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A range of drugs have a direct role in triggering ischaemic priapism. We aimed at identifying: a) which medications are associated with most priapism-reports; and, b) within these medications, comparing their potential to elicit priapism through a disproportionality analysis. The FDA Adverse Event Reporting System (FAERS) database was queried to identify those drugs associated the most with priapism reports over the last 5 years. Only those drugs being associated with a minimum of 30 priapism reports were considered. The Proportional Reporting Ratios (PRRs), and their 95% confidence intervals were computed. Out of the whole 2015-2020 database, 1233 priapism reports were identified, 933 of which (75.7%) were associated with 11 medications with a minimum of 30 priapism-reports each. Trazodone, olanzapine and tadalafil showed levels of disproportionate reporting, with a PRR of 9.04 (CI95%: 7.73-10.58), 1.55 (CI95%: 1.27-1.89), and 1.42 (CI95%: 1.10-1.43), respectively. Most (57.5%) of the reports associated with the phosphodiesterase type 5 inhibitors (PDE5Is) were related with concomitant priapism-eliciting drugs taken at the same time and/or inappropriate intake/excessive dosage. Patients taking trazodone and/or antipsychotics need to be aware of the priapism-risk; awareness among prescribers would help in reducing priapism-related detrimental sequelae; PDE5I-intake is not responsible for priapism by itself, when appropriate medical supervision is provided., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

A limited number of studies have described patients on finasteride showing findings which were consistent with Peyronie's disease (PD). We aimed to detect a pharmacovigilance signal of possible association between finasteride and PD-related clinical features. The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database was queried to identify the ten drugs which were associated the most with the adverse drug reactions (ADRs) recorded as "penile curvature" and/or "Peyronie's disease". A similar analysis, including the same drugs, was carried out for the EMA (European Medicines Agency) EudraVigilance (EV) database. Descriptive data have been analyzed, and Proportional Reporting Ratios (PRRs) have been computed against the other nine drugs of the database. Overall, 860 reports of "penile curvature" and/or "Peyronie's disease", were identified in the FAERS database, 214 of which (24.9%) were associated with finasteride. Most reports (56.9%) were submitted by healthcare professionals. Where a treatment-indication was stated, the vast majority of reports (176/210; 83.8%) were associated with androgenetic alopecia. The outcome of most ADRs was "serious" (82.2%), with 96 ADRs resulting in levels of permanent disability. For 97/214 individual cases, penile curvature/PD reports were not part of a syndromic cluster suggestive of post-finasteride syndrome (PFS). The PRR resulted 6.6 (95% CI: 5.6-7.8) and 11.8 (95% CI: 9.08-15.33), respectively, in the FAERS and in the EV databases. Notwithstanding the related limitations and biasing factors of pharmacovigilance studies based on spontaneous reporting, the PRR values here identified should be interpreted as strong signals of disproportionality. These findings, per se, are however not useful to confirm any causal association. Clinical studies are needed to investigate on the possible role for finasteride in causing PD-related clinical features, an hypothesis which remains highly speculative due to the very questionable quality of present data., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Hormones and cytokines are known to regulate cellular functions in the testes. These biomolecules induce a broad spectrum of effects on various level of spermatogenesis, and among them is the modulation of cell junction restructuring between Sertoli cells and germ cells in the seminiferous epithelium. Cytokines and androgens are closely related, and both correct testicular development and the maintenance of spermatogenesis depend on their function. Cytokines also play a crucial role in the immune testicular system, activating and directing leucocytes across the endothelial barrier to the inflammatory site, as well as in increasing their adhesion to the vascular wall. The purpose of this review is to revise the most recent findings on molecular mechanisms that play a key role in male sexual function, focusing on three specific molecular patterns, namely, cytokines, miRNAs, and endothelial progenitor cells. Numerous reports on the interactions between the immune and endocrine systems can be found in the literature. However, there is not yet a multi-approach review of the literature underlying the role between molecular patterns and testicular and sexual function.

Background: To investigate the impact of COVID-19 outbreak on the diagnosis and treatment of non-muscle invasive bladder cancer (NMIBC)., Methods: A retrospective analysis was performed using an Italian multi-institutional database of TURBT patients with high-risk urothelial NMIBC between January 2019 and February 2021, followed by Re-TURBT and/or adjuvant intravesical BCG., Results: A total of 2591 patients from 27 institutions with primary TURBT were included. Of these, 1534 (59.2%) and 1056 (40.8%) underwent TURBT before and during the COVID-19 outbreak, respectively. Time between diagnosis and TURBT was significantly longer during the COVID-19 period (65 vs. 52 days, p = 0.002). One thousand and sixty-six patients (41.1%) received Re-TURBT, 604 (56.7%) during the pre-COVID-19. The median time to secondary resection was significantly longer during the COVID-19 period (55 vs. 48 days, p < 0.0001). A total of 977 patients underwent adjuvant intravesical therapy after primary or secondary resection, with a similar distribution across the two groups ( n = 453, 86% vs. n = 388, 86.2%). However, the proportion of the patients who underwent maintenance significantly differed (79.5% vs. 60.4%, p < 0.0001)., Conclusions: The COVID-19 pandemic represented an unprecedented challenge to our health system. Our study did not show significant differences in TURBT quality. However, a delay in treatment schedule and disease management was observed. Investigation of the oncological impacts of those differences should be advocated.

Previous studies have shown discrepancies among countries in terms of treatment indications and patients' management due to different health care policies. Penile prosthesis implantation (PPI) is a highly effective treatment for erectile dysfunction (ED), which may have different accessibility according to the type of health system. We compared clinical characteristics of patients included in two national registries on PPI to investigate the influence of different health care systems on treatment indication and accessibility. The multicenter Italian Nationwide Systematic Inventarization of Surgical Treatment for ED (INSIST-ED) Registry and the multicenter Prospective Registry of Outcomes with Penile Prosthesis for Erectile Restoration (PROPPER), respectively for Italy and North America were considered. Clinical characteristics of patients included in both registries were compared using Wilcoxon Rank Sum test and the Pearson's Chi square test. Patients submitted to PPI in Italy are significantly younger (age: 61.2 vs. 63.8 years; p ≤ 0.001) compared with North America. The majority of patients are treated for post-radical prostatectomy ED in both registries (Italy: 31%; North America: 27%), although diabetes and cardiovascular diseases are more frequent reasons for PPI in the PROPPER registry (p ≤ 0.001), reflecting differences in disease prevalence among countries. In North America a non-hydraulic implant is considered only in 1% of cases as compared with 3% in Italy (p ≤ 0.001). In terms of postoperative management, a compressive surgical dressing (98% vs. 24%; p ≤ 0.001) is a more common strategy in North America. Finally, in Italy most surgeries are performed in a public hospital (82%), while the private setting (70.8%) is more common in North America (p ≤ 0.001). These findings suggest differences in health care systems between Italy and North America. A system like the American one would guarantee easier access to PPI in countries where the National Health System is mainly based on reimbursement to public hospital settings and where patients choosing private settings have to pay by themselves., (© 2020. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To report safety and efficacy of interventional radiology procedures in the treatment of gynecologic iatrogenic urinary leaks., Methods: A retrospective analysis of iatrogenic ureteral lesions treated between November 2009 to April 2019 was performed. Under ultrasound (US) and fluoroscopy guidance, an attempt to place a ureteral stent and nephrostomy was carried out in the same session using an anterograde percutaneous approach. At the end of any procedure, a fluoroscopic control and a cone-beam CT scan (CBCT) were performed to check the correct placement and functioning of the nephrostomy and DJ stent. In cases of difficult ureteral stent placement via the single anterograde approach, the collaboration of urologists was requested to perform a rendezvous technique, combined with the retrograde approach., Results: DJ stent placement was achieved using the anterograde approach in 12/15 (80.0%) patients and using the retrograde approach in 3/15 cases (20.0%). Moreover, in 3/15 (20.0%) patients, surgical treatment was needed: in one case because of the persistence of ureteral stenosis at 6 months, and in the other two cases due to ureter-vaginal fistula. No major complications were recorded; overall, minor complications occurred in 4/8 patients., Conclusion: Percutaneous minimally invasive treatment of iatrogenic ureteral lesions after gynecological surgery is a safe and effective option.

Background: In the PURE-01 study (NCT02736266), we aimed to evaluate the ability to predict the pathologic complete response (pT0N0) after pembrolizumab by using clinical and tumor biomarkers., Methods: In an open-label, single-arm, phase 2 study, 3 courses of 200 mg pembrolizumab preceding radical cystectomy were administered in patients with T2-4aN0M0 muscle-invasive bladder cancer. The analyses included a comprehensive genomic profiling and programmed cell-death-ligand-1 (PD-L1)-combined positive score assessment (CPS; Dako 22C3 antibody) of pre- and posttherapy samples. Multivariable logistic regression analyses evaluated baseline clinical T stage and tumor biomarkers in association with pT0N0 response. Corresponding coefficients were used to develop a calculator of pT0N0 response based on the tumor mutational burden (TMB), CPS, and the clinical T stage. Decision-curve analysis was also performed. All statistical tests were 2-sided., Results: From February 2017 to June 2019, 112 patients with biomarker data were enrolled (105 with complete TMB and CPS data). Increasing TMB and CPS values featured a linear association with logistic pT0N0 probabilities (P = .02 and P = .004, respectively). For low TMB values (≤11 mut/Mb, median value, n = 53), pT0N0 probability was not associated with increasing CPS. Conversely, for high TMB values (>11 mut/Mb, n = 52), pT0N0 was statistically significantly associated with higher CPS (P = .004). The C index of the pT0N0 probability calculator was 0.77. On decision-curve analysis, the net benefit of the model was higher than the "treat-all" option within the clinically meaningful threshold probabilities of 40%-50%., Conclusions: The study presents a composite biomarker-based pT0N0 probability calculator that reveals the complex interplay between TMB and CPS, added to the clinical T stage., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To investigate scores and predictors of patient satisfaction at 1 year after penile prosthesis implantation (PPI) using the validated Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaire., Patients and Methods: Analyses were performed for 142 patients prospectively included in the national multicentre registry Italian Nationwide Systematic Inventarization of Surgical Treatment for Erectile Dysfunction (INSIST-ED), which provided 1-year follow-up data. Postoperative patient satisfaction was assessed using the validated QoLSPP tool. Linear logistic regression analyses assessed predictors of QoLSPP total and single domain scores, including age at surgery, erectile dysfunction aetiology, type of prosthesis, surgical approach, surgeon experience and complications. Locally weighted regression methods were used to explore the relationship between surgeon experience and QoLSPP scores., Results: Overall, high median functional, relational, social, personal and total QoLSPP scores were reported at 1 year after PPI. Patients implanted with hydraulic devices had higher functional (23 vs 21.5; P = 0.01) and total scores (68 vs 65.5; P = 0.03) than those with a malleable prosthesis. Surgeon experience emerged as the only independent predictor of higher satisfaction scores, depicting a non-linear association with both QoLSPP total and single domain scores (all P < 0.03). Data suggested that the higher the number of procedures per year, the greater the satisfaction scores, reaching a plateau after l5 procedures/year., Conclusions: This study reports high functional and patient satisfaction scores at 1 year after PPI surgery using a dedicated tool for the first time. Better outcomes should be expected for patients treated by surgeons with greater experience., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Background: The ability to identify clinically significant prostate cancer (csPCa) has dramatically improved with the introduction of multiparametric magnetic resonance imaging (mpMRI). Given the growing interest in targeted biopsy and focal therapy, improving our knowledge on the relationship between mpMRI parameters and the ability to predict csPCa multifocality is mandatory., Objective: To assess whether the Prostate Imaging Reporting and Data System (PI-RADS) score for the index lesion (IL) may predict multifocal csPCa undetected by mpMRI., Design, Setting, and Participants: The study included 343 patients who underwent mpMRI of the prostate with subsequent biopsy between 2014 and 2017 at a single tertiary care referral centre., Intervention: Lesions with a PI-RADS v.2 score ≥2 detected at mpMRI (IL) were targeted with a fusion biopsy (Bx) approach (mpMRI-Bx). Moreover, each patient underwent a random extended transrectal ultrasound-guided biopsy (TRUS-Bx) during the same session. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: csPCa outside the IL was defined as disease detected at TRUS-Bx with a Gleason score (GS)≥3+4 and equal to or greater than the GS for the IL. The extent of csPCa detected in target and random cores was reported and stratified according to the GS and PI-RADS score for the IL. The probability of diagnosing csPCa outside the IL according to the PI-RADS score was also assessed in multivariable logistic regression analyses (MVA) after accounting for confounders., Results and Limitations: The detection rate for csPCa outside the IL was 30%. The detection rate for csPCa at TRUS-Bx was 8% for PI-RADS 2, 15% for PI-RADS 3, 36% for PI-RADS 4, and 58% for PI-RADS 5 lesions (p=0.03). Overall, the median length of csPCa found at TRUS-Bx and thus missed at mpMRI was 2.6mm. However, the length significantly increased with PI-RADS score for the IL, and was 1.8, 2.3, 2.8, and 3.8mm for PI-RADS 2, 3, 4, and 5 lesions, respectively (p=0.03). On MVA, PI-RADS 4 (odds ratio [OR] 7.6; p=0.008) and PI-RADS 5 scores (OR 17.3; p<0.001) were independent predictors of the presence of csPCa outside the IL. The study is limited by its retrospective design., Conclusions: Overall, the accuracy of mpMRI in identifying multifocal csPCa is poor, missing low-volume csPCa in approximately 30% of patients. Moreover, the rate and the extent of csPCa undetected by mpMRI significantly increased with the PI-RADS score for the IL, which can thus be considered a proxy for tumour multifocality., Patient Summary: The accuracy of multiparametric magnetic resonance imaging in identifying prostate cancer multifocality is poor. False negative findings were highly related to the PI-RADS score of the index lesion. These findings raise concerns about the indication for targeting the index lesion only when considering prostate biopsy and focal approaches., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: In renal cell carcinoma (RCC), lymph node status at preoperative imaging is affected by a non-negligible false-positive rate. We aimed to investigate which factors are related to a concordance between clinical suspicion and pathological confirmation of lymph node invasion (LNI)., Methods: At a single tertiary care institution, 2954 RCC patients underwent either partial or radical nephrectomy. For the aim of the study, only clinically positive lymph node cases were included (cN1). Statistical analyses assessed the concordance between preoperative and pathological nodal status., Results: Preoperative axial CT scans revealed 424 (14.4 %) patients showing at least one enlarged lymph node suspected for LNI (cN1). All lymphadenopathies were removed at surgery, and LNI was pathologically confirmed (pN1) in 122 patients (28.8 %). When focusing the analyses on clinical characteristics (variables known before surgery), metastases at diagnosis [OR 3.0 (95 %1.9-4.8), p < 0.001] and tumor size [OR 1.1 (95 % 1.1-1.2), p < 0.001] were the two most informative predictors of concordance between clinical and pathological nodal status. Concordance was also more likely in patients with papillary type II tumors (55.6 %) relative to papillary type I (38.1 %), clear cell (27.7 %) and chromophobe (8.3 %) tumors. At multivariable analyses, none of the considered blood markers resulted to be independently associated with LNI., Conclusions: Roughly 70 % of patients showing a suspected lymph node preoperatively do not show LNI at the final pathological report. Among patients with clinically positive nodes, clinical tumor size and metastases at diagnosis represent the most informative and independent predictors of confirmed LNI at final pathology.