour before sleep can improve nighttime erectile function compared to Sildenafil 40 alone by using the TechRing by FirmTech to measure penile pressure while sleeping. Methods 22 men completed the study. Average age 55. Average SHIM score 18.1. A single tablet of the NO boosting dietary supplement contains 750 mg L-Citrulline, 65 mg Muira Puama Extract 4:1, Red Beet Root extract 45mg 4:1, Panax Ginseng Root Extract 35mg 4:1. This supplement is commercially available as AFFIRM. Participants wore the TechRing during sleep to measure nighttime erectile function. The TechRing uses two sensors and an AI interface to measure the firmness and duration of erections. The protocol was a 2-day washout period with no ejaculation, ED medications, or supplements. Days 1&amp;2 participants ingested Sildenafil 40 mg one hour before bedtime and wore the TechRing while sleeping. Days 3&amp;4 participants ingested two supplement tablets and Sildenafil 40 mg 1 hour before sleep and wore the TechRing. We calculated the area under the curve per hour of sleep (AUC/hr) as reported by the TechRing as a measure of erectile activity. Results The AUC/hr of the men taking Sildenafil 40mg with no dietary supplement was 87, and the AUC/hr on the two days when participants took Sildenafil 40mg and the supplement was 117. The difference in means was 30 (34% increase), and the p-value was 0.00004. (t=5.219) The mean number of erections per night was 3.25 with Sildenafil 40mg and no dietary supplement, and 3.87 with Sildenafil 40mg and the dietary supplement. There was a slight significant difference in the number of erections per night (p-value 0.034 (t=2.285)). No side effects were self-reported from taking the dietary supplement or Sildenafil 40mg at bedtime. Conclusions The combination of Sildenafil 40mg and a NO boosting dietary supplement increased the duration and intensity of nighttime erections compared to Sildenafil 40 mg alone as measured by the TechRing. This NO boosting dietary supplement improves genital circulation at night. This NO boosting supplement may also be synergistic with Sildenafil and improve genital circulation during awake sexual activity. Many men who take PDE-5 inhibitors will get side effects. Taking a Nitric Oxide boosting dietary supplement may boost the effectiveness of a PDE-5 inhibitor without generating side effects that can limit the dose. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: AFFIRM Science, FirmTech

Abstract Introduction RARP is a common procedure carried out for patients with prostate cancer. Erectile function (EF) recovery is known to be significantly lower following NNS RARP compared to nerve-sparing procedure.​ There is a lack of research evaluating the efficacy of post-operative treatment options-such as phosphodiesterase type 5 inhibitors (PDE5i), vacuum erection devices (VED), and intracavernosal injections (ICI)-in patients who have undergone NNS RARP.​ Objective Outline efficacy rates of various ED treatments after NNS- RARP including: PDE5i Vitaros (intraurethral alprostadil) ICI VED Methods Retrospective andrology follow-up after NNS RARP at a high-volume referral centre between 2018 and 2024 (7 years). Exclusion: Prior prostate cancer treatment (radiotherapy or focal therapy) or any degree of nerve sparing. Data collected: comorbidities, histological parameters, and baseline and postoperative SHIM scores. Efficacy was defined as erections sufficient for intercourse, based on patient self-report assessed via clinical notes. Results A total of 404 patients met the inclusion criteria, with a median age of 65 years (IQR: 35–49), a median BMI of 28, and a mean follow-up period of 14 months (IQR: 5–39). The median pre-operative SHIM score was 14 (IQR: 6–22), dropping to 5 postoperatively. Treatment Outcomes 1. PDE5 Inhibitors (Sildenafil 100 mg / Tadalafil 20 mg) Treated: 301 patients Response: 5 patients (1.6%) 2. Vacuum Erection Device (VED) Treated: 319 patients Response: 24.5% resumed sexual activity 3. Vitaros (Intraurethral Alprostadil) Treated: 87 patients Response: 12 patients (13.8%) 4a. ICI – Alprostadil Treated: 159 patients Response: 35% resumed sexual activity Side Effects: Pain (29), Prolonged erections not amounting to priapism (4) 4b. ICI – Invicorp (Aviptadil/Phentolamine) Treated: 42 patients Response: 50% 5. Penile Implants Implanted in: 28 patients (6.9% of cohort) Conclusions This study highlights the limited effectiveness of PDE5 inhibitors after non-nerve-sparing robotic-assisted prostatectomy, with response rates of just 1.6%. Vacuum erection devices offered moderate success in a quarter of motivated patients, while intracavernosal injections delivered the highest efficacy. Early use of second-line therapies-alone or in combination with VED-may improve outcomes. These findings reinforce the need for timely counselling on ICI, earlier implant consideration, and tailoring penile rehabilitation protocols to nerve-sparing status, as one size does not fit all. Disclosure No

Abstract Introduction Phosphodiesterase type 5 inhibitors (PDE5i) remain the first-line treatment for erectile dysfunction (ED); however, their efficacy is inconsistent across patient populations, and their use may be limited by contraindications and side effects. Vacuum erection devices (VEDs) are the second most commonly used alternative, though they are often associated with discomfort, bruising, and variable user satisfaction. Furthermore, objective data on erection firmness and duration with VED use remain limited Objective This study aims to evaluate the impact of the Vaxaid Hydropump on erection firmness and duration, both during sexual activity and nocturnal episodes. Methods We conducted a prospective observational study of men aged 30–75 years with moderate erectile dysfunction (ED), defined by an international Index of Erectile Function (IIEF) score between 8-21. Demographic and comorbidity data was recorded. Participants were provided with the Vaxaid Hydropump and the FirmTech TechRing wearable device. The TechRing recorded data on nocturnal and sexual erections, independent of Hydropump use, specifically firmness, and duration. Baseline data was analyzed using descriptive statistics. Results Preliminary baseline data from our 47 men cohort showed a mean age of 55 ± 10.7 years. Participants experienced an average of 2.3 nocturnal erections per night, with a median of 2.3 and a range of 0-5 episodes. The mean duration was 51 ± 19 minutes, with a median of 47 minutes (IQR: 14-113 minutes). The average firmness of nocturnal erections was 7.2 ± 0.9. In contrast, erections during sexual activity showed lower average firmness and greater variability (6.32 ± 4.05). The mean duration of erections during sexual activity was 28 ± 29 minutes, with a median of 20 minutes (IQR: 0–151 minutes) Conclusions Preliminary data from this study highlight differences between types of erectile episodes, suggesting that nocturnal erections are more consistent in firmness, duration, and frequency compared to those occurring during sexual activity. This distinction may reflect differing psychological and physiological influences on erectile function. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Endo, Marius, Besins, Firmtech, BathMate