One out of two idiopathic infertile men has pathologic sperm DNA fragmentation values: Potential implications for clinical practice.

OBJECTIVES: To investigate the distribution of sperm DNA fragmentation (SDF) values and their association with clinical and seminal parameters in idiopathic infertile men. DESIGN, PATIENTS, MEASUREMENTS: Data from 3224 primary infertile men (belonging to couples having failed to conceive a pregnancy within 12 months) who underwent a thorough diagnostic work-up were analysed. A SDF value ≥ 30% (according to Sperm Chromatin Structure Assay) was considered pathologic. We excluded: (1) men with genetic abnormalities; (2) men with history of cryptorchidism; (3) men with biochemical hypogonadism; (4) men with clinical varicocele; and (5) men with other possible known aetiological factors. Descriptive statistics and logistic regression analyses were used to describe the whole cohort. RESULTS: Of all, 792 (23%) men with at least one abnormal WHO semen parameter but without any identified aetiologic factor for infertility, were considered as idiopathic infertile men. Of 792, 418 (52.7%) men had SDF ≥30%. Men with pathologic SDF were older (p = .02), had higher Follicle-stimulating hormone (FSH) (p = .04) but lower total testosterone (p = .03) values than those with SDF <30%. The homoeostatic model assessment index for insulin resistance (HOMA-IR) was higher in men with SDF ≥30% (p = .01). Idiopathic infertile men with SDF ≥30% presented with lower sperm concentration (p < .001) and lower progressive sperm motility (p < .01) than those with SDF < 30%. Logistic regression analysis revealed that older age (OR: 1.1, p = .02) and higher HOMA-IR score (OR: 1.8, p = .03) were associated with SDF ≥ 30%, after accounting for FSH and sperm concentration values. CONCLUSIONS: Approximately half of infertile men categorized as idiopathic had pathologic SDF values. Idiopathic infertile men with pathologic SDF showed worse clinical, hormonal and semen parameters than those with normal SDF values. These results suggest that including SDF testing could be clinically relevant over the real-life management work-up of infertile men.

Oral preparation of hyaluronic acid, chondroitin sulfate, N-acetylglucosamine, and vitamin C improves sexual and urinary symptoms in participants with recurrent urinary tract infections: a randomized crossover trial.

BACKGROUND: Intravesical instillation of hyaluronic acid (HA) has been associated with reduced sexual dysfunction in participants with recurrent urinary tract infections (rUTIs), but the efficacy of an oral treatment has never been investigated. AIM: To investigate the efficacy of an oral preparation of HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C in improving sexual and urinary symptoms in a cohort of reproductive-age participants with rUTI. METHODS: In a monocentric randomized crossover pilot trial, participants with rUTI who were referred to our institute between March 2022 and April 2023 were randomized 1:1 in 2 groups: intervention vs control. All participants had an oral preparation of cranberry, D-mannose, propolis extract, turmeric, and Boswellia twice a day for 3 months. The intervention group also included an oral preparation of HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C once a day for 3 months. Crossover of treatment occurred at 3 months for an additional 3 months. At baseline and 3 and 6 months, participants were evaluated clinically and with the International Prostate Symptom Score (IPSS) and Female Sexual Function Index (FSFI). Descriptive statistics and logistic regression models tested the impact of the intervention on urinary and sexual symptoms at each follow-up assessment. OUTCOMES: Improvement in sexual and urinary symptoms as measured by the FSFI and IPSS. RESULTS: Overall, 27 (54%) participants had an FSFI score <26.5 at enrollment. At 3 months, FSFI scores were higher in the intervention group vs control (P < .001), but IPSS scores were lower (P = .03). After crossover of treatment, FSFI and IPSS scores remained stable in the intervention group. However, after crossover, the control group showed a significant improvement in IPSS and FSFI scores (all P < .01) vs the 3-month assessment. At last follow-up, urinary and sexual symptoms were comparable between groups. In logistic regression analyses, the intervention group was associated with early improvement in sexual symptoms (odds ratio, 3.9; P = .04) and urinary symptoms (odds ratio, 5.1; P = .01) after accounting for clinical confounders. CLINICAL IMPLICATIONS: Combination treatment with HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C is effective if started immediately or even after a few months from symptoms in participants with rUTI. STRENGTHS AND LIMITATIONS: The main limitation is the lack of long-term follow-up. CONCLUSION: The oral formulation of HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C could be an effective therapy against urinary and sexual distress in participants with rUTI (NCT06268483; ClinicalTrials.gov).

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.

Prevalence and predictors of stone passage after double J stenting for symptomatic ureteral stones: a cross-sectional, real-life study.

PURPOSE: To evaluate the rate of and predictors of stone passage (SP) after urgent retrograde stenting for symptomatic ureteral stones. METHODS: We retrospectively analysed data from 249 consecutive patients presenting to the emergency department for symptomatic ureteral stones and treated with retrograde stenting. Demographic, clinical and laboratory characteristics were collected. Stones parameters were collected before stenting and SP was evaluated at 1 month with computerized tomography. Descriptive statistics and logistic regression models tested the association between predictors and SP. RESULTS: Overall, median (IQR) age and stone diameter were 56 (45-68) years and 7.1 (4.4-9.8) mm, respectively. Stones were located in the proximal, mid and distal ureter in 102 (41.0%), 48 (19.3%) and 99 (39.8%) cases. SP was observed in 65 (26.2%) individuals. Stone diameter (3.2 vs. 7.7 mm, p < 0.001) and stone density (416 vs. 741, p < 0.001) were lower and a higher rate of distal stones (76.9% vs. 26.7%, p < 0.001) was found in the SP group compared to that with persistent stones. Multivariable logistic regression analysis showed that distal ureteral stone location (OR 7.9, p < 0.01) and lower HU (OR 0.9, p < 0.01) were associated with SP, after accounting for stone volume. Patients with a distal stone of 500 HU had a 75% probability of SP. CONCLUSION: Stone passage occurred in 26% of patients with indwelling stent due to symptomatic ureteral stones. Lower stone density and distal stone location were independent predictors of stone passage. Patients with these criteria should be managed with follow-up imaging and stent removal instead of ureteroscopy.

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.

Transient ureteral obstruction after mini-percutaneous nephrolithotomy is associated with stone volume and location: results from a single-center, real-life study.

PURPOSE: To evaluate the rate of and predictors of ureteral obstruction after mini-percutaneous nephrolithotomy (mPCNL) for kidney stones. METHODS: We analyzed data from 263 consecutive patients who underwent mPCNL at a single tertiary referral academic between 01/2016 and 11/2022. Patient's demographics, stone characteristics, and operative data were collected. A nephrostomy tube was placed as the only exit strategy in each procedure. On postoperative day 2, an antegrade pyelography was performed to assess ureteral canalization. The nephrostomy tube was removed if ureteral canalization was successful. Descriptive statistics and logistic regression models were used to identify factors associated with a lack of ureteral canalization. RESULTS: Overall, median (IQR) age and stone volume were 56 (47-65) years and 1.7 (0.8-4.2) cm3, respectively. Of 263, 55 (20.9%) patients showed ureteral obstruction during pyelography. Patients without ureteral canalization had larger stone volume (p < 0.001), longer operative time (p < 0.01), and higher rate of stones in the renal pelvis (p < 0.01) than those with normal pyelography. Length of stay was longer (p < 0.01), and postoperative complications (p = 0.03) were more frequent in patients without ureteral canalization. Multivariable logistic regression analysis revealed that stone volume (OR 1.1, p = 0.02) and stone located in the renal pelvis (OR 2.2, p = 0.04) were independent predictors of transient ureteral obstruction, after accounting for operative time. CONCLUSION: One out of five patients showed transient ureteral obstruction after mPCNL. Patients with a higher stone burden and with stones in the renal pelvis are at higher risk of inadequate ureteral canalization. Internal drainage might be considered in these cases to avoid potential complications.

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.

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.

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.

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.

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.

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.

The statistical foundation of the reference population for semen analysis included in the sixth edition of the WHO manual: a critical reappraisal of the evidence.

In the most recent version of the 'WHO Laboratory Manual For The Examination And Processing Of Human Semen', the updated target population used to infer reference values included 3589 fertile subjects, representative of 12 countries and 5 continents, and 10 studies. We have critically evaluated the newly proposed distribution of semen examination results using an approach borrowed from clinical chemistry laboratories and based on the recommendations of the International Federation of Clinical Chemistry for estimation of reference intervals. Surprisingly, most prerequisites to produce common reference intervals through multicentric data were not met. Moreover, when we assessed with the bootstrap method the descriptive reference values obtained from raw data of the 10 individual studies for sperm concentration, sperm number, motility and normal forms, we found that none of the populations was completely correctly described by the reference centiles. We concluded that aggregated data used to build the reference distribution cannot be considered to originate from the same population, and this can result from real differences among individuals or different methodological approaches used in the various studies. Transferability conditions across studies did not seem to have been met. Our findings strengthen the relevance of concerns regarding the use of reference populations in the World Health Organization manual to discriminate between fertile and infertile men.

Cardiovascular Morbidity and Mortality in Men - Findings From a Meta-analysis on the Time-related Measure of Risk of Exogenous Testosterone.

BACKGROUND: In the context of established male hypogonadism, testosterone therapy (TTh) has been employed to regain physiologic levels of circulating testosterone and improve sexual function and overall quality of life. AIM: To assess the risk of cardiovascular disease and mortality as time-dependent outcomes in treated vs TTh untreated hypogonadal men. METHODS: A meta-analysis using weighted time-related measure of risk (hazard ratios (HRs)) for each of the outcome for all included studies was performed. Studies investigating male adults (≥18 years old) diagnosed with hypogonadism and divided into 2 arms (a treatment arm [any TTh] and a control arm [observation or placebo]) and assessing the risk of death and/or cardiovascular events were included. Single arm, non-comparative studies were excluded as well as studies that did not report the HRs for the chosen outcomes. This systemic review was registered on PROSPERO (CRD42022301592) and performed according to MOOSE and PRISMA guidelines. OUTCOMES: Overall mortality and cardiovascular events of any type. RESULTS: Overall, 10 studies were included in the meta-analysis, involving 179,631 hypogonadal men. Hypogonadal men treated with TTh were found to be at lower mortality risk from all causes relative to the control (observation or palcebo) arm (HR: 0.70; 95% Confidence Interval [CI]: 0.54-0.90; P < .01), whilst any unfavorable effect of TTh in hypogonadal men in terms of cardiovascular events compared to untreated/observed hypogonadal men was found (HR: 0.98; 95% CI 0.73-1.33; P = .89). CLINICAL IMPLICATIONS: TTh in hypogonadal men might play a role in reducing the overall risk of death without increasing cardiovascular events risk. STRENGTHS & LIMITATION: Main limitations are represented by the high heterogeneity among the studies in terms of included population, definition for hypogonadism, type of TTh, definition of cardio-vascular event used, and the length of follow-up. CONCLUSION: According to time-related measures of risk only, an increased risk of long-term morbidity and early mortality for untreated hypogonadal men was depicted, further outlining the clinical importance and safety of TTh in true hypogonadal men, with the urgent need of collecting long-term follow-up data. Fallara G, Pozzi E, Belladelli F, et al. Cardiovascular Morbidity and Mortality in Men - Findings From a Meta-analysis on the Time-related Measure of Risk of Exogenous Testosterone. J Sex Med 2022;19:1243-1254.

Urologists are optimistic surgeons: prevalence and predictors of discordance between intraoperative stone-free rate and cross-sectional imaging evaluation after vacuum-assisted mini-percutaneous nephrolithotomy.

PURPOSE: To assess how accurate are urologists in predicting stone-free status (SFS) after vacuum-assisted mini-PCNL (vamPCNL) compared to computed tomography (CT) and clinical predictors of discordant SFS. METHODS: Data from 235 patients who underwent vamPCNL were analysed. Patient's demographics, stones' characteristics and operative data were recorded. SFS was evaluated intraoperatively by the treating urologist (iSFS) and with non-contrast CT 3 months after vamPCNL (ctSFS). SFS was defined as no residual stones. Stone complexity was scored with the Guy's score. Descriptive statistics and logistic regression models were used to identify clinical factors associated with discordant SFS (namely iSFS not confirmed at CT). RESULTS: iSFS and ctSFS were 88.5% and 65.5%, respectively, with 54 (23%) cases resulting in discordant evaluation of SFS between the surgeon and CT imaging. Patients with discordant SFS had larger stone volume (p < 0.001), higher rate of multiple stones (p = 0.03) and higher rate of multiple calyceal groups affected by stones (p < 0.001) than those with concordant SFS. The use of flexible ureteroscopes to look for residual stones after lithotripsy was more frequently reported in cases with concordant SFS (p = 0.001). Multivariable logistic regression analysis revealed that stones in > 2 calyceal groups (OR 10.2, p < 0.001), Guy's score II (OR 5.8, p < 0.01) and not using flexible ureteroscopes after lithotripsy (OR 2.9, p = 0.02) were independent predictors of discordant SFS. CONCLUSION: One out of five patients is erroneously considered SF after vamPCNL. Urologist should carefully evaluate patients with multiple calyceal stones and consider using flexible ureteroscopes to complete lapaxy of migrated fragments in order to improve their prediction of SFS.

The comprehensive complication index as a tool for reporting the burden of complications after mini-percutaneous nephrolithotomy: is it time to leave the Clavien-Dindo classification behind?

PURPOSE: To validate the comprehensive complication index (CCI) for mini-percutaneous nephrolithotomy (mPCNL). METHODS: Data from 287 patients who underwent mPCNL were analyzed. Complications after mPCNL were classified using both the CCI and the Clavien-Dindo classification (CDC). Descriptive statistics and linear/logistic regression analyses detailed the association between clinical predictors and mPCNL outcomes. RESULTS: After mPCNL, 83 (28.9%) patients had complications, of which 12 (4.2%) patients with multiple complications had a higher CCI score compared to the traditional CDC system accounting only for the highest grade. The CCI enabled a more accurate prediction of length of stay (LOS) than CDC (CCI: r = 0.32; p < 0.01 vs. CDC: r = 0.26; p = 0.01). Patients with multiple complications had higher stone volume (p = 0.02), longer operative time and LOS (all p < 0.01). A higher rate of post-operative hospital readmission (33.3% vs. 9.9%, p = 0.02) and lower rate of stone free (33.3% vs. 64.7%, p = 0.04) were found in patients with multiple complications than in those with single complication. Linear regression analysis revealed that multiple complications were associated with longer LOS (p < 0.001) after accounting for BMI and stone volume. Similarly, having multiple complications was associated with fivefold higher risk of readmission (p = 0.02). CONCLUSION: The CCI is a valuable metric for assessing post-operative complications after mPCNL. The cumulative CCI is a better predictor of LOS than the CDC for mPCNL. Minor complications not captured by the highest CDC score are relevant since patients with multiple complications have longer LOS and higher rate of readmission than those with single ones.

Cost analysis between mini-percutaneous nephrolithotomy with and without vacuum-assisted access sheath.

PURPOSE: To perform a cost analysis between vacuum-assisted percutaneous nephrolithotomy (vmPCNL) and minimally invasive PCNL (MIP) and explore potential predictors of costs associated with the procedures. METHODS: We analyzed data from 225 patients who underwent vmPCNL or MIP at a single tertiary referral academic center between January 2016 and December 2020. We collected patients' demographics, peri-and postoperative data and detailed expense records. After propensity score matching, 108 (66.7%) vmPCNL and 54 (33.3%) MIP procedures were analyzed. Descriptive statistics assessed differences in clinical and operative parameters. Univariable and multivariable linear regression models tested the association between clinical variables and costs. RESULTS: Operative time (OT) was shorter for vmPCNL, and the use of additional instruments to complete litholapaxy was more frequent in MIP (all p ≤ 0.01). Length of stay (LOS) was longer for MIP patients (p = 0.03) and the stone-free (SF) rate was higher after vmPCNL (p = 0.04). The overall instrumentation cost was higher for vmPCNL (p < 0.001), but total procedural costs were equivalent (p = 0.9). However, the overall cost for the hospitalization was higher for MIP than vmPCNL (p = 0.01). Univariable linear regression revealed that patient's comorbidities, OT, any postoperative complication and LOS were associated with hospitalization costs (all p < 0.001). Multivariable linear regression analysis revealed that LOS and OT were associated with hospitalization costs (all p < 0.001), after accounting for vmPCNL procedure, patients' comorbidities, and complications. CONCLUSION: vmPCNL may represent a valid option due to clinical and economic benefits. Shorter OT, the lower need for disposable equipment and the lower complication rate reduced procedural and hospitalization costs.

Normal sperm parameters per se do not reliably account for fertility: A case-control study in the real-life setting.

A proportion of men are infertile despite having normal medical history/physical examination and normal semen analysis. We aimed to assess whether normal sperm parameters per se account for male factor fertility. 1,957 infertile men were compared with 103 age-comparable fertile controls. Semen analysis was based on 2010 World Health Organization reference criteria. Of all, 12.1% of infertile men and 40.8% of fertile men presented with normal sperm parameters. Among fertile men, 36.9% had isolated sperm abnormalities and 22.3% men showed two or more concomitant sperm abnormalities. Serum total testosterone was higher in infertile men with normal sperm parameters compared to those with ≥2 sperm abnormalities or azoospermia, but similar to those with isolated sperm abnormalities (p ≤ .001). Circulating hormones were similar among sperm parameters groups in fertile men. At multivariable analyses, testicular volume (OR 1.12, p ≤ .001) and FSH (OR 0.8, p ≤ .001) were associated with normal sperm parameters. Overall, the longer the infertility period, the greater the number of sperm parameters abnormalities (p < .01). In conclusion, we found that 12% of infertile men and only 41% of fertile men present with normal sperm parameters. Normal sperm parameters per se do not reliably account for fertility in the real-life setting.

Nomenclature in thulium laser treatment of benign prostatic hyperplasia: it's time to pull the rabbit out of the hat.

We performed a narrative review with the focus on laser settings and surgical procedure with thulium laser. Our primary goal was to define the most valid settings of each surgical procedure to overcome the inconsistency about nomenclature of thulium surgery and to ensure comparability of future publications. A literature search of articles on thulium laser treatment of benign prostatic hyperplasia (BPH) was conducted between 2009 and 2019. We proposed a new classification standard for laser settings and associated surgical procedure. Each article was analyzed and categorized as concordant or discordant referring to the new classification. In total, 74 papers were included in this narrative review. Overall, 43% and 42% of included studies reported discordant laser parameters and surgical description, respectively. Most of the studies on vaporization were categorized as discordant because they reported a medium/low laser setting instead of high power. Conversely, 93.3% of studies on enucleation were deemed as discordant for laser setting because they reported high power parameters instead of medium-low power setting. Most of the studies on laser enucleation and vapo/enucleation were considered discordant for surgical procedure since authors did not mention the use of mechanical vs. laser method for enucleation. The current literature lacks a uniform definition and standardization of the terminology of thulium laser settings and surgical techniques to guarantee comparability between different approaches. We found a huge heterogeneity in 10 years of surgery with thulium laser. We proposed a new classification of laser setting and procedural description for categorization of thulium laser surgery for BPH.