Trends and incidence of reported events associated with ureteral stents: an analysis of the food and drug administration's manufacturer and user facility device experience (MAUDE) database.

PURPOSE: Aim of this study is to summarize medical device reports (MDRs) between 2012 and 2022 relating to ureteral stents within the Manufacturer and User Facility Device Experience (MAUDE) database maintained by The Food and Drug Administration (FDA). METHODS: MAUDE was analyzed for all MDRs relating to each FDA-approved ureteral stent. Event descriptions were reviewed and characterized into specific event types. Outcome measures include specific ureteral stent and reported events as detailed by the MDRs. Data is presented as number of specific event/total events. Pooled Relative risk was used to compare data. RESULTS: 2652 reports were retrieved in 10 years and a progressive rise in reported events was recorded. 831/2652 (31%) were reported as injury while 1810/2652 (68%) as malfunction of the ureteral stent and 4 events of death. The most frequently reported adverse events (AEs) were stent break (627/2652: 23%); material problems (384/2652: 14%); calcification (222/2652: 8%); difficulty to insert, advance or remove the device (155/2652: 6%). Bard stents were associated with most material problems (19%), Resonance stents were associated with most difficulty to insert, advance or remove the device (9%) and calcification (15%) while filiform double pigtail stent set were associated with most breakage reports (56%) when compared to the other stents (PRR > 1, p < 0,05). CONCLUSIONS: According to MAUDE database the most frequent complications related to ureteral stents are breakage, material problems, calcification and difficulty to insert/advance/remove the device. As well Resonance ureteral stents seem to be associated with a higher risk of device problems.

Post-voided residual urine ratio as a predictor of bladder outlet obstruction in men with lower urinary tract symptoms: development of a clinical nomogram.

PURPOSE: To confirm the correlation between post-void residual urine ratio (PVR-R) and BOO diagnosed by pressure-flow studies (PFS) in males with lower urinary tract symptoms (LUTS) and to develop a clinical nomogram. METHODS: A consecutive series of patients aged 45 years or older with non-neurogenic LUTS were prospectively enrolled. Patients underwent standard diagnostic assessment for BOO including International Prostatic Symptoms Score, uroflowmetry, urodynamic studies, suprapubic ultrasound of the prostate, and ultrasound measurements of the bladder wall thickness (BTW). PVR-R was defined as follows: PVR-R = (PVR/total Bladder Volume [BV]) × 100). Logistic regression analysis was used to investigate predictors of pathological bladder emptying (BOO) defined as Schafer > II. A nomogram to predict BOO based on the multivariable logistic regression model was then developed. RESULTS: Overall 335 patients were enrolled. Overall, 131/335 (40%) presented BOO on PFS. In a multivariable logistic age-adjusted regression model BWT (odds ratio [OR]: 2.21 per mm; 95% confidence interval [CI], 1.57-3.09; p = 0.001), PVR-R (OR: 1.02 per %; 95% CI, 1.01-1.03; p = 0.034) and prostate volume (OR: 0.97 per mL; 95% CI, 0.95-0.98; p = 0.001) were significant predictors for BOO. The model presented an accuracy of 0.82 and a clinical net benefit in the range of 10-90%. CONCLUSIONS: The present study confirms the important role of PVR-ratio in the prediction of BOO. For the first time, we present a clinical nomogram including PVR-ratio for the prediction of BOO.

Serum levels of chromogranin are not predictive of poorly differentiated prostate cancer: Results from a multicenter radical prostatectomy cohort.

BACKGROUND: Recently a possible link between elevated Chromogranin A (CgA) levels and poorly differentiated prostate cancer has been proposed. The aim of our study was to explore the association of CgA levels and the risk of poorly differentiated prostate cancer (PCa) in men undergoing radical retropubic prostatectomy (RRP). MATERIALS AND METHODS: From 2012 onwards, 335 consecutive men undergoing RRP for PCa at three centers in Italy were enrolled into a prospective database. Body mass index (BMI) was calculated before RRP. Blood samples were collected and tested for total prostate-specific antigen (PSA) levels and chromogranin A (CgA). We evaluated the association between serum levels of CgA and upstaging and upgrading using logistic regression analyses. RESULTS: Median age and preoperative PSA levels were 65 years (interquartile range [IQR]: 60-69) and 7.2 ng/ml (IQR: 5.3-10.4), respectively. Median BMI was 26.1 kg/m2 (IQR: 24-29) with 56 (16%) obese (BMI ≥ 30 kg/m2 ). Median CgA levels were 51 (39/71). Overall, 129/335 (38,5%) presented an upstaging, and 99/335 (30%) presented an upgrading. CgA was not a predictor of upstaging or upgrading on RP. CONCLUSIONS: In our multicenter cohort of patients, CgA is not a predictor of poorly differentiated PCa on radical prostatectomy. According to our experience, CgA should not be considered a reliable marker to predict poorly differentiated or advanced prostate cancer.

Development of a nomogram predicting the probability of stone free rate in patients with ureteral stones eligible for semi-rigid primary laser uretero-litothripsy.

PURPOSE: Few tools are available to predict uretero-lithotripsy outcomes in patients with ureteral stones. Aim of our study was to develop a nomogram predicting the probability of stone free rate in patients undergoing semi-rigid uretero-lithotripsy (ULT) for ureteral stones. METHODS: From January 2014 onwards, patients undergoing semi-rigid Ho: YAG laser uretero-lithotripsy for ureteral stones were prospectively enrolled in two centers. Patients were preoperatively evaluated with accurate clinical history, urinalysis and renal function. Non-contrast CT was used to define number, location and length of the stones and eventually the presence of hydronephrosis. A nomogram was generated based on the logistic regression model used to predict ULT success. RESULTS: Overall, 356 patients with mean age of 54 years (IQR 44/65) were enrolled. 285/356 (80%) patients were stone free at 1 month. On multivariate analysis single stone (OR 1.93, 95% CI 1.05-3.53, p = 0.034), stone size (OR 0.92, 95% CI 0.87-0.97, p = 0.005), distal position (OR 2.12, 95% CI 1.29-3.48, p = 0.003) and the absence of hydronephrosis (OR 2.02, 95% CI 1.08-3.78, p = 0.029) were predictors of success and these were used to develop a nomogram. The nomogram based on the model presented good discrimination (area under the curve [AUC]: 0.75), good calibration (Hosmer-Lemeshow test, p > 0.5) and a net benefit in the range of probabilities between 15 and 65%. Internal validation resulted in an AUC of 0.74. CONCLUSIONS: The implementation of our nomogram could better council patients before treatment and could be used to identify patients at risk of failure. External validation is warranted before its clinical implementation.

The role of bladder wall thickness in the evaluation of detrusor underactivity: Development of a clinical nomogram.

AIMS: The aim of our study was to investigate noninvasive predictors for detrusor underactivity (DUA) in male patients with lower urinary tract symptoms (LUTS) and benign prostatic enlargement (BPE). METHODS: A consecutive series of patients aged 45 years or older with non-neurogenic LUTS were prospectively enrolled. Patients underwent standard diagnostic assessment including International Prostatic Symptoms Score, uroflowmetry, urodynamic studies (cystometry and pressure-flow studies), transrectal ultrasound of the prostate, and ultrasound measurements of the bladder wall thickness (BWT). Logistic regression analysis was used to investigate predictors of DUA, defined as a bladder contractility index < 100 mm H2 O. A nomogram was developed based on the multivariable logistic regression model. RESULTS: Overall 448 patients with a mean age of 66 ± 11 years were enrolled. In a multivariable logistic age-adjusted regression model BWT (odds ratio [OR]: 0.50 per mm; 95% confidence interval [CI], 0.30-0-66; P = .001) and Qmax (OR: 0.75 per mL/s; 95% CI, 0.70-0.81; P = .001) were significant predictors for DUA. The nomogram based on the model presented good discrimination (area under the curve [AUC]: 0.82), good calibration (Hosmer-Lemeshow test, P > .05) and a net benefit in the range of probabilities between 10% and 80%. CONCLUSIONS: According to our results, BWT and Qmax can noninvasively predict the presence of DUA in patients with LUTS and BPE. Although our study should be confirmed in a larger prospective cohort, we present the first available nomogram for the prediction of DUA in patients with LUTS.

Metabolic syndrome and smoking are associated with persistence of nocturia after transurethral resection of the prostate.

AIMS: The aim of our study was to evaluate the relationship between smoking, metabolic syndrome (MetS) and persistence of nocturia in patients with moderate/severe nocturia (nocturia episodes ≥2), lower urinary tract symptoms (LUTSs), and benign prostatic enlargement (BPE) undergoing transurethral resection of the prostate (TURP). METHODS: From 2015 onward, a consecutive series of patients with moderate/severe nocturia (nocturia episodes ≥2), LUTS, and BPE undergoing TURP were prospectively enrolled. Medical history, physical examination, and smoking status were recorded. MetS was defined according to Adult Treatment Panel III. Moderate/severe persistent nocturia after TURP was defined as nocturia episodes ≥2. Binary logistic regression analysis was used to evaluate the risk of persisting nocturia. RESULTS: One hundred two patients were enrolled with a median age of 70 years (interquartile range: 65/73). After TURP, moderate/severe nocturia was reported in 43 of 102 (42%) of the patients. Overall 40 of 102 (39%) patients presented a MetS, and out of them, 23 of 40 (58%) presented a moderate/severe persistent nocturia after TURP ( P = .001). Overall 62 of 102 (61%) patients were smokers, and out of them, 32 of 62 (52%) presented moderate/severe persistent nocturia after TURP ( P = .034). On multivariate analysis, prostate volume, MetS, and smoking were independent risk factors for moderate/severe persistent nocturia after TURP. CONCLUSION: In our single-center study, MetS and smoking increased the risk of moderate/severe persistent nocturia after TURP in patients with LUTS-BPE. Although these results should be confirmed, and the pathophysiology is yet to be completely understood, counseling smokers and MetS patients about the risk of postoperative persistent nocturia is warranted.

Repeat prostate-specific antigen (PSA) test before prostate biopsy: a 20% decrease in PSA values is associated with a reduced risk of cancer and particularly of high-grade cancer.

OBJECTIVES: To analyse the impact of repeating a prostate-specific antigen (PSA) level assessment on prostate biopsy decision in a cohort of men undergoing prostate biopsy. PATIENTS AND METHODS: From 2015 onwards, we consecutively enrolled, at a single institution in Italy, men undergoing 12-core transrectal ultrasonography-guided prostate needle biopsy. Indication for prostate biopsy was a PSA level of ≥4 ng/mL. Demographic, clinical, and histopathological data were collected. The PSA level was tested at enrolment (PSA1 ) and 4 weeks later on the day before biopsy (PSA2 ). Variations in PSA level were defined as: stable PSA2 within a 10% variation, stable PSA2 within a 20% variation, PSA2 decreased by ≥10%, PSA2 decreased by ≥20%, PSA2 increased by ≥10%, PSA2 increased by ≥20%, and PSA2 <4 ng/mL. Percentages and multinomial logistic regression were used to analyse biopsy outcomes. High-grade cancer was defined as Grade group ≥3. RESULTS: Overall, 331 patients were enrolled. Prostate cancer was diagnosed in 153/331 (46%) patients and of them 80/153 (52%) had high-grade disease. When compared to the rest of the population, patients with a stable PSA within 20% variation had a higher risk of prostate cancer (odds ratio [OR] 1.80, P < 0.05) and high grade disease (OR 2.56, P < 0.05), patients with a PSA2 decreased by ≥20% had a lower risk of prostate cancer (OR 0.37, P < 0.05) and high grade disease (OR 0.13, P < 0.05), whilst patients with a PSA2 increased by ≥10% had an increased risk of high-grade prostate cancer (OR 1.93, P < 0.05). When PSA returned to normal values (<4 ng/mL) both risks of prostate cancer and high-grade disease were reduced (OR 0.33 and 0.01, respectively, P = 0.001). CONCLUSION: In a cohort of Italian men undergoing prostate biopsy, a reduction of ≥20% in PSA levels significantly reduced the risk of high-grade prostate cancer. Further multicentre studies should validate our present results.

No clinical benefit from sequential combination of mitomycin C plus bacillus Calmette-Guérin (BCG) than BCG alone in the adjuvant treatment of high risk non muscle invasive bladder cancer: result of a planned interim analysis of a prospective randomized trial.

BACKGROUND: The aim of this study was to evaluate whether the sequential use of Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) is superior to BCG alone in reducing the risk of disease recurrence in patients with non-muscle invasive bladder cancer (NMIBC) with high risk of progression. METHODS: Prospective randomized trial was conducted from March 2021 to March 2023 and included 72 patients with high risk NMIBC. Trial registration number: NCT03790384; EUDRACT Number: 2017-004540-37. Thirty-one patients underwent to BCG alone and forty-one to MMC plus BCG during the induction course. The BCG schedule comprised six weekly instillation of 81 mg Connaught strain BCG as the induction course, followed by a further three-monthly instillation at three, six and twelve months, as the maintenance course. Forty mg of MMC were administered the day prior to each weekly BCG instillation in BCG plus MMC arm. A planned interim analysis was carried out in June 2023, at the end of the 12mo follow-up period. RESULTS: Six out of thirteen 6/31(19.3%) and 10/41 (24.4%) patients experienced recurrence in BCG and BCG plus MMC group (P=0.611), respectively. BCG plus MMC did not improve Disease Free Interval (HR: 1.23 95% CI:0.46-3.50; P=0.640). Patients receiving sequential treatment experienced similar AEs (P>0.05) and more urinary symptoms (P<0.05). CONCLUSIONS: This interim pre-planned analysis suggested absence of clinical advantages in terms of disease recurrence rate when MMC is administered one day prior to BCG during induction course.

Medications mostly associated with hematuria: assessment of the EudraVigilance and Food and Drug Administration pharmacovigilance databases entries.

BACKGROUND: Drugs may have a direct causative role in triggering hematuria. The range of medications which may be responsible for hematuria is wide, but little is known on those which are most frequently involved. The aim of our study was to identify and compare drugs mostly related with hematuria. METHODS: The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database and the EudraVigilance (EV) database were queried to identify the drugs which were associated the most with hematuria individual reports till 30 September 2021. Rivaroxaban, aspirin, warfarin sodium, clopidogrel bisulfate, dabigatran etexilate mesylate, apixaban, warfarin, cyclophosphamide, lansoprazole, enoxaparin sodium, and ibuprofen were analyzed. Analysis per gender, age and severity was performed. Disproportional analysis was performed to compare drugs. RESULTS: Overall, 15,687 reports of hematuria were recorded in the FDA database and 15 007 in the EV database. Rivaroxaban and Warfarin appear to be the most dangerous medications in terms of hematuria when compared to the other medications (PRR>1, P<0.05) while apixaban is the safest one (PRR<1, P<0.05) when compared to the other medications. In terms of severity only 162/15 007 (1.08%) were fatal. Between the drugs analyzed cyclophosphamide 7.2%, enoxaparin (3%) and dabigatran (2.5%) presented a higher number of fatal hematuria episodes when compared to the other drugs (<1%). CONCLUSIONS: Anticoagulants and antiplatelets are more frequently related to hematuria episodes however some differences exist between them. Particularly warfarin and rivaroxaban should be prescribed with caution in patients at increased risk of hematuria. Prescribers should inform those treated with these medications about the risk of hematuria and its sequelae.

Quality of information and appropriateness of Open AI outputs for prostate cancer.

Chat-GPT, a natural language processing (NLP) tool created by Open-AI, can potentially be used as a quick source for obtaining information related to prostate cancer. This study aims to analyze the quality and appropriateness of Chat-GPT's responses to inquiries related to prostate cancer compared to those of the European Urology Association's (EAU) 2023 prostate cancer guidelines. Overall, 195 questions were prepared according to the recommendations gathered in the prostate cancer section of the EAU 2023 Guideline. All questions were systematically presented to Chat-GPT's August 3 Version, and two expert urologists independently assessed and assigned scores ranging from 1 to 4 to each response (1: completely correct, 2: correct but inadequate, 3: a mix of correct and misleading information, and 4: completely incorrect). Sub-analysis per chapter and per grade of recommendation were performed. Overall, 195 recommendations were evaluated. Overall, 50/195 (26%) were completely correct, 51/195 (26%) correct but inadequate, 47/195 (24%) a mix of correct and misleading and 47/195 (24%) incorrect. When looking at different chapters Open AI was particularly accurate in answering questions on follow-up and QoL. Worst performance was recorded for the diagnosis and treatment chapters with respectively 19% and 30% of the answers completely incorrect. When looking at the strength of recommendation, no differences in terms of accuracy were recorded when comparing weak and strong recommendations (p > 0,05). Chat-GPT has a poor accuracy when answering questions on the PCa EAU guidelines recommendations. Future studies should assess its performance after adequate training.

Post-Voided Residual Ratio Does Not Predict Trifecta Outcome after Transurethral Resection of Prostate.

The purpose of this study was to assess the importance of the post-void residual (PVR) ratio (PVR ratio) in achieving a favorable trifecta outcome for patients suffering from lower urinary tract symptoms and benign prostatic enlargement (LUTS-BPE) who undergo transurethral resection of the prostate (TURP). Starting from 2015, a series of patients with LUTS-BPE who underwent TURP were included in a forward-looking study. These patients were assessed using the international prostate symptom score (IPSS) screening tool, uroflowmetry, and a transrectal ultrasound to measure prostate volume (TRUS). Both the PVR urine volume and the PVR ratio (PVR-R), which is the PVR as a percentage of total bladder volume (voided volume + PVR), were measured. The assessment of outcomes was based on the trifecta favorable outcome, defined as meeting all of the following criteria: (1) absence of perioperative complications, (2) a postoperative IPSS of less than eight, and (3) a postoperative maximum urinary flow rate (Qmax) greater than 15 mL/s. A total of 143 patients were included, with a median age of 70 years (interquartile range 65-73). Of these, 58% (83/143) achieved a positive trifecta outcome. Upon conducting a multivariate analysis, both IPSS and Qmax were identified as predictors of a positive trifecta outcome, whereas the PVR-R did not prove to be an independent predictor. In summary, it was found that preoperative IPSS and Qmax are indicative of a trifecta outcome following TURP, whereas PVR-R is not.

Major adverse cardiovascular events related to phosphodiesterase 5 inhibitors: analysis of real-life data from Eudra-Vigilance database.

BACKGROUND: Phosphodiesterase 5 inhibitors (PDE5i) are the standard medical treatment for erectile dysfunction. Aim of our study was to evaluate the rate of major adverse cardiovascular events (MACE) reported during PDE5i treatment based on Eudra-Vigilance (EV) reports. METHODS: EV database is the system for managing and analyzing data on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European Economic Area. MACE are defined as non-fatal stroke, non-fatal myocardial infarction, non-fatal congestive heart failure, revascularization after aorto-coronary graft bypass and cardiovascular death. We recorded the number of MACE for sildenafil, tadalafil, vardenafil, avanafil per category and severity until 1st July 2023. Pooled Relative Risk (PRR) was used to compare data between drugs. RESULTS: Overall, 951 MACE events were reported. Most of them were observed in younger patients <65 years old (452/951 events, 48%). Overall, 377/8939 (4%) MACE events were observed for sildenafil, 221/5213 (4%) for tadalafil, 50/1029 (4%) for vardenafil and no events for avanafil. No significative differences were reported comparing sildenafil and tadalafil (PRR 0.71-0.99, IQR 0.61-1.35, P>0.05), neither sildenafil vs. vardenafil (PRR 0.68-0.79, IQR 0.43-1.55, P>0.05), neither tadalafil vs. vardenafil (PRR 0.77-0.95, IQR 0.64-1.30. P>0.05) even when compared for age. Comparison between different classes of age showed MACE were more frequent in patients younger than 65 years old taking sildenafil and tadalafil when compared to patients older than 85 years old (PRR 0.02-0.11. IQR 0.01-0.40. P<0.01) and when compared to patients in 65-85 class of age (PRR 0.02-0.12, IQR 0.01-0.95, P<0.01). CONCLUSIONS: Real life data is consistent with MACE related to PDE5i. PDE5is are infrequently (<5%) associated with MACE. However, risk seems higher in younger patients, particularly for sildenafil (452/951 events, 48%). Clinicians should consider these data when prescribing PDE5i especially in young patients.

Unraveling the Dietary Puzzle: Exploring the Influence of Diet, Nutraceuticals, and Supplements on Bladder Cancer Risk, Outcomes, and Immunotherapy Efficacy: Insights from the BLOSSOM Study and Beyond.

Bladder cancer is considered a global health concern characterized by significant morbidity and mortality rates. The complex relationship between diet and bladder cancer is examined, with a specific focus on the role of diet in risk, outcomes, and treatment efficacy. Attention is drawn to the burgeoning field of immunotherapy in bladder cancer treatment, and the possible influence of diet on its outcomes is explored. While evidence remains limited, prior studies in other cancer types have suggested a potential connection between diet and immunotherapy response. To address this knowledge gap, the ongoing BLOSSOM study is presented, which aims to investigate the link between dietary factors, lifestyle, and the effectiveness of immunotherapy in patients with non-muscle-invasive bladder cancer. Ongoing efforts to decipher the intricate relationship between diet and bladder cancer care are highlighted, emphasizing the quest to unravel the dietary puzzle for the improvement of bladder cancer management.

Residents and Consultants Have Equal Outcomes When Performing Transrectal Fusion Biopsies: A Randomized Clinical Trial.

The aim of our study was to compare the performance of residents vs. consultants in transrectal fusion prostate biopsies (FUS-PBs), as well as patient-reported comfort. Between January 2021 and October 2022, a consecutive series of patients undergoing FUS-PBs were randomized into two groups: (A) FUS-PBs performed by a consultant; (B) FUS-PBs performed by trained residents (>50 procedures). All patients underwent FUS-PBs with 12 systematic cores and 3/6 target cores. The detection rate and number of positive cores in the target lesion were compared between groups, and the patient's discomfort after the procedure was evaluated using the VAS scale. Overall, 140 patients with a median age of 72 years were enrolled. Overall, 69/140 (49.3%) presented prostate cancer and 53/69 (76.8%) presented a clinically significant cancer (Grade Group ≥ 2). Consultants presented a detection rate of 37/70 (52.9%) and residents a detection rate of 32/70 (45.7%) (p > 0.2); the mean number of positive cores in the index lesion was similar in both groups (1.5 vs. 1.1; p > 0.10). In terms of the patients' experiences, the procedure was well tolerated, with a median VAS score of 2 in both groups, with no statistically significant differences. Residents showed satisfactory outcomes in terms of detection rate, procedural time, and patient comfort when performing prostate biopsies. Residents, after adequate training, can safely perform prostate biopsies.

Open versus Minimally Invasive Partial Nephrectomy: Trends and Outcomes from a Wide National Population-Based Database.

Objectives: To investigate temporal trends and overall complication rates among open partial nephrectomy (OPN) and minimally invasive partial nephrectomy (MIPN), including the impact of social determinants of health (SDOH) on postoperative outcomes. Methods: Patients who underwent OPN or MIPN between 2011 and 2021 were retrospectively analyzed by using PearlDiver-Mariner, an all-payer insurance claims database. The International Classification of Diseases diagnosis and procedure codes were used to identify the type of surgical operation, patient's characteristics (age, sex, region, insurance plan), postoperative complications and SDOH, categorized in education, healthcare, environmental, social, and economic domains. Outcomes were compared using multivariable regression models. Results: Overall, 65,325 patients underwent OPN (n = 23,377) or MIPN (n = 41,948). OPN adoption declined over the study period, whereas that of MIPN increased from 24% to 34% (p = 0.001). The 60-day postoperative complication rate was 15% for the open and 9% for the minimally invasive approach. Approximately 16% and 11% of patients reported at least one SDOH at baseline for OPN and MIPN, respectively. SDOH were associated with higher odds of postoperative complications (OPN = OR: 1.11, 95% CI: 1.01-1.25; MIPN = OR: 1.31, 95% CI: 1.18-1.46). The open approach showed a significantly higher risk of postoperative complications (OR: 1.62, 95% CI: 1.54-1.70) compared to the minimally invasive one. Conclusions: Our findings confirm that MIPN is gradually replacing OPN, which carries a higher risk of complications. SDOH are significant predictors of postoperative complications following PN, regardless of the approach.

Medications Mostly Associated With Ejaculatory Disorders: Assessment of the Eudra-Vigilance and Food and Drug Administration Pharmacovigilance Databases Entries.

OBJECTIVE: To identify which medications are mostly associated with ejaculatory disorders through a disproportionality analysis. METHODS: The Food and Drug Administration Adverse Event Reporting System (FDA-FAERS) and the Eudra-Vigilance (EV) database were queried to identify medications more commonly associated to ejaculatory disorders from September 10, 2012 to June 1, 2023. Proportional Reported Ratios (PRRs) were computed for all the selected drugs. RESULTS: Overall, 7404 reports of ejaculatory disorders reports were identified, and of these, 6854 cases (92.6%) were attributed to ten specific medications. On FDA-FAERS and EV databases, Paroxetine and Tamsulosin were the main responsible of delayed ejaculation (103/448 events, 23.0%) and retrograde ejaculation (366/1033 events, 35.4%), respectively. Finasteride was mostly related to painful ejaculation and ejaculation failure, with 150 events (7.8%) and 735 events (38.4%) respectively. Within the group of high-risk medications, Sildenafil presented higher risk of ejaculatory disorders than Tadalafil (PRR=5.85 (95%CI 5.09-6.78), P < .01). CONCLUSION: Ten drugs were recognized to display significant reporting levels of ejaculatory disorders. Among them, Finasteride and Sildenafil were responsible for the most reports in FDA-FAERS and in EV databases, respectively. Physicians should thoroughly counsel patients treated with these drugs about the risk of ejaculatory disorders. Further integration into clinical trials is needed to enhance the applicability and significance of these results.

Renal Function Preservation in Purely Off-Clamp Sutureless Robotic Partial Nephrectomy: Initial Experience and Technique.

The aim of our study is to evaluate the effectiveness and safety of a sutureless off-clamp robot-assisted partial nephrectomy (sl-oc RAPN), particularly its impact on renal function. A multicenter study was conducted from April 2021 to June 2022. Patients diagnosed with a renal mass of >2 cm and a PADUA score of ≤6 consecutively underwent an sl-oc RAPN procedure. Tumor features, patients characteristics, and intraoperative outcomes were assessed. An evaluation of renal function was performed preoperatively, and again at 1 and 3 months after surgery by measuring the creatinine and blood urea nitrogen levels. The renal function of the two separate kidneys was assessed by a sequential renal scintigraphy performed before and at least 30 days after surgery. A total of 21 patients underwent an sl-oc RAPN. The median age was 64 years (IQR 52/70), the median tumor diameter was 40 mm (IQR 29/45), and the median PADUA score was 4 (3.5/5). The intraoperative outcomes included operative time (OT), 90 (IQR 74/100) min; estimated blood loss (EBL), 150 (IQR 50/300) mL; and perioperative complications, CD > 3 1(5%); only two patients presented positive surgical margins in their final histology (2/21, 10%). Compared to the preoperative value, a decrease in renal function was highlighted with a statistically significant median decrease of 10 mL/min (p < 0.01). The renal scintigraphy showed an overall decrease in renal function compared to the preoperative value, with a range in the operated kidney that varied from 0 to 15 mL/s and from 0% to 40%, with a median value of 4 mL/s and 12%. sl-oc RAPN is a safe procedure, with a minimal impact on kidney function alteration. This technique has proven effective in preserving renal function and maintaining optimal oncological outcomes with limited complications.

Purely Off-Clamp Sutureless Robotic Partial Nephrectomy for Novice Robotic Surgeons: A Multi-Institutional Propensity Score-Matched Analysis.

Objectives: To compare perioperative outcomes of patients treated with sutureless off-clamp robotic partial nephrectomy (sl-oc RAPN) by either a novice or an expert robotic surgeon at two different institutions. Methods: Data concerning two continuous series of patients with cT1-2N0M0 renal tumors treated with sl-oc RAPN either by a novice or an expert surgeon were extracted from prospectively populated institutional databases over the last 4 years. Perioperative outcomes as well as the baseline characteristics of patients and tumors were compared by using χ2 and Mann-Whitney tests for categorical and continuous variables, respectively. A 1:1 propensity match score analysis (PMSa) generated two homogeneous cohorts. Logistic regression analysis was performed to assess predictors of trifecta outcomes, defined as negative surgical margins, no Clavien-Dindo ≧ 3 grade complications, and no ≧ 30% postoperative eGFR reduction. Results: Overall, 328 patients were treated by an expert surgeon, while 40 were treated by a novice surgeon. After PMSa analysis, two cohorts of 23 patients each were generated, homogeneous for all baseline variables (p ≥ 0.07). Hospital stay was the only significantly different outcome observed between the two groups (5 days vs. 2 days; p < 0.001). No statistically significant differences were recorded when comparing trifecta outcomes (expert: 100% vs. novice: 87%; p = 0.07). In the logistic regression analysis, no statistically significant predictors of trifecta outcomes were recorded. Conclusions: sl-oc RAPN is a feasible and safe nephron sparing technique, even when performed by a novice robotic surgeon.

A Systematic Review of the Efficacy and Toxicity of Brachytherapy Boost Combined with External Beam Radiotherapy for Nonmetastatic Prostate Cancer.

CONTEXT: The optimum use of brachytherapy (BT) combined with external beam radiotherapy (EBRT) for localised/locally advanced prostate cancer (PCa) remains uncertain. OBJECTIVE: To perform a systematic review to determine the benefits and harms of EBRT-BT. EVIDENCE ACQUISITION: Ovid MEDLINE, Embase, and EBM Reviews-Cochrane Central Register of Controlled Trials databases were systematically searched for studies published between January 1, 2000 and June 7, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Eligible studies compared low- or high-dose-rate EBRT-BT against EBRT ± androgen deprivation therapy (ADT) and/or radical prostatectomy (RP) ± postoperative radiotherapy (RP ± EBRT). The main outcomes were biochemical progression-free survival (bPFS), severe late genitourinary (GU)/gastrointestinal toxicity, metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS), at/beyond 5 yr. Risk of bias was assessed and confounding assessment was performed. A meta-analysis was performed for randomised controlled trials (RCTs). EVIDENCE SYNTHESIS: Seventy-three studies were included (two RCTs, seven prospective studies, and 64 retrospective studies). Most studies included participants with intermediate-or high-risk PCa. Most studies, including both RCTs, used ADT with EBRT-BT. Generally, EBRT-BT was associated with improved bPFS compared with EBRT, but similar MFS, CSS, and OS. A meta-analysis of the two RCTs showed superior bPFS with EBRT-BT (estimated fixed-effect hazard ratio [HR] 0.54 [95% confidence interval {CI} 0.40-0.72], p < 0.001), with absolute improvements in bPFS at 5-6 yr of 4.9-16%. However, no difference was seen for MFS (HR 0.84 [95% CI 0.53-1.28], p = 0.4) or OS (HR 0.87 [95% CI 0.63-1.19], p = 0.4). Fewer studies examined RP ± EBRT. There is an increased risk of severe late GU toxicity, especially with low-dose-rate EBRT-BT, with some evidence of increased prevalence of severe GU toxicity at 5-6 yr of 6.4-7% across the two RCTs. CONCLUSIONS: EBRT-BT can be considered for unfavourable intermediate/high-risk localised/locally advanced PCa in patients with good urinary function, although the strength of this recommendation based on the European Association of Urology guideline methodology is weak given that it is based on improvements in biochemical control. PATIENT SUMMARY: We found good evidence that radiotherapy combined with brachytherapy keeps prostate cancer controlled for longer, but it could lead to worse urinary side effects than radiotherapy without brachytherapy, and its impact on cancer spread and patient survival is less clear.

Is EMA warning on quinolones and fluoroquinolones really assessed? An EudraVigilance database analysis.

BACKGROUND: On March 11th 2019, European Medicines Agency (EMA) issues a warning after a review of serious, disabling and potentially permanent adverse events (AEs), particularly on musculoskeletal and nervous system, with quinolone (QN) and fluoroquinolone (FQ) antibiotics. Aim of this study was to evaluate the effect of the EMA warning on the rate of AEs after QN and FQ treatments, reported in the EudraVigilance (EV) database. METHODS: EV database is the system for managing and analyzing information on suspected AEs to medicines which have been authorized or being studied in clinical trials in the European Economic Area (EEA). We retrospectively explored the effect of FQs and QNs on musculoskeletal and nervous system from the EMA warning up to now (21 months) and compared these results with the 21 months before the EMA warning. RESULTS: Main part of AEs in EV database were reported for ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin. Ciprofloxacin total AEs before 21 months till 12 months of EMA warning were 2763. 12 months before EMA Warning they were 2935. Twelve months after EMA Warning they were 3419. Between 12 months till 21 months they were 3174. Musculoskeletal disorders were respectively 574 (21% of the total) 21 months before, 558 (19%) 12 months before, 1048 (31%) after 12 months, 540 (17%) after 21 months of EMA Warning. Nervous system disorders were respectively 606 (22% of the total) 21 months before, 517 (18%) 12 months before, 680 (20%) after 12 months, 560 (18%) after 21 months of EMA Warning (respectively OR 1,16 95%CI 1,10 -1,22, P 0,12 ; OR 0,76 95%CI 0,69-0,83, P 0,27 ; OR 1,01 95%CI 0,96-1,06 P 0,05). CONCLUSIONS: Our analysis clearly showed no significant differences before and after EMA warning, opening new insights in the role of the EMA warning in clinical practice.