Spontaneous erectile function recovery among young men with erectile dysfunction taking tadalafil 5 mg once a day.

BACKGROUND: Daily (once a day [OaD]) tadalafil intake is a valuable option for men favoring spontaneous over scheduled sexual intercourse. AIM: The study sought to assess the rate of and the clinical factors associated with spontaneous, medication-free erectile function (EF) recovery after discontinuation of tadalafil 5 mg OaD in a cohort of young men seeking first medical help for psychogenic erectile dysfunction (ED) as their primary complaint. METHODS: Data from 96 consecutive patients <50 years of age seeking first medical help for ED and prescribed tadalafil 5 mg OaD were analyzed. Patients completed the International Index of Erectile Function (IIEF) and underwent baseline penile color Doppler ultrasound. Follow-up involved clinical assessments or phone interviews. Spontaneous medication-free EF recovery was defined as IIEF EF domain score >22 after tadalafil discontinuation, prompting cessation of follow-up. Descriptive statistics compared tadalafil OaD responders and nonresponders. Cox regression hazard models explored the association between baseline characteristics and EF recovery risk post-drug discontinuation. Kaplan-Meier analyses estimated EF recovery probability over time. OUTCOMES: The primary outcome was EF recovery after discontinuation of tadalafil 5 mg OaD. RESULTS: Overall, median age was 39 (interquartile range [IQR], 32-45) years. Of all, 82 (85.4%) patients achieved EF recovery after tadalafil OaD discontinuation, while 14 (14.6%) patients were identified as nonresponders. Median tadalafil usage time (from beginning to discontinuation) was 3 (IQR, 2-11) months. The most common treatment-emergent adverse event was headache in 9 (9.4%) patients. Nonresponders were older (43 [IQR, 42-45] years vs 38 [IQR, 31-44] years; P = .03), had higher body mass index (25.5 [IQR, 23.4-29.9] kg/m2 vs 23.6 [IQR, 21.8-25.9] kg/m2; P = .04), and reported lower baseline IIEF EF domain scores (12 [IQR, 7-15] vs 15 [IQR, 10-22]; P = .02) than responders. Nonresponders and responders did not differ in terms of baseline ED severity, Charlson comorbidity index, smoking, alcohol consumption, regular physical exercise, and color Doppler ultrasound parameters. Upon Cox regression analysis, younger age (hazard ratio, 0.95; 95% confidence interval, 0.92-0.99; P = .01) was associated to EF recovery, after adjusting for baseline ED severity, body mass index, smoking, and Charlson comorbidity index ≥1. The Kaplan-Meier analysis displays the probability of EF recovery over time, indicating rates of 43%, 60%, and 72% at 3-, 6-, and 12-month follow-up intervals, respectively. CLINICAL IMPLICATIONS: Tadalafil 5 mg OaD is an effective short-term treatment for psychogenic ED, allowing its discontinuation after achieving a normal medication-free EF. STRENGTHS AND LIMITATIONS: The main limitations are the limited number of participants and the potential neglect of confounding factors. CONCLUSION: Almost 1 out of 2 young men with primary psychogenic ED who were prescribed with tadalafil 5 mg OaD recovered spontaneous medication-free EF after 3 months of treatment. Overall, the younger the patient was, the higher the chance there was of spontaneous EF recovery after drug discontinuation.

Conservative treatment of Peyronie's disease: a guide.

PURPOSE: To review the literature on the topic, to suggest a common line of treatment applicable across a wide community of specialists, and to contribute in maintaining the high level of interest in this disease. METHODS: A comprehensive and exhaustive review of the literature was performed, identifying hundreds of articles on the topic. RESULTS: Peyronie's disease is a condition that has been recognized, studied, and treated for centuries; despite this, if one excludes surgery in cases in which the deformity is stable, no clear treatment (or line of treatment) is available for complete relief of signs and symptoms. Treatment options were divided into local, oral, and injection therapy, and a wide variety of drugs, remedies, and options were identified. CONCLUSIONS: Low-intensity extracorporeal shock wave therapy, vacuum therapy, penile traction therapy, phosphodiesterase type 5 inhibitors, hyaluronic acid, and collagenase of Clostridium histolyticum may be recommended only in specific contexts. Further studies on individual options or potential combinations are required.

Vacuum-assisted mini-percutaneous nephrolithotomy is associated with lower rates of infectious complications compared to vacuum-cleaner procedure in patients at high risk for infections: a single-center experience.

PURPOSE: To evaluate the impact of vacuum-assisted mini-percutaneous nephrolithotomy (vamPCNL) vs. vacuum-cleaner mPCNL (vcmPCNL) on the rate of postoperative infectious complications in a cohort of patients with high risk factors for infections. METHODS: We retrospectively analysed data from 145 patients who underwent mPCNL between 01/2016 and 12/2022. Patient's demographics, stones characteristics and operative data were collected. vamPCNL and vcmPCNL were performed based on the surgeon's preference. High-risk patients were defied as having ≥ 2 predisposing factors for infections such as a history of previous urinary tract infections, positive urine culture before surgery, stone diameter ≥ 3 cm, diabetes mellitus and hydronephrosis. Complications were graded according to modified Clavien classification. Descriptive statistics and logistic regression models were used to identify factors associated with postoperative infectious complications. RESULTS: vamPCNL and vcmPCNL were performed in 94 (64.8%) and 51 (35.2%) cases, respectively. After surgery, infectious complications occurred in 43 (29.7%) participants. Patients who developed infectious complications had larger stone volume (p = 0.02) and higher rate of multiple stones (p = 0.01) than those who did not. Infectious complications occurred more frequently after vcmPCNL than vamPCNL (55.9% vs. 44.1%. p = 0.01) in high-risk patients. Longer operative time (p < 0.01) and length of stay (p < 0.01) were observed in cases with infectious complications. At multivariable logistic regression analysis, longer operative time (OR 1.1, p = 0.02) and vcmPCNL (OR 3.1, p = 0.03) procedures were independently associated with the risk of infectious complications post mPCNL, after accounting for stone volume. CONCLUSION: One out of three high-risk patients showed infectious complications after mPCNL. vamPCL and shorter operative time were independent protective factors for infections after surgery.

Extended pelvic lymph node dissection during robotic prostatectomy: antegrade versus retrograde technique.

BACKGROUND: Robot-assisted radical prostatectomy (RARP) with extended lymphadenectomy (ePLND) is the gold standard for surgical treatment of prostate cancer (PCa). Recently, the en-bloc ePLND has been proposed but no studies reported on the standardization of the technique. The aim of the study is to describe different standardized en-bloc ePLND, the antegrade and the retrograde ePLND, and to compare their surgical and oncological outcomes. MATERIALS & METHODS: From January 2018 to September 2019, all patients subjected to RARP plus ePLND by one single surgeon were enrolled. ePLND was performed in a retrograde fashion by starting laterally to the medial umbilical ligament from the internal inguinal ring proceeding towards the ureter, or in an antegrade way by starting from the ureter at its crossing with the common iliac artery and proceeding towards the femoral canal. Patients' demographic data, clinical and surgical data were collected. Each en-bloc ePLND was categorized as "efficient" or "inefficient" by the operator, as surrogate of surgeon's satisfaction. RESULTS: Antegrade and retrograde ePLND were performed in 41/105 (group A) and 64/105 (group R) patients, respectively. The two groups (A vs R) had similar median (IQR) number of lymph nodes retrieved [20 (16.25-31.5) vs 19 (15-26.25); p = 0.18], ePLND time [33.5 (29.5-38.5) min vs 33.5 (26.5-37.5) min; p = 0.4] and post-operative complications [8/41 (19.5%) vs 9/64 (14.1%); p = 0.61]. In group A, 3/41 (7.3%) clinically significant lymphoceles were reported, while 1/64 (1.6%) in group R (p = 0.3). 33/41 (80.5%) and 28/64 (44%) procedures were scored as efficient 59 in group A and R, respectively (p = 0.01). On multivariate regression, only BMI (B = 0.93; 95% CI 0.29-1.56; p = 0.005) was associated with a longer ePLND time. CONCLUSIONS: The study indicates that antegrade and retrograde en-bloc extended pelvic lymph node dissection (ePLND) have comparable surgical and oncologic outcomes, supporting the importance of standardizing the procedure rather than focusing on the direction. Although both techniques aligned with current evidence regarding lymph node invasion and complications, the antegrade approach was subjectively perceived as safer due to early isolation of critical anatomical landmarks. Encouragement for the use of en-bloc ePLND, regardless of direction, is emphasized to improve prostate cancer staging accuracy and procedural standardization.

Perioperative and Survival Outcomes of Patients Treated With Robot-Assisted Partial Nephrectomy and Percutaneous Microwave Ablation for Small Renal Masses: A Single Center Experience.

BACKGROUND: Robot assisted partial nephrectomy (RAPN) and microwave ablation (MWA) are 2 of the most advanced techniques for the management of localized small renal masses. PURPOSE: To compare the perioperative, functional and oncological results of RAPN and MWA. MATERIALS AND METHODS: Data from 171 consecutive patients undergoing either RAPN or MWA for a localized small renal mass at a single academic center was retrospectively collected. Baseline features included patients' demographics and masses' characteristics. Procedures were compared in terms of perioperative outcomes and renal function variation Progression of a persistent lesion or local recurrence after a complete treatment defined local tumor progression. Descriptive statistics and survival analysis tested the association between predictors and local tumor progression. RESULTS: Of all, 109 and 62 patients underwent RAPN and MWA. Patients in the MWA group were older (P = .002) had higher Charlson Comorbidity Index (CCI) (P < .001) and higher frequency of preoperative chronic kidney disease (P < .001). MWA led to a shorter postoperative hospitalization time (P < .001) and lower incidence of medical complications (6.5% vs. 22.9%, P = .02) than RAPN. GFR decline was similar between groups both at discharge (P = .39) and at the time of last follow up (P = 1.00). A lower rate of secondary interventions (11.7% vs. 2.8%, P = .037) and a better disease-free survival (83.2% vs. 96.5%, P = .027) were reported after RAPN. Conversely, cancer specific and overall survival were comparable (P > .05). At univariate regression analysis, MWA was associated with local tumor progression (HR 3.46, P = .040). CONCLUSION: MWA displayed a lower perioperative impact, while functional outcomes were similar after each intervention. RAPN resulted superior in terms of tumor eradication, but no difference was noted regarding cancer specific survival. Thus, MWA represents a valid alternative in frail patients, though less radical than RAPN.

A Systematic Review and Meta-analysis on the Impact of Infertility on Men's General Health.

CONTEXT: Male infertility has been associated with increased morbidity and mortality. OBJECTIVE: To perform a systematic review and meta-analysis to provide the most critical evidence on the association between infertility and the risk of incident comorbidities in males. EVIDENCE ACQUISITION: A systematic review and meta-analysis was performed according to the Meta-analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and registered on PROSPERO. All published studies on infertile versus fertile men regarding overall mortality and risks of cancer, diabetes, and cardiovascular events were selected from a database search on PubMed, EMBASE, Google Scholar, and Cochrane. Forest plot and quasi-individual patient data meta-analysis were used for pooled analyses. A risk of bias was assessed using the ROBINS-E tool. EVIDENCE SYNTHESIS: Overall, an increased risk of death from any cause was found for infertile men (hazard risk [HR] 1.37, [95% confidence interval {CI} 1.04-1.81], p = 0.027), and a 30-yr survival probability of 91.0% (95% CI 89.6-92.4%) was found for infertile versus 95.9% (95% CI 95.3-96.4%) for fertile men (p < 0.001). An increased risk emerged of being diagnosed with testis cancer (relative risk [RR] 1.86 [95% CI 1.41-2.45], p < 0.001), melanoma (RR 1.30 [95% CI 1.08-1.56], p = 0.006), and prostate cancer (RR 1.66 [95% CI 1.06-2.61], p < 0.001). As well, an increased risk of diabetes (HR 1.39 [95% CI 1.09-1.71], p = 0.008), with a 30-yr probability of diabetes of 25.0% (95% CI 21.1-26.9%) for infertile versus 17.1% (95% CI 16.1-18.1%) for fertile men (p < 0.001), and an increased risk of cardiovascular events (HR 1.20 [95% CI 1.00-1.44], p = 0.049), with a probability of major cardiovascular events of 13.9% (95% CI 13.3-14.6%) for fertile versus 15.7% (95% CI 14.3-16.9%) for infertile men (p = 0.008), emerged. CONCLUSIONS: There is statistical evidence that a diagnosis of male infertility is associated with increased risks of death and incident comorbidities. Owing to the overall high risk of bias, results should be interpreted carefully. PATIENT SUMMARY: Male fertility is a proxy of general men's health and as such should be seen as an opportunity to improve preventive strategies for overall men's health beyond the immediate reproductive goals.

Advanced Age Impacts Survival After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.

INTRODUCTION: Upper tract urothelial carcinoma is rare but has a poor prognosis. Prognostic factors have been extensively studied in order to provide the best possible management for patients. We have aimed to investigate commonly available factors predictive of recurrence and survival in this patient population at high risk of death and recurrence, with an emphasis on the effects of age (using a cutoff of 70 years) on survival outcomes. PATIENTS AND METHODS: From 1387 patients with clinically nonmetastatic upper tract urothelial carcinoma treated with radical nephroureterectomy at 21 academic hospital centers between 2005 and 2021, 776 patients were eligible and included in the study. Univariable and multivariable Cox regression models were built to evaluate the independent prognosticators for intravesical and extravesical recurrence, overall survival, and cancer-specific survival according to age groups. A P value of <.05 was considered statistically significant. RESULTS: We did not find an association between groups aged <70 and >70 years old and preoperatively clinical or histopathological characteristics. Kaplan-Meier analysis was found no statistical significance between the 2 age groups in terms of intravesical or extravesical recurrence (P = .09 and P = .57). Overall survival (P = .0001) and cancer-specific survival (P = .0001) have been found to be statistically significantly associated with age as independent predictors (confounding factors: gender, tumor size, tumor side, clinical T stage, localization, preoperative hydronephrosis, tumor localization, type of surgery, multifocality of the tumor, pathological grade, lymphovascular invasion, concomitant CIS, lymph node status, necrosis, or history of previous bladder cancer). CONCLUSION: This research confirms that patients aged 70 and above who undergo radical nephroureterectomy may have worse outcomes compared to younger patients, older patients needing an improved care and management of UTUC to improve their outcomes in the setting of an increase in this aged population group.

Hyperestrogenism is associated with sexual function impairment in men-findings from a cross-sectional, real-life study.

BACKGROUND: Hyperestrogenism is believed to be harmful to male sexuality. We aimed to investigate the prevalence of and the impact of hyperestrogenism on sexual functioning in a cohort of men seeking medical attention for new-onset erectile dysfunction. MATERIALS AND METHODS: Data from 547 men seeking first medical help for new-onset erectile dysfunction at a single andrology center were analyzed. Patients were assessed with a thorough medical and sexual history. Comorbidities were scored with the Charlson comorbidity index. All patients completed the International index of erectile function; the International index of erectile function-erectile function domain was categorized according to Cappelleri's criteria. Circulating hormones were measured in every patient. Hyperestrogenism was defined as estradiol levels >42.6 pg/mL (Tan et al., 2015). Descriptive statistics and logistic/linear regression models tested the association between hyperestrogenism and International index of erectile function domains score. RESULTS: Overall, 96 (17.6%) participants had serum estrogen levels suggestive of hyperestrogenism. Men with hyperestrogenism were older (median [interquartile range]: 46 [35-59] vs. 44 [31-56] years; p < 0.001), had a higher rate of comorbidities (Charlson comorbidity index ≥1: 26.0% vs. 7.4%; p < 0.001), and higher serum total testosterone values (5.4 [5.2-8.0] vs. 4.3 [4.1-5.7] ng/mL; p = 0.01) than those with normal estradiol values. A higher prevalence of severe erectile dysfunction (135 [29.9%] vs. 47 [48.9%] men; p = 0.01) and of hypogonadism (22 [4.8%] vs. 6 [6.3%] men; p = 0.004) were found in men with hyperestrogenism. Serum estradiol levels were positively correlated with total testosterone levels (ß = 0.26, p < 0.001) but negatively correlated with International index of erectile function-orgasmic function (ß = -0.24, p = 0.002) and International index of erectile function-erectile function scores (ß = -0.03, p < 0.001). When International index of erectile function scores was used to stratify erectile dysfunction patients, hyperestrogenism (odds ratio 2.44, p = 0.02) was associated with severe erectile dysfunction. CONCLUSIONS: One out of five men seeking first medical help for erectile dysfunction showed elevated serum estradiol values suggestive of hyperestrogenism. Hyperestrogenism was associated with health-significant comorbidities, orgasmic function impairment, and erectile dysfunction severity.

Diagnosis of prostate cancer with magnetic resonance imaging in men treated with 5-alpha-reductase inhibitors.

PURPOSE: The primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer (csPCa) (ISUP Gleason grade ≥ 2). METHODS: This study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of MRI were compared in treated and untreated patients. RESULTS: 705 patients (9%) were treated with 5-ARIs [median age 69 years, Interquartile range (IQR): 65, 73; median PSA 6.3 ng/ml, IQR 4.0, 9.0; median prostate volume 53 ml, IQR 40, 72] and 6913 were 5-ARIs naïve (age 66 years, IQR 60, 71; PSA 6.5 ng/ml, IQR 4.8, 9.0; prostate volume 50 ml, IQR 37, 65). MRI showed PIRADS 1-2, 3, 4, and 5 lesions in 141 (20%), 158 (22%), 258 (37%), and 148 (21%) patients treated with 5-ARIs, and 878 (13%), 1764 (25%), 2948 (43%), and 1323 (19%) of untreated patients (p < 0.0001). No difference was found in csPCa detection rates, but diagnosis of high-grade PCa (ISUP GG ≥ 3) was higher in treated patients (23% vs 19%, p = 0.013). We did not find any evidence of interaction between PIRADS score and 5-ARIs exposure in predicting csPCa. Sensitivity, specificity, PPV, and NPV of PIRADS ≥ 3 were 94%, 29%, 46%, and 88% in treated patients and 96%, 18%, 43%, and 88% in untreated patients, respectively. CONCLUSIONS: Exposure to 5-ARIs does not affect the association of PIRADS score with csPCa. Higher rates of high-grade PCa were detected in treated patients, but most were clearly visible on MRI as PIRADS 4 and 5 lesions. TRIAL REGISTRATION: The present study was registered at ClinicalTrials.gov number: NCT05078359.

Clinical and time-related predictors of sepsis in patients with obstructive uropathy due to ureteral stones in the emergency setting.

PURPOSE: Well-defined clinical predictors of sepsis after upper tract drainage for obstructive uropathy due to ureteral stones are needed. We aim to determine whether sepsis after decompression of the upper urinary tract may be predicted by clinical and time-related factors, specifically delay time from symptom onset to hospital presentation (StH) and from hospital presentation to surgical decompression (HtD). METHODS: In this single-center retrospective study, data from 196 consecutive patients presenting to the emergency department for obstructive uropathy due to ureteral stones and submitted to surgical decompression were evaluated. Postoperative sepsis was defined as an acute increase in ≥ 2 SOFA points and documented blood or urine cultures. RESULTS: Median StH and HtD were 24 (6-48) and 17 (10-30) hours, respectively. Thirty-three (16.8%) patients developed sepsis. Septic patients were more frequently female (75.8% vs. 37.4%, p < 0.001), had higher preoperative max body temperature (p < 0.001), white blood cells (WBC) count (p < 0.01), C-reactive protein (CRP) values (p < 0.001) and larger stone diameter (7.2 vs. 6 mm, p = 0.02). StH and HtD did not differ according to sepsis status. Time for WBC normalization and CRP halving were longer for septic patients (all p < 0.02). At multivariable logistic regression analysis, max body temperature ≥ 38 °C (OR 21.5; p < 0.001), female gender (OR 3.6; p = 0.02) and higher CRP (OR 1.1; p < 0.001) were independently associated with sepsis status. CONCLUSION: Clinical and laboratory parameters are associated with an increased risk of sepsis after decompression. StH and HtD timing are not associated with higher sepsis rates. In selected patients, urinary decompression could be delayed or primary ureteroscopy could be considered.

Anti-Müllerian hormone predicts positive sperm retrieval in men with idiopathic non-obstructive azoospermia-findings from a multi-centric cross-sectional study.

STUDY QUESTION: Is it possible to identify a reliable marker of successful sperm retrieval (+SR) in men with idiopathic non-obstructive azoospermia (iNOA) undergoing microdissection testicular sperm extraction (mTESE)? SUMMARY ANSWER: A higher likelihood of +SR during mTESE is observed in men with iNOA and lower preoperative serum anti-Müllerian hormone (AMH) levels, with good predictive accuracy achieved using an AMH threshold of <4 ng/ml. WHAT IS KNOWN ALREADY: AMH has been previously linked to +SR in men with iNOA undergoing mTESE prior to ART. STUDY DESIGN, SIZE, DURATION: A multi-centre cross-sectional study was carried out with a cohort of 117 men with iNOA undergoing mTESE at three tertiary-referral centres. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from 117 consecutive white-European men with iNOA presenting for primary couple's infertility associated with a pure male factor at three centres were analysed. Descriptive statistics was applied to compare patients with negative (-SR) versus +SR at mTESE. Multivariate logistic regression models were fitted to predict +SR at mTESE, after adjusting for possible confounders. Diagnostic accuracy of the factors associated with +SR was assessed. Decision curve analyses were used to display the clinical benefit. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 60 (51.3%) men had an -SR and 57 (48.7%) had a +SR at mTESE. Patients with +SR had lower levels of baseline AMH (P = 0.005) and higher levels of estradiol (E2) (P = 0.01). At multivariate logistic regression analysis, lower levels of AMH (odds ratio: 0.79; 95% CI: 0.64-0.93, P = 0.03) were associated with +SR at mTESE, after adjusting for possible confounders (e.g. age, mean testicular volume, FSH, and E2). A threshold of AMH <4 ng/ml achieved the highest accuracy for +SR at mTESE, with an AUC of 70.3% (95% CI: 59.8-80.7). Decision curve analysis displayed the net clinical benefit of using an AMH <4 ng/ml threshold. LIMITATIONS, REASONS FOR CAUTION: There is a need for external validation in even larger cohorts, across different centres and ethnicities. Systematic reviews and meta-analysis to provide high level of evidence are lacking in the context of AMH and SR rates in men with iNOA. WIDER IMPLICATIONS OF THE FINDINGS: Current findings suggest that slightly more than one in two men with iNOA had -SR at mTESE. Overall, men with iNOA with lower levels of AMH had a significantly higher percentage of successful SR at surgery. A threshold of <4 ng/ml for circulating AMH ensured satisfactory sensitivity, specificity, and positive predictive values in the context of +SR at mTESE. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by voluntary donations from the Urological Research Institute (URI). All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Kidney function impairment in men with primary infertility: A case-control analysis.

BACKGROUND: Infertile men have a worse overall health status than their fertile counterparts. OBJECTIVE: We aimed to (1) compare kidney function in men presenting for primary couple's infertility with that of fertile men and (2) assess kidney function impairment toward sperm quality in infertile men. MATERIALS AND METHODS: In this case-control study, 387 consecutive white-European infertile men were matched by age with 134 same-ethnicity fertile men. Complete clinical and laboratory data were available for each patient. The Chronic Kidney Disease Epidemiology Collaboration function was used for estimated glomerular filtration rate calculation. Kidney functional impairment was defined as an estimated glomerular filtration rate <90 mL/min per 1.73 m2 , according to the Kidney Disease Improving Global Outcomes criteria. Multivariable logistic regression analysis was used to (1) assess the association between kidney function impairment and infertility status and (2) investigate the association between kidney function and semen analysis abnormalities in infertile men. RESULTS: After matching, 34 (8.8%) infertile men depicted at least a mild unknown impairment of kidney function compared to only four (3%) fertile men, with four (3%) of the infertile presenting with an overt kidney function impairment (estimated glomerular filtration rate <60 mL/min per 1.73 m2 ). There were no differences in terms of age, body mass index and rate of comorbidities between the two groups (all p > 0.05). After adjusting for major confounders, infertility status was associated with a higher risk of reduced estimated glomerular filtration rate (odds ratio 3.20; 95% confidence interval 1.21-5.2; p = 0.002). Conversely, estimated glomerular filtration rate was not associated with sperm abnormalities in infertile men. CONCLUSIONS: Mild kidney function impairment was found in 9% of asymptomatic and unaware men presenting for primary couple's infertility investigation. This novel finding corroborates growing data on a significant association of male infertility with a poorer overall male health status and the need for tailored preventive strategies.

Radiation Exposure and Surgical Outcomes after Antegrade Sclerotherapy for the Treatment of Varicocele in the Paediatric Population: A Single Centre Experience.

INTRODUCTION: Antegrade sclerotherapy (Tauber) effectively treats varicocele. However, fluoroscopy exposes young males to ionizing radiation. We aimed to evaluate radiation exposure and surgical outcomes after the Tauber procedure. MATERIALS AND METHODS: We retrospectively analysed data from 251 patients. Dose area product (DAP) and fluoroscopy time were recorded. The effective dose was calculated with the PCXMC software. Descriptive statistics and linear regression tested the association between clinical predictors and radiation exposure. RESULTS: Median (IQR) age and body mass index (BMI) were 14 (13-16) years and 20.1 (17.9-21.6) kg/m². Five (2.1%) patients developed clinical recurrence and two (0.81%) developed complications. Median fluoroscopy time and DAP were 38.5 (27.7-54.0) s and 89.6 (62.5-143.9) cGy*cm2. The effective dose was 0.19 (0.14-0.31) mSv. Fluoroscopy time was higher in patients with collateral veins (41 (26-49) s vs. 36 (31-61) s, p = 0.02). The median amount of sclerosing agent (SA) used was 3 (3-4) ml. DAP was higher when SA > 3 mL was used (101.4 (65-183) cGy*cm2 vs. 80.5 (59-119) cGy*cm2; p < 0.01). At univariable linear regression, age, BMI, operative time and SA > 3 mL were associated with higher DAP (all p < 0.01). At multivariable linear regression, only BMI (beta 12.9, p < 0.001) and operative time (beta 1.9, p < 0.01) emerged as predictors of higher DAP, after accounting for age and SA > 3 mL. CONCLUSIONS: The Tauber procedure is safe and associated with low effective doses. Operative time and the patient's BMI independently predict a higher radiation dose.

The symptomatic burden of Peyronie's disease at presentation according to patient age: A critical analysis of the Peyronie's disease questionnaire (PDQ) domains.

BACKGROUND: Peyronie's disease (PD) has a huge impact on patients' physical and psychological wellbeing. OBJECTIVES: To investigate whether patients' age has an impact on PD symptomatic burden at first presentation. MATERIALS AND METHODS: Data from 129 consecutive heterosexual patients seeking first medical attention for PD at a single andrological tertiary-referral centre were collected. All patients completed the International Index for Erectile Function (IIEF) and the PD questionnaire (PDQ). Descriptive statistics were used to compare clinical features between younger (≤40years) and older (>40 years) patients. Multivariable linear model assessed the impact of age, the degree of penile curvature and their impact on PDQ (total scores and its domains), after adjusting for PD duration and IIEF-erectile function domain scores. RESULTS: Of 129, 24 (18.6%) patients were ≤40 years old. Young patients presented with a less severe curvature than older patients (median [interquartile ranges] 20° [15-36] vs. 50° [40-80]; p = 0.04). However, younger age was associated with higher psychological and physical symptoms, PDQ-penile pain and PDQ-symptom bother scores (Coeff -0.11, -0.21 and -0.17, respectively) (all p < 0.05). Moreover, the greater the degree of curvature, the higher the PDQ-psychological and physical symptoms and the PDQ-symptom bother scores (Coeff. 0.21 and 0.22, respectively; all p < 0.05). CONCLUSION: Around one in five men seeking first medical help for PD is younger than 40 years at presentation in the real-life setting. PD-related distress varies according to patients' age, with younger men presenting with a greater risk of penile pain and symptom bother despite lower curvature.

The clinical role of bacteremia and bacterial spread into the irrigation fluid during percutaneous nephrolithotomy: a prospective study.

PURPOSE: Backflow of pathogens and endotoxins from the renal pelvis to the bloodstream is one supposed mechanism for infectious complications development after endourological stones surgery. The aim of this study is detecting to prove bacterial spread into irrigation fluid and bloodstream during percutaneous nephrolithotomy (PCNL) and to correlate these findings with clinical and microbiological parameters and infectious complications (IC). METHODS: Bladder urine culture (BUC) was retrieved before PCNL; during the procedure, 2 blood samples (BC) and an irrigation fluid sample during fragmentation (SFUC) were collected for culture. Stone culture (SC) was also obtained. Patients were evaluated post-operatively for IC. RESULTS: Sixty-one patients were prospectively included. IC occurred in 15 patients (24.6%). SFUC was positive in 7/61 (11.5%); BC in 10/61 (16.4%). Among patients with positive BC; BUC, SFUC and SC were positive in 9 (90%), 6 (60%), and 8 (80%) cases, respectively. Out of 10 patients with positive BC, 4 developed post-operative IC. Pre-operative renal impairment (p = 0.04), intraoperative-evaluated stone residual (p = 0.02), BUC (p = 0.004), and SC (p = 0.008) were associated with IC. No correlation was found between bacterial spread in the irrigation fluid and blood and IC. CONCLUSION: We proved that bacteria can be detected into the irrigation fluid and blood during PCNL. This transient bacteremia appears to be unrelated to IC development.

High serum alpha-fetoprotein levels in primary infertile men.

BACKGROUND: Alfa-fetoprotein (AFP) is a serum glycoprotein highly produced during fetal development. While AFP synthesis drops dramatically after birth, AFP production only persists or returns under specific pathological condition. OBJECTIVE: We sought to investigate the rate of and the potential meaning of high AFP serum levels in men seeking first medical attention for couple's primary infertility. MATERIALS AND METHODS: Socio-demographic and clinical data from 1803 non-Finnish, White-European primary infertile men were retrospectively analysed. AFP was routinely measured in each patient (high AFP was defined as >7 ng/ml). Men with history of liver diseases, testicular cancer, or other known causes of increased AFP levels were excluded from the final analysis. Semen analyses were based on the 2010 World Health Organization reference criteria. Descriptive statistics and logistic regression models tested the association between serum AFP and clinical variables. Possible nonlinear relationships were graphically explored with locally estimated scatterplot smoothing method. RESULTS: Overall, high serum AFP level was found in 29 (1.7%) patients. Normal versus high AFP levels patients were comparable in terms of body mass index (BMI), Charlson Comorbidity Index, waist circumference, smoking habits, history of cryptorchidism, testicular volume, and serum hormones (i.e., follicle-stimulating hormone, luteinizing hormone, and total testosterone). Conversely, men with higher AFP levels were older (p = 0.02), had lower sperm concentration (p = 0.003), and were more frequently oligozoospermic and azoospermic (all p ≤ 0.03). At multivariate analysis, high AFP levels were independently associated with oligozoospermia (OR 3.79; p = 0.033) and azoospermia (OR 3.29; p = 0.006). Likewise, if AFP levels increase, patients were found to be older, with higher BMI and to have more comorbidities (all p < 0.05). DISCUSSION: Unexplained high AFP levels account for almost 2% of cases in primary infertile patients without a previous history of associated disorders. Higher serum AFP levels are linked with aberrant sperm counts, older age, obesity, and a greater amount of comorbid conditions. CONCLUSION: Despite the need for additional validation, these data suggest that serum AFP measurement might have a multifaceted role over the diagnostic work-up of males presenting for couple's infertility.

Haemospermia in the Real- Life Setting: A New High-Risk Stratification.

OBJECTIVE: To (i) identify a novel risk stratification for patients complaining of haemospermia; and, (ii) compare its predictive ability to select high-risk patients by retrospectively validating the EAU guidelines classification. METHODS: Data from 283 consecutive patients complaining of a single episode/recurrent haemospermia were retrospectively analyzed. Patients were stratified into low vs high-risk according to EAU guidelines, whose diagnostic performance was then validated. We identified a new risk stratification model based on clinical factors associated with (i) positive semen culture and (ii) prostate cancer (PCa) and bladder cancer (BC). Diagnostic accuracy of the two predictive models (EAU vs New) was assessed and decision curve analyses (DCA) tested their clinical benefit. RESULTS: Overall, 259 (91.5%) were high-risk and 24 (8.5%) low risk according to the EAU guidelines. Recurrent haemospermia was reported by 134 (47.4%) patients. 126 (44.5%) had baseline CCI score ≥ 1. At MVA logistic regression analysis, history of recurrent genito - urinary tract infections was identified as a predictor for positive semen culture (OR: 3.39, 95% CI: 1.77 - 6.57, P =.002). Likewise, baseline CCI ≥ 1 was identified as a predictor for PCa and BC (OR: 1.55, 95% CI: 1.17 - 2.04, P =.009). Sensitivity, specificity, and AUC of the EAU guidelines were 13.3%, 89.2% and 51% respectively, whereas the new model performed substantially better: 98.9%, 58% and 78% respectively. CONCLUSION: The application of the EAU guidelines risk stratification does not ensure proper identification of high-risk patients complaining of haemospermia. We propose a novel, better performing and easily implementable risk stratification tool.

Combined plasma levels of IL-10 and testosterone, but not soluble HLA-G5, predict the risk of death in COVID-19 patients.

BACKGROUND: The identification of biomarkers correlated with coronavirus disease 2019 (COVID-19) outcomes is a relevant need for clinical management. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by elevated interleukin (IL)-6, IL-10, HLA-G, and impaired testosterone production. OBJECTIVES: We aimed at defining the combined impact of sex hormones, interleukin-10, and HLA-G on COVID-19 pathophysiology and their relationship in male patients. MATERIALS AND METHODS: We measured by chemiluminescence immunoassay, electrochemiluminescent assays, and enzyme-linked immunosorbent assay circulating total testosterone, 17ß-estradiol (E2 ), IL-10, and -HLAG5 as well as SARS-CoV-2 S1/S2 Immunoglobulin G from 292 healthy controls and 111 COVID-19 patients with different disease severity at hospital admission, and in 53 COVID-19 patients at 7-month follow-up. RESULTS AND DISCUSSION: We found significantly higher levels of IL-10, HLA-G, and E2 in COVID-19 patients compared to healthy controls and an inverse correlation between IL-10 and testosterone, with IL-10, progressively increasing and testosterone progressively decreasing with disease severity. This correlation was lost at the 7-month follow-up. The risk of death in COVID-19 patients with low testosterone increased in the presence of high IL-10. A negative correlation between SARS-CoV-2 Immunoglobulin G and HLA-G or IL-10 at hospitalization was observed. At the 7-month follow-up, IL-10 and testosterone normalized, and  HLA-G decreased. CONCLUSION: Our findings indicate that combined evaluation of IL-10 and testosterone predicts the risk of death in men with COVID-19 and support the hypothesis that IL-10 fails to suppress excessive inflammation by promoting viral spreading.

Radiological features characterising indeterminate testes masses: a systematic review and meta-analysis.

CONTEXT: The use of scrotal ultrasonography (SUS) has increased the detection rate of indeterminate testicular masses. Defining radiological characteristics that identify malignancy may reduce the number of men undergoing unnecessary radical orchidectomy. OBJECTIVE: To define which SUS or scrotal magnetic resonance imaging (MRI) characteristics can predict benign or malignant disease in pre- or post-pubertal males with indeterminate testicular masses. EVIDENCE ACQUISITION: This systematic review was conducted in accordance with Cochrane Collaboration guidance. Medline, Embase, Cochrane controlled trials and systematic reviews databases were searched from (1970 to 26 March 2021). Benign and malignant masses were classified using the reported reference test: i.e., histopathology, or 12 months progression-free radiological surveillance. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2). EVIDENCE SYNTHESIS: A total of 32 studies were identified, including 1692 masses of which 28 studies and 1550 masses reported SUS features, four studies and 142 masses reported MRI features. Meta-analysis of different SUS (B-mode) values in post-pubertal men demonstrated that a size of ≤0.5 cm had a significantly lower odds ratio (OR) of malignancy compared to masses of >0.5 cm (P < 0.001). Comparison of masses of 0.6-1.0 cm and masses of >1.5 cm also demonstrated a significantly lower OR of malignancy (P = 0.04). There was no significant difference between masses of 0.6-1.0 and 1.1-1.5 cm. SUS in post-pubertal men also had a statistically significantly lower OR of malignancy for heterogenous masses vs homogenous masses (P = 0.04), hyperechogenic vs hypoechogenic masses (P < 0.01), normal vs increased enhancement (P < 0.01), and peripheral vs central vascularity (P < 0.01), respectively. There were limited data on pre-pubertal SUS, pre-pubertal MRI and post-pubertal MRI. CONCLUSIONS: This meta-analysis identifies radiological characteristics that have a lower OR of malignancy and may be of value in the management of the indeterminate testis mass.

Are finasteride-related penile curvature/Peyronie's disease Adverse Event Reports worthy of further clinical investigation? Disproportionality analysis based on both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) pharmacovigilance databases.

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.