EF Domain Research Articles

Comparing the efficacy of tadalafil and tamsulosin for managing erectile dysfunction and lower urinary tract symptoms in prostate brachytherapy patients: a prospective study

IntroductionAdverse events, such as erectile dysfunction (ED) and lower urinary tract symptoms (LUTS), are significant concerns in prostate cancer (PCa) patients treated with Iodine 125 (I-125) low-dose rate (LDR) prostate brachytherapy (PB). Alpha antagonists and phosphodiesterase-5 inhibitors are used to manage these events. The present study compared the efficacy of low-dose tadalafil with that of tamsulosin for concomitant ED and LUTS in PCa patients treated with I-125 LDR PB. Materials and methodsOne hundred and seventeen patients who received PB for low- or intermediate-risk localized PCa were analyzed. They were randomized into two groups, one receiving tamsulosin (N = 58) and the other receiving low-dose tadalafil (N = 59) immediately after PB. Sexual and urinary functions were assessed at various time points post-PB using questionnaires and objective measurements. The primary endpoint was sexual function measured by the International Index of Erectile Function-15 (IIEF-15) EF domain scores 6 months after PB. Secondary endpoints were sexual function measured by total IIEF-15 scores and Erection Hardness Scores 6 months after PB. The exploratory endpoint was the LUTS status 6 months after PB. ResultsNo significant differences were observed in baseline characteristics between the two groups. Tadalafil exerted stronger effects on sexual function, particularly erection hardness, than tamsulosin. No significant differences were observed in the management of LUTS between both treatments. ConclusionLow-dose tadalafil and tamsulosin may manage LUTS equally after PB. Low-dose tadalafil may contribute to the maintenance of erectile function, particularly erection hardness, after PB; therefore, it is a viable option for patients with baseline erectile function.

(343) Predictors of Corporo-venocclusive Dysfunction (CVOD) in Men with Bilateral Nerve-sparing Radical Prostatectomy (RP)

Abstract Introduction Nerve-sparing status (NSS) during RP is a significant predictor of erectile function recovery (EFR). Poor nerve sparing is associated with collagenization of cavernosal smooth muscle and CVOD development with typically poor response to PDE5 inhibitors (PDE5i) and intracavernosal injection therapy (ICI). Objective This study aimed to define factors predictive of CVOD in men with bilateral NS RP. Methods Study population consisted of (i) men who underwent bilateral NS (defined by the surgeon using an institutional grading system) RP (ii) with poor response to PDE5i and ICI (iii) ≥2 years post-RP (iv) who underwent penile duplex Doppler ultrasound (DUS) (v) using a vasoactive agent redosing schedule. CVOD diagnosis was made with end-diastolic velocity (EDV) values ≥5 cm/sec bilaterally. ADT and radiation therapy were exclusions. We used multivariable modeling to define factors predictive of CVOD. Factors included in the model: patient age, history of diabetes, history of obstructive sleep apnea, number of vascular comorbidities, baseline EF, peri-RP total testosterone (T) level, and total T at DUS (within 3 months). Results 201 men with a mean age of 66 ± 7 years. 25% of the patients reported 3 or more vascular comorbidities, 17% had diabetes, 36% obstructive sleep apnea, 39% were current or former smokers. Mean baseline PSA and pre-RP total T was 6.7 ± 6 ng/mL and 410 ± 211 ng/dL, respectively. Median baseline EFD score was 24 (13, 29). 49% of the men had an erection less than penetration rigidity during the DUS procedure with a mean total dose administered of 87 ± 21 units of trimix. 69% received 100 units. CVOD was diagnosed in 76%. Mean total T at DUS was 386 ± 177 ng/dL. 32% had low T. Significant predictors of CVOD after RP in men with BL NSS were: OSA (OR = 3.8, 95% CI = 1.7-8.7), ≥ 3 vascular comorbidities (OR = 5.0, 95% CI = 1.7-14.8), age at the time of DUS (per 10 years increase, OR = 1.9, 95% CI = 1.2-3.0), and pre-RP EF domain score (per 1 unit increase, OR = 0.93, 95% CI 0.88-0.98). There was a signal that in a larger sample size, diabetes may be a significant predictor of CVOD in this group of patients (OR = 2.7, 95% 0.9-8.0). Conclusions Baseline clinical comorbidities pre-RP have a significant impact on EFR post-RP, in particular, the presence of venous leak. Despite BL NSS, older patients, men with OSA, higher number of comorbidities pre-RP, and lower pre-RP EF increased the likelihood of developing CVOD post-RP. Disclosure No

(122) Erectile Hemodynamics Asessment In ED Patients With Self-Diagnosed Post-finasteride syndrome (PFS)

Abstract Introduction Much debate exists regarding the concept of PFS and its etiology. There exists data suggesting abnormal erectile hemodynamic alterations in this population. Objective This analysis was performed to define erectile hemodynamics in this population. Methods Patients attending the sexual medicine clinic at our institution presenting with (i) new onset ED after commencement of 5-ARI (ii) 5-ARI use specifically for hair loss (iii) with no prior ED history (iv) presenting ≥6 months after cessation of 5-ARI (v) and with at least 3 months use of 5-ARI (finasteride). All completed the IIEF EF domain questionnaire. B-mode assessment was conducted at 15MHz. Duplex ultrasound (PDDU) was conducted using a vasoactive agent-redosing schedule using trimix. On PDDU, a best quality erection (BQE) (equivalent to the best erection obtainable at home without erectogenic medication) was required for inclusion. Redosing was conducted if the patient failed to obtain a BQE up to a maximum of three doses. The criteria for normalcy on DUS included a peak systolic velocity (PSV) >30cms/s and an end-diastolic velocity (EDV) <5 cms/s. Results 141 men were included in the analysis. Mean patient age was 31±12 (18-42) years. All had used finasteride 1mg. Median vascular risk factor (VRF) number = 1 (0,1). Median duration of 5-ARI exposure = 16 (4, 46) months. Median duration off 5-ARI at first presentation to clinic = 11 (6, 28) months. No patients had ED prior to 5-ARI use. One third developed ED only after cessation of finasteride, at a mean duration off finasteride of 6±3 months. Median IIEF EFD score at presentation = 14 (6,18). Median (range) number of injections needed for BQE sufficiently suitable for DUS measurement was 2 (1, 3). Overall, mean PSV and EDV values were 60±18cm/s and 1.5±1.5 cm/s respectively. 29% required phenylephrine reversal before discharge from clinic. Conclusions These data suggest that hemodynamic alterations are not present in men complaining of ED with self-diagnosed PFS. Disclosure No

Fractionation of executive functions in adolescents from Iran: invariance across age and socioeconomic status

AbstractExecutive functions (EFs) are cognitive skills that regulate thoughts and behavior. The seminal EF unity and diversity theoretical framework proposes the existence of three correlated EF latent domains (inhibition, updating, and switching) that become distinguishable from a certain moment during adolescence, but it is unclear how age and socioeconomic status (SES) affect these abilities. Here, we assessed 407 9-15-year-old Iranians of variable SES using an open-access battery of executive function tests that includes two tasks of each EF domain and allows for sociocultural adaptations regarding language and stimuli. Various EF model configurations proposed in the literature were tested (one, two and three EF latent factor, nested and bifactor-S-1 models) using confirmatory factor analyses. In addition, to explore the unbiased effects of age and SES, we performed invariance testing (across age and SES) using multiple indicators multiple causes (MIMIC) model to the best fitting model solution. The three-correlated EF factor model had the best fit and was mostly invariant across age and SES, with all three EF latent traits improving with age, while SES exerted only minimal positive effects on shifting and updating. We concluded that the three separable EF domains, found in adults and adolescents of other ages from different populations, can already be detected from the beginning of adolescence when culturally and psychometrically appropriate EF tasks are used. Additionally, these abilities continue to improve with age and are little affected by SES, suggesting that the unity and diversity framework is useful to study the cross-country generality of EF development.

Ca2+ -induced structural changes and intramolecular interactions in N-terminal region of diacylglycerol kinase alpha.

Diacylglycerol kinases (DGKs) are multi-domain lipid kinases that modulate the levels of lipid messengers, diacylglycerol, and phosphatidic acid. Recently, increasing attention has been paid to its α isozyme (DGKα) as a potential target for cancer immunotherapy. However, little progress has been made on the structural biology of DGKs, and a detailed understanding of the Ca2+ -triggered activation of DGKα, for which the N-terminal domains likely play a critical role, remains unclear. We have recently shown that Ca2+ binding to DGKα-EF induces conformational changes from a protease-susceptible "open" conformation in the apo state to a well-folded one in its holo state. Here, we further studied the structural properties of DGKα N-terminal (RVH and EF) domains using a series of biophysical techniques. We first revealed that the N-terminal RVH domain is a novel Ca2+ -binding domain, but the Ca2+ -induced conformational changes mainly occur in the EF domain. This was corroborated by NMR experiments showing that the EF domain adopts a molten-globule like structure in the apo state. Further analyses using SEC-SAXS and NMR indicate that the partially unfolded EF domain interacts with RVH domain, likely via hydrophobic interactions in the absence of Ca2+ , and this interaction is modified in the presence of Ca2+ . Taken together, these results present novel insights into the structural rearrangement of DGKα N-terminal domains upon binding to Ca2+ , which is essential for the activation of the enzyme.

MP21-02 PREDICTORS OF CORPORO-VENOCCLUSIVE DYSFUNCTION (CVOD) IN MEN WITH BILATERAL NERVE-SPARING RADICAL PROSTATECTOMY (RP)

You have accessJournal of UrologyCME1 May 2022MP21-02 PREDICTORS OF CORPORO-VENOCCLUSIVE DYSFUNCTION (CVOD) IN MEN WITH BILATERAL NERVE-SPARING RADICAL PROSTATECTOMY (RP) Jose M. Flores, Carolyn A. Salter, Nicole Benfante, Elizabeth Schofield, and John P. Mulhall Jose M. FloresJose M. Flores More articles by this author , Carolyn A. SalterCarolyn A. Salter More articles by this author , Nicole BenfanteNicole Benfante More articles by this author , Elizabeth SchofieldElizabeth Schofield More articles by this author , and John P. MulhallJohn P. Mulhall More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002554.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Nerve-sparing status (NSS) during RP is a significant predictor of erectile function recovery (EFR). Poor nerve sparing is associated with collagenization of cavernosal smooth muscle and CVOD development with typically poor response to PDE5 inhibitors (PDE5i) and intracavernosal injection therapy (ICI). This study aimed to define factors predictive of CVOD in men with bilateral NS RP. METHODS: Study population consisted of (i) men who underwent bilateral NS (defined by the surgeon using an institutional grading system) RP (ii) with poor response to PDE5i and ICI (iii) ≥2 years post-RP (iv) who underwent penile duplex Doppler ultrasound (DUS) (v) using a vasoactive agent redosing schedule. CVOD diagnosis was made with end-diastolic velocity (EDV) values ≥5 cm/sec bilaterally. ADT and radiation therapy were exclusions. We used multivariable modeling to define factors predictive of CVOD. Factors included in the model: patient age, history of diabetes, history of obstructive sleep apnea, number of vascular comorbidities, baseline EF, peri-RP total testosterone (T) level, and total T at DUS (within 3 months). RESULTS: 201 men with a mean age of 66 ± 7 years. 25% of the patients reported 3 or more vascular comorbidities, 17% had diabetes, 36% obstructive sleep apnea, 39% were current or former smokers. Mean baseline PSA and pre-RP total T was 6.7 ± 6 ng/mL and 410 ± 211 ng/dL, respectively. Median baseline EFD score was 24 (13, 29). 49% of the men had an erection less than penetration rigidity during the DUS procedure with a mean total dose administered of 87 ± 21 units of trimix. 69% received 100 units. CVOD was diagnosed in 76%. Mean total T at DUS was 386 ± 177 ng/dL. 32% had low T. Significant predictors of CVOD after RP in men with BL NSS were: OSA (OR = 3.8, 95% CI = 1.7-8.7), ≥ 3 vascular comorbidities (OR = 5.0, 95% CI = 1.7-14.8), age at the time of DUS (per 10 years increase, OR = 1.9, 95% CI = 1.2-3.0), and pre-RP EF domain score (per 1 unit increase, OR = 0.93, 95% CI 0.88-0.98). There was a signal that in a larger sample size, diabetes may be a significant predictor of CVOD in this group of patients (OR = 2.7, 95% 0.9-8.0). CONCLUSIONS: Baseline clinical comorbidities pre-RP have a significant impact on EFR post-RP, in particular, the presence of venous leak. Despite BL NSS, older patients, men with OSA, higher number of comorbidities pre-RP, and lower pre-RP EF increased the likelihood of developing CVOD post-RP. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e327 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jose M. Flores More articles by this author Carolyn A. Salter More articles by this author Nicole Benfante More articles by this author Elizabeth Schofield More articles by this author John P. Mulhall More articles by this author Expand All Advertisement PDF DownloadLoading ...

Efficacy of Intracavernosal Injections of 50-Unit Versus 100-Unit Doses of AbobotulinumtoxinA (Masport®) in Vasculogenic Erectile Dysfunction with Phosphodiesterase Type 5 Inhibitors Resistant

Background: We aimed to evaluate the safety and efficacy of 50-unit dose against 100-unit dose of intracavernosal injection (ICI) of AbobotulinumtoxinA (BTX-A) (Masport®) in patients with vascular erectile dysfunction (ED) resistant to first-line therapies, including phosphodiesterase type 5 inhibitors (PDE5I). Methods: In this double-blind randomized controlled trial (RCT), 40 patients with ED resistant to PDE5I were randomly divided into two groups: ICI of a single dose of Masport® 50 units and single dose of 100 units. Peak systolic velocity (PSV) confirmed arterial insufficiency vascular disorder. For all patients, International Index of Erectile Function (IIEF), Sexual Health Inventory for Men (SHIM), and Erection Hardness Score (EHS) questionnaires were completed. Six weeks after the treatment, the subjects were re-examined. Results: Our results showed an acceptable clinical efficacy and safety of ICI of Masport® six weeks after injection. No systemic complications in patients were seen. Three patients complained of brief penile pain shortly after injection, but there were no other local complications. The increase in mean PSV in the 100-unit group due to treatment was significant (P-value < 0.0001). Also, there was a significant difference between the two groups of 50- and 100-unit (P-value < 0.0001). In addition, the increase in mean IIEF-EF, SHIM score, and EHS due to treatment was significant between the two groups. For the 100-unit group, P-value < 0.0001 and the difference between the two groups was also significant (P-value < 0.0001), which indicated a better response to treatment in the 100-unit group. The mean increase of IIEF score (EF domain) was 4.3 (mean IIEF: 9.4 and 13.7 after and before, respectively) in the 100-unit group and (mean IIEF: 8.1 and 9.1 after and before, respectively) in the 50-unit group. Conclusions: The results of this study showed that ICI of AbobotulinumtoxinA, especially at a dose of 100 units, in patients with refractory vasculogenic ED is safe and effective in improving sexual function and ultrasound indices.

Serum concentrations of dihydrotestosterone are associated with symptoms of hypogonadism in biochemically eugonadal men

PurposeSymptoms of hypogonadism are often reported by subjects with normal serum testosterone (T) levels. We aimed to assess the association between clinical symptoms in andrological outpatients and sex steroids levels.MethodsThis is a retrospective cross-sectional cohort study in an Academic clinic and research unit. International Index of Erectile Function (IIEF, EF domain) and Aging Males Symptoms scale (AMS) questionnaires were completed by 635 and 574 men, respectively (mean age: 47.3 ± 13.9 and 47.4 ± 13.8 years, p = 0.829), free of interfering medications with complaints possibly related to hypogonadism.ResultsSerum total/free T as well as dihydro-T (DHT) was associated with IIEF-EF and AMS scores in the overall population using univariate analyses. Multivariate approaches revealed DHT concentrations in subjects with normal T levels (n = 416, Total T > 12 nmol/L) to be significant predictors of AMS scores. A 0.1 nmol/l serum DHT increase within the eugonadal range was associated with a 4.67% decrease in odds of having worse symptoms (p = 0.011). In men with biochemical hypogonadism (Total T < 12 nmol/L), total and free T rather than DHT were associated with AMS results. This association was not found for IIEF-EF scores. Indirect effects of age and BMI were seen for relations with hormone concentrations but not questionnaire scores.ConclusionDHT can be associated with symptoms of hypogonadism in biochemically eugonadal men. Serum DHT measurement might be helpful once the diagnosis of hypogonadism has been ruled out but should not be routinely included in the primary diagnostic process.

Structure of transmembrane prolyl 4-hydroxylase reveals unique organization of EF and dioxygenase domains

Prolyl 4-hydroxylases (P4Hs) catalyze post-translational hydroxylation of peptidyl proline residues. In addition to collagen P4Hs and hypoxia-inducible factor P4Hs, a third P4H—the poorly characterized endoplasmic reticulum–localized transmembrane prolyl 4-hydroxylase (P4H-TM)—is found in animals. P4H-TM variants are associated with the familiar neurological HIDEA syndrome, but how these variants might contribute to disease is unknown. Here, we explored this question in a structural and functional analysis of soluble human P4H-TM. The crystal structure revealed an EF domain with two Ca2+-binding motifs inserted within the catalytic domain. A substrate-binding groove was formed between the EF domain and the conserved core of the catalytic domain. The proximity of the EF domain to the active site suggests that Ca2+ binding is relevant to the catalytic activity. Functional analysis demonstrated that Ca2+-binding affinity of P4H-TM is within the range of physiological Ca2+ concentration in the endoplasmic reticulum. P4H-TM was found both as a monomer and a dimer in the solution, but the monomer–dimer equilibrium was not regulated by Ca2+. The catalytic site contained bound Fe2+ and N-oxalylglycine, which is an analogue of the cosubstrate 2-oxoglutarate. Comparison with homologous P4H structures complexed with peptide substrates showed that the substrate-interacting residues and the lid structure that folds over the substrate are conserved in P4H-TM, whereas the extensive loop structures that surround the substrate-binding groove, generating a negative surface potential, are different. Analysis of the structure suggests that the HIDEA variants cause loss of P4H-TM function. In conclusion, P4H-TM shares key structural elements with other P4Hs while having a unique EF domain.

Renal Transplantation Improves Erectile Function in Patients with End-Stage Renal Disease: A Systematic Review and Meta-Analysis.

Erectile dysfunction has a lower prevalence in renal transplant recipients compared to dialysis patients. Despite this observation, the effect of renal transplantation on erectile function remains unknown. We aimed to assess the role of renal transplantation on erectile function and to determine potential factors improving or deteriorating erectile dysfunction. We conducted a systematic review and random effects meta-analysis of observational studies comparing erectile function preoperatively and postoperatively in renal transplant recipients (PROSPERO ID: CRD42020189580). Records reporting relevant outcomes were identified through search of PubMed®, Embase®, Cochrane Library and Scopus® databases from inception to September 2020. Judgment of the strength of evidence was performed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We included 20 studies with 1,695 renal transplant recipients. At postoperative evaluation the number of patients with erectile dysfunction was reduced (RR 1.21, 95% CI 1.02-1.45, I2=88%). Renal transplant recipients reported an improvement in erectile function (RR 2.53, 95% CI 1.44-4.44, I2=90%) and the mean International Index of Erectile Function score increased by 3.04 points (95% CI 0.63-5.45, I2=96%) after renal transplantation. These effects were not demonstrated in the sensitivity analysis. In individuals reporting severe erectile dysfunction, no favorable effect of renal transplantation was observed (RR 1.51, 95% CI 0.85-2.68, I2=33%). For all outcomes the strength of evidence was considered low or very low due to methodological concerns and high heterogeneity among the included studies. Renal transplantation improves erectile function and the risk of erectile dysfunction reduces postoperatively compared to preoperatively. However, evidence on the matter is mostly based on low quality data. More studies with standardized outcomes are needed to validate and strengthen our findings.

N-terminal truncation of VC0395_0300 protein from Vibrio cholerae does not lead to loss of diguanylate cyclase activity

The bacterial secondary messenger bis-(3′,5′)-cyclic-dimeric-guanosine monophosphate (c-di-GMP) has been implicated in the pathogenesis of Vibrio cholerae, due to its significant role in regulating the virulence, biofilm formation and motility of the host organism. The VC0395_0300 protein from V. cholerae, possessing a GGEEF sequence has been established as a diguanylate cyclase (DGC) capable of catalyzing the conversion of two GTP molecules to form cyclic-di-GMP. This in turn, plays a crucial role in allowing the organism to adopt a dual lifestyle, thriving both in human and aquatic systems. The difficulty in procuring sufficient amounts of homogenous soluble protein for structural assessment of the GGDEF domain in VC0395_0300 and the lack of soluble protein yield, prompted the truncation into smaller constructs (Sebox31 and Sebox32) carrying the GGDEF domain. The truncates retained their diguanylate cyclase activity comparable to the wild type, and were able to form biofilms as well. Fluorescence and circular dichroism spectroscopy measurements revealed that the basic structural elements do not show significant changes in the truncated proteins as compared to the full-length. This has also been confirmed using homology modeling and molecular docking of the wild type and truncates. This led us to conclude that the truncated constructs retain their activity in spite of the deletions in the N terminal region. This is supportive of the fact that DGC activity in GGDEF proteins is predominantly dependent on the presence of the conserved GGD(/E)EF domain and its interaction with GTP.

A Change in Domain Cooperativity Drives the Function of Calnuc.

With the increasing incidence of neurodegenerative disorders, there is an urgent need to understand the protein folding process. Examining the folding process of multidomain proteins remains a prime challenge, as their complex conformational dynamics make them highly susceptible to misfolding and/or aggregation. The presence of multiple domains in a protein can lead to interaction between the partially folded domains, thereby driving misfolding and/or aggregation. Calnuc is one such multidomain protein for which Ca2+ binding plays a pivotal role in governing its structural dynamics and stability and, presumably, in directing its interactions with other proteins. We demonstrate differential structural dynamics between the Ca2+-free and Ca2+-bound forms of calnuc. In the absence of Ca2+, full-length calnuc displays equilibrium structural transitions with four intermediate states, reporting a sum of the behavioral properties of its individual domains. Fragment-based studies illustrate the sequential events of structure adoption proceeding in the following order: EF domain followed by the NT and LZ domains in the apo state. On the other hand, Ca2+ binding increases domain cooperativity and enables the protein to fold as a single unit. Single-tryptophan mutant proteins, designed in a domain-dependent manner, confirm an increase in the number of interdomain interactions in the Ca2+-bound form as compared to the Ca2+-free state of the protein, thereby providing insight into its folding process. The attenuated domain crosstalk in apo-calnuc is likely to influence and regulate its physiologically important intermolecular interactions.

P-02-14 Intra-Urethral Alprostadil Gel Usage in Male Sexual Dysfunction Restores Not Only Erectile Performances but Improves Also the Conjunct Premature Ejaculation

To assess the extensive satisfaction of the intra-urethral utilization of Alprostadil gel in men having both erectile dysfunction (ED) and premature ejaculation (PE). A cohort of 67 men with ED and PE (Gr. A), taking Alprostadil gel by intra-urethral way admission, as a frequency of 3-4/week, before each intimate encounter, was assessed at the recruitment (V1) and after 4 follow-up weeks (V2). They were compared to a 50 men control group, taking Sildenafil 100mg/tb. (Gr. B). Instruments: ED = IIEF-5, ≤ 20 points; PE (short Intravaginal Ejaculation Latency Time - IELT) ≤ 3 minutes (ISSM, 2014); Overall Satisfaction (OS) = EF domain from the IIEF. Global Assessment Question (GAQ): % of “yes” (Giuliano et al., 2008). IIEF-5 at V1: Gr. A = 12.72 ± 3.8, Gr. B = 11.96 ± 4.07 vs. V2: Gr. A = 19.56 ± 2.18, Gr. B = 20.21 ± 1.67; P = 0.5; IELT at V1: Gr. A = 2.47 (2 min. and 28 sec.), Gr. B = 2.15 ± (2 min. and 17 sec.) vs. V2: Gr. A = 6.78 (6 min. and 47 sec.) ± 2.33, Gr. B = 3.33 (3 min. and 20 sec.); P < 0.001. OS at V1 Gr. A = 6.81 ± 1.18, Gr. B = 6.62 ± 0.87 vs. V2: Gr. A = 12.33 ± 3.11, Gr. B = 8.22; P < 0.05. GAQ at V1: Gr. A = 14 subjects (20.89%), Gr. B = 12 subjects (24%) vs. V2: Gr. A = 54 subjects (80.6%); Gr. B = 24 subjects (48%); P(V2) < 0.005.

P-02-17 Efficacy of Low-Intensity Extracorporeal Shockwaves Treatment in Erectile Dysfunction

Evaluate efficacy of LISWT to improve erectile function in ED patients. 20 consecutive non-vascular mild ED patients (mean IIEF-15 EF domain = 19,4 ± 2.1); mean age 56.3 years, range 39-68) underwent 6 LISWT sessions, each session delivering 1500-4000 shocks. For 2 weeks before, during the treatment period and four weeks after LISWT patients were asked to refrain form PDE5i use. Once PDE5i treatment was re-introduced (Tadalafil 2.5 mg daily), patients were evaluated at 1, 2 and 6 months follow-up by using IIEF-15 erectile function domain and EHS questionnaires. Penile color-Doppler parameters in the flaccid state were evaluated before, during and after treatment according with standardized procedure. Collected data were analyzed using T-test and Wilcoxon test. No statistically significative difference in IIEF-15 EF domain, EHS and flow parameters was found when baseline and follow-up parameters were compared. EF-domain showed an improvement at both 2 and 6 months follow-up visit (mean 19.4 ± 2.1 vs 14.3 ± 1.3, p= 0.06) compared with baseline. Moreover, percentage of patients showing EF improvement increased during the treatment: 25 % at 6th treatment session vs 43.75 % at 2 months follow-up and 62.5 % at 6 months follow-up, respectively. Compared with baseline, EHS score improved in 7/20 patients at the end of the treatment session, in 8/16 patients at 1 months follow-up, and in 8/16 at 2 and 6 months follow-up (p < 0.05).

MP78-15 POST-SSRI SEXUAL DYSFUNCTION (PSSD): TEN YEAR RETROSPECTIVE CHART REVIEW

You have accessJournal of UrologySexual Function/Dysfunction: Evaluation II (MP78)1 Apr 2020MP78-15 POST-SSRI SEXUAL DYSFUNCTION (PSSD): TEN YEAR RETROSPECTIVE CHART REVIEW Ahad Waraich*, Channing Clemons, Roma Ramirez, Jessica Yih, Sue Goldstein, and Irwin Goldstein Ahad Waraich*Ahad Waraich* More articles by this author , Channing ClemonsChanning Clemons More articles by this author , Roma RamirezRoma Ramirez More articles by this author , Jessica YihJessica Yih More articles by this author , Sue GoldsteinSue Goldstein More articles by this author , and Irwin GoldsteinIrwin Goldstein More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000964.015AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Post-SSRI Sexual Dysfunction (PSSD) is a poorly understood, iatrogenic, distressing, multidimensional sexual health condition that occurs in young patients and includes ED, hypoactive sexual desire disorder (HSDD), orgasmic dysfunction, and/or decreased genital sensation, that despite discontinuation of SSRI/SNRI agents, persists > 6 mo. We wished to better understand PSSD, the frequency/severity of symptoms, and the results of diagnostic testing. METHODS: A retrospective review was performed of charts from 2009 to 2019. Patients reported their symptoms, completed the IIEF, and underwent a grayscale/Doppler ultrasound during pharmacological erection (15.4 MHz probe; Aixplorer® Ultrasound) and Quantitative Sensory Testing (QST) (vibration, hot and cold perception testing). RESULTS: 43 male patients (mean age 31, range 18 – 59) met the criteria for PSSD; 4% of the male patients seen during this period. The most common symptom was ED in 93% (40/43). The mean IIEF-EF score was 12.9/30. The most common EF domain score was consistent with severe ED 49% (16/33), followed by mild-moderate 24% (8/33), moderate 9% (3/33), and mild 9% (3/33). A total of 9% (3/33) had no ED. For ED patients who underwent grayscale/Doppler ultrasound, 79% (23/29) had varying degrees of erectile tissue inhomogeneity (hypo- and hyperechoic regions noted). The mean cavernosal artery PSV values were left 30.3 cm/sec and right 31.7 cm/sec. Concomitant sexual health concerns of HSDD, orgasmic dysfunction, and decreased genital sensation were noted in 86% (38/43), 72% (31/43), and 67% (29/43) of patients, respectively. For patients with orgasmic dysfunction and/or decreased genital sensation who underwent QST testing, 89% (25/28) had abnormal results. CONCLUSIONS: This series of PSSD patients examined clinically is larger than any in the peer-reviewed literature. Consistent with other reports on PSSD, our patients are young, have ED in most cases, and frequently have concomitant HSDD, poor orgasm and decreased genital sensation. New information includes the facts that 1) ED is most often severe, 2) erectile tissue inhomogeneity is common, consistent with erectile tissue fibrosis/decreased erectile tissue expandability as an underlying vascular ED pathophysiology, and 3) decreased genital sensation from neurological dysfunction is frequent in this population. Providers need to be aware that the persistent sexual health consequences following SSRI/SNRI discontinuation are significant and patients should be referred to sexual medicine specialists for management. Source of Funding: No funding. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1179-e1179 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ahad Waraich* More articles by this author Channing Clemons More articles by this author Roma Ramirez More articles by this author Jessica Yih More articles by this author Sue Goldstein More articles by this author Irwin Goldstein More articles by this author Expand All Advertisement PDF downloadLoading ...

Biochemical and structural analyses reveal that the tumor suppressor neurofibromin (NF1) forms a high-affinity dimer

Biochemical and structural analyses reveal that the tumor suppressor neurofibromin (NF1) forms a high-affinity dimer

Does Decision-Making Ability Predict HIV-Associated Neurocognitive Disorder?

Abstract Background Executive dysfunction (EF) in people living with HIV (PLWH) is well-established. However, decision-making, a key aspect of EF, is often overlooked in neurocognitive (NC) evaluations of PLWH. Poor decision-making can detrimentally impact PLWH by increasing risk of poor health outcomes. This study aimed to determine if including a decision-making task in NC evaluations might improve diagnostic formulations. Participants and Method This cross-sectional study included 90 PLWH (63 Latinx; 27 non-Latinx white) who were evaluated for HIV-Associated Neurocognitive Disorder (HAND) using established criteria, with the Wisconsin Card Sorting Test (WCST) and Trail Making Test Part B (TMTB) comprising the “traditional” EF domain. The Iowa Gambling Task (IGT) assessed decision-making. Demographically corrected T-scores were calculated for each test. The “traditional” EF tests were averaged into an EF domain T-score. The WCST, TMTB, and IGT were also averaged into a “new” EF+IGT domain T-score. Results The new EF+IGT domain T-score significantly predicted HAND diagnosis (R^2 = .14, p &amp;lt; .001). However, using hierarchical regression, the “traditional” EF domain (WCST and TMTB) also significantly predicted HAND (R^2 = .18, p &amp;lt; .001) and adding the IGT Total T-score did not contribute unique variance to the model (R^2 = .18, p &amp;lt; .001; R^2Δ &amp;lt; .001, pΔ = .92). Conclusions A new combined EF domain T-score that included decision-making was a significant predictor of HAND diagnosis. However, adding IGT Total Score did not enhance HAND diagnosis compared to “traditional” EF measurement, indicating that the “traditional” EF domain adequately informs HAND diagnosis. A limitation of this study was the small sample size. Given the important health implications of decision-making in PLWH, future research, with a larger sample size is warranted to better conceptualize how decision-making can be incorporated into diagnostic formulations for PLWH.

Comparison of impact of monopolar versus bipolar resection of the prostate on erectile function in patients with benign hyperplasia of the prostate

Introduction and ObjectiveThe incidence of erectile dysfunction (ED) after TURP for BPH is still debated. Current study aims at comparing the impact of monopolar and bipolar TURP on the sexual function of male patients with LUTS, using the IIEF EF-domain score (questions 1–5, 15) and to identify statistical risk factors associated with development of post-operative ED. Patients and methodsBetween April 2014 and May 2015, 102 patients underwent TURP for symptomatic BPH. Sixty on underwent TURP by the monopolar technique and 41 by the bipolar technique. Patients were assessed on the day before the surgery by IIEF and followed up 3 and 6 months postoperatively, using the same scoring system. ResultsOn a 6 month follow up,13 patients (22.4%) in the monopolar group and 12 (30%) in the bipolar group, experienced clinical change in their EF score. Among risk factors studied, only diabetes, intraoperative capsular perforation and preoperative use of PDE5I had a statistically significant impact on the EF score.No statistically significant difference in IIEF score and EF domain score was observed between the patients who underwent TURP by the monopolar technique, compared to those patients in which the bipolar one was used; whether at three months (p value 0.33) or at six months (p value 0.397). ConclusionNo statistical difference could be detected between monopolar and bipolar TURP, regarding the risk of developing post-operative ED. However, a higher incidence of ED should be anticipated in patients with DM, intraoperative capsular perforation and preoperative use of PDE5I.

Safety and efficacy of sildenafil citrate in treating erectile dysfunction in patients with combat-related post-traumatic stress disorder: A double-blind, randomized and placebo-controlled study

To evaluate the safety and efficacy of sildenafil citrate for treating erectile dysfunction (ED) in patients with combat related post-traumatic stress disorder (PTSD).Patients and methodsIn all, 266 combat-exposed war veterans with ED (aged 37–59 years) were recruited. They met the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for PTSD according to the Structured Clinical Interview for Patients, Investigator Version. The patients were also evaluated with the Clinician-Administered PTSD Scale, both to establish the diagnosis of PTSD and to measure symptom severity. Only patients with psychogenic ED were included in the study. The patients were randomly divided into a group of 133 who received 100 mg of on-demand sildenafil 0.75–2 h before sexual stimulation, and 133 who received placebo. Patients were asked to use ≥ 16 doses or attempts at home.ResultsSildenafil did not produce significantly and substantially greater improvement than placebo in each of the primary and secondary outcome measures (P = 0.08). A normal EF domain score (≥ 26) at endpoint was reported by 13 (9.8%), and 11 (8.3%) of patients on the sildenafil and placebo regimens, respectively (P = 0.09). Patients treated with sildenafil had no statistically significantly greater improvement in the five sexual function domains of the IIEF questionnaire than those treated with placebo (P = 0.08). The incidences of treatment-emergent adverse events were significantly greater in the sildenafil arm than in the placebo group (P = 0.01).ConclusionsSildenafil is no better than placebo in treating PTSD-emergent ED.Disclosure of interestThe author has not supplied his declaration of competing interest.

133 Grey-Scale Penile Ultrasound Findings in Young Men with Erectile Dysfunction (ED) Who Used Finasteride for Androgenic Alopecia: A Retrospective Review

ED has been reported following use of finasteride in young men with androgenic alopecia. Animal studies reveal erectile tissue fibrosis after exposure to 5 alpha reductase inhibitors. 8 men (mean age 32) met inclusion/exclusion criteria: potent prior to and developed ED since use of finasteride for androgenic alopecia; less than 40 years old without obvious cardiovascular risk factor exposure; underwent Grey-scale and color duplex Doppler ultrasound (Aixplorer 15.4 MHz transducer) during maximal pharmacologic erection, performed using axial B-mode imaging at multiple gains/multiple locations. Presence/absence of erectile tissue homogeneity or observation of hyperechoic/hypoechoic regions, presence/absence of cavernosal artery atherosclerosis, cavernosal artery diameter, and tunical thickness values were noted. Most patients completed: International Index of Erectile Function (IIEF), Sexual Distress Scale- Revised (SDS-R), Patient Heath Questionnaire (PHQ-9), Perceived Stress Scale (PSS) questionnaires. Patients used finasteride for mean 7.4 years. Other complaints were low libido (63%), orgasm dysfunction (50%), cognitive changes (50%), mood changes (50%). Dihydrotestosterone (DHT) blood test values were low/in lower tertile in 63%. On IIEF, EF domain scores were < 26/30, mean 15; mean scores for desire, orgasm, intercourse satisfaction, overall sexual satisfaction were 5/10, 7.7/10, 6.6/15, 3.2/10 respectively, with mean total IIEF score 37.3/75. SDS-R scores were abnormal with depression and stress noted in 71% and 86%. All 8 patients had lack of homogeneity with obvious hyperechoic/hypoechoic regions in erectile tissue consistent with mild to mild-moderate corporal erectile tissue fibrosis. Other Grey-scale measurements included: absent atherosclerosis in right/left cavernosal arteries, mean dorsal/ventral tunical thickness 1.3/1.2 mm; mean right/left cavernosal artery diameter 1.1/1.0 mm. Color duplex Doppler studies revealed mean right/left peak systolic velocity values 23.2/25.2 cm/sec, and mean right/left end diastolic velocity values 1.5/1.4 cm/sec.