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.

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.

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.

Role of Perilesional Sampling of Patients Undergoing Fusion Prostate Biopsies.

Recently, researchers have proposed perilesional sampling during prostate biopsies to avoid systematic biopsies of patients at risk of prostate cancer. The aim of our study is to evaluate the role of perilesional sampling to avoid systematic biopsies of patients undergoing fusion biopsies. A prospective cohort of patients undergoing transrectal MRI transrectal fusion biopsies were consecutively enrolled. All the patients underwent systematic biopsies (SB), targeted biopsies (TB) and perilesional biopsies within 10 mm from the lesion (PB). The detection rates of different strategies were determined. A total of 262 patients were enrolled. The median age of those enrolled was 70 years. The mean BMI was 27 kg/m2, and the mean and prostate volume was 52 mL. A PIRADS score ≥ 4 was recorded in 163/262 (40%) patients. Overall, the detection rates of cancer were 43.5% (114/262) and 35% (92/262) for csPCa. The use of the target + peri-target strategy resulted in a detection of 32.8% (86/262) of cancer cases and of 29% (76/262) of csPCa cases (Grade Group > 2). Using the target plus peri-target approach resulted in us missing 18/262 (7%) of the csPCa cases, avoiding the diagnosis of 8/262 (3%) of nsPCa cases. A biopsy strategy including lesional and perilesional sampling could avoid unnecessary prostate biopsies. However, the risk of missing significant cancers is present. Future studies should assess the cost-benefit relationship of different strategies.

Patients' Preferences and Expectations in Overactive Bladder: A Systematic Review.

The aim of our study is to review the current available knowledge regarding preferences and expectations of patients with overactive bladder (OAB). The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines were followed for this manuscript's preparation. Three online databases were searched: PubMed/Medline, Embase, and Scopus, while a combination of the following keywords was used: detrusor overactivity, overactive bladder, urinary incontinence, perspectives, expectations, and preferences. Overall, 1349 studies were retrieved and screened while only 10 studies appeared to be relevant for the scope of this review. Most of the studies were related to preferences about OAB medications (i.e., antimuscarinics); four of them reported patients' inclinations to alternative treatments in the case of medication therapy failure (i.e., neuromodulation, Botox). No data were found about diagnosis or other aspects of disease management (i.e., surgery, follow-up). Based on these findings, from the patient's point of view, the ideal medication should be cheap, without risk of cognitive function impairment, and able to reduce daytime urinary frequency and incontinence episodes.

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.

Ureteral stent encrustation: evaluation of available scores as predictors of a complex surgery.

BACKGROUND: Stent encrustation is an uncommon event (13%) with a significant impact in patients' management. Aim of our study was to evaluate the available grading systems for encrusted stents. METHODS: A retrospective analysis of encrusted stents was performed in four Italian centers between 2006 and 2020. Encrusted stents were classified according to four classifications: the Forgotten Encrusted Calcificated (FECal) Score, the Kidney Ureter Bladder (KUB) Score, the Visual Grading for Ureteral Encrusted Stent Classification and the Encrustation Burden Score (EBS). Classifications were evaluated to predict complex surgery defined as: long operative time (>60 min), need of more than one surgery, and need of a percutaneous approach. The scores were compared with receiver operating characteristic (ROC) analysis as predictors of complex surgery. RESULTS: Seventy-seven patients were evaluated with a median age of 62 years (65/70). Overall FECal score >2 was present in 45/77 (58%) patients, median KUB score was 9 (6/14) and severe EBS was found in 47/77 (63%) patients. Patients were managed with cyst lithotripsy in 13/77 (17%), with ureteroscopy in 58/77 (75%) and with percutaneous nephrolithotomy (PCNL) in 6/77 (8%). Overall, 6/77 (8%) patients required a second intervention to remove the encrusted stent. All classifications predicted the need of complex surgery. On ROC analysis KUB score presented a better accuracy in predicting complex surgery compared to FECal, V-GUES and encrusted burden. CONCLUSIONS: KUB score, FECal score, V-GUES score, and encrustation burden accurately predict the need of a complex surgery. KUB showed to be superior to other classifications according to our results.

Development of a Pocket Nomogram to Predict Cancer and Disease Specific Survival After Radical Cystectomy For Bladder Cancer: The CRAB Nomogram.

OBJECTIVES: To develop an easy tool to predict cancer specific (CSS) and disease-free survival (DFS) in patients with bladder cancer treated with radical cystectomy. METHODS: Data from a consecutive series of 2395 patients with primitive or progression to muscle invasive bladder cancer (MIBC) undergone to radical cystectomy and lymph nodes dissection in 5 centers were evaluated. Using Cox proportional hazards analyses, the Cancer of the bladder risk assessment (CRAB) nomogram was generated. Accuracy of the nomogram was evaluated by Harrell's C test. Internal validation of the model was performed using 200 bootstraps. RESULTS: Median age was 66 (IQR 58/73) years; 612/2395 (26%) patients presented an advanced pathological stage (≥pT3a); 478/2395 (20%) presented positive lymph nodes. Overall, 729/2395 (30%) presented local or distant recurrence with a median DFS of 42 (IQR 14/89) months. Overall, 642/2395 (27%) died of bladder cancer with a median follow up of 48 (IQR 22/92) months. On univariate Cox proportional hazards analyses, age, stage, and lymph nodes density were a significant predictor of 3 and5 years CSS and DFS. Accuracy of the CRAB nomogram was 0.73 and 0.71 respectively. CONCLUSION: CRAB nomogram can be a practical and easily applicable tool that may help urologists to classify the long-term CSS and DFS of patients treated with radical cystectomy and to predict the oncological outcome.

Ureteral wall thickness and distal ureteral density in patients with residual fragments after Ho:YAG laser semi-rigid ureterolithotripsy.

Recent data suggest that greater ureteral density distal to ureteral stones or increased ureteral wall thickness (UWT) can predict impacted stones. The aim of our study was to evaluate if patients with residual fragments present with greater ureteral density and larger UWT when compared to stone-free patients. From January onward, a consecutive series of patients undergoing semi rigid Ho:YAG laser ureterolithotripsy (ULT) for ureteral stones were enrolled. A non-contrast enhanced computed tomography (CT) scan was performed before the procedure to evaluate distal ureteral density (DUD) and wall ureteral thickness (UWT) at the site of ureteral stones. Patients with residual fragments were compared to stone-free patients using a matched-pair analysis (1:1 scenario). Cases were matched sequentially using the following criteria: age, gender, body mass index (BMI), stone length, hydronephrosis, location of stones, and mean Hounsfield unit (HU) of the stone. Overall, 160 patients were enrolled, mean age was 57.9 ± 14 years, mean BMI was 25.8 ± 4 kg/m2, mean length of the stone was 10.6 ± 4.9 mm, and mean UWT was 1.4 ± 1.6 mm. A total of 150/160 (94%) patients presented hydronephrosis; mean HU stone was 868 ± 327; mean DUD was 54 ± 17.8 HU. Ureteral distal density (51.7 vs 56.6; p = 0.535) and ureteral distal thickness (1.39 vs 1.54; p = 0.078) were similar in both groups of patients. In our study, the evaluation of distal ureteral density does not predict stone-free rate. Further studies should evaluate the role for preoperative computer tomography in predicting surgery outcome.

In Vivo and Ex Vivo Gene Electrotransfer in Ophthalmological Disorders.

The aim of this document is to present an overview of gene electrotransfer in ophthalmological disorders. In order to ensure an adequate variety of the assessed studies, several electronic databases were considered and studies published between January 1998 and December 2021 were analysed. Three investigators carried out data extraction and analysis, focusing on both technical (i.e., electrical protocol, type of electrode, plasmid) and medical (i.e., type of study, threated disease) aspects and highlighting the main differences in terms of results obtained. Moreover, the IGEA experience in the project "Transposon-based, targeted ex vivo gene therapy to treat age-related macular degeneration" (TargetAMD) was reported in the results section. No clinical trial was found on international literature and on ClinicalTrials.gov. Twelve preclinical studies were found including in vivo and ex-vivo applications. The studied showed that electrotransfer could be very efficient for plasmid DNA transfection. Many attempts such as modification of the electric field, buffers and electrodes have been made and the optimization of electric field setting seems to be very important. Using this technique, gene replacement can be designed in cases of retinal inheritance or corneal disease and a wide range of human eye diseases could, in the future, benefitfrom these gene therapy technologies.

Adverse events related to antimuscarinics and beta-3-agonist: "real-life" data from the Eudra-Vigilance Database.

BACKGROUND: Antimuscarinic (AM) and beta-3-agonist (B3A) treatment are the standard first-line pharmacological treatment used to manage overactive bladder (OAB) patients. Aim of our study was to analyze real-life data of adverse events related to AMs and B3A reported on Eudra-Vigilance (EV) Database. METHODS: EV database is the system for managing and analyzing information on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European Economic Area (EEA). We recorded the number of AEs for antimuscarinic and beta-3-agonist per category and severity until January 2021. RESULTS: Overall, 2313 AEs were reported for oxybutinin, 5129 for solifenacin, 2483 for tolterodine, 3523 for fesoterodine, 787 for trospium, 621 for propiverine and 7213 for mirabegron. Urinary retention was higher for fesoterodine (43%) and tolterodine (23%) when compared to solifenacin (10%), mirabegron (11%) and oxybutinin (4%). Cognitive disorder was uncommon for all the analyzed drugs analyzed. Regarding anticolinergic AEs: vision blurred, dry mouth and constipation were higher for AMs when compared to mirabegron. Their prevalence was higher in female patients. Mirabegron presented a higher risk of hypertension (7%) when compared to oxybutinin (2%, P<0.01), solifenacin (2%, P<0.01), tolterodine (2%, P<0.01) and fesoterodine (1%, P<0.01); the rate of hypertension was higher in females (63%) than males (29%) (P<0.01). The risk of acute urinary retention was also significantly higher (15% vs. 10%, P<0.01) in older patients (>85 years). CONCLUSIONS: Real life data is consistent with registry studies regarding the rate of AEs related to antimuscarinic and beta-3-agonist. However some differences were observed. Female patients present higher rates of AEs when compared to male patients. The risk of acute urinary retention was particularly evident in the octogenarians.

Percutaneous discectomy under CT and fluoroscopy guidance: an international multicentric study.

PURPOSE: To evaluate the technical efficacy, safety, and reproducibility of automated percutaneous lumbar discectomy (APLD) under CT and fluoroscopic guidance, for treating radiculopathy caused by lumbar disc herniation in patients impervious to conservative treatment. METHODS: A total of 77 patients with symptomatic lumbar disc herniation were treated with APLD in a prospective multicentric study performed in four centers across three countries. Magnetic resonance imaging and/or computed tomography was used to evaluate the disc herniation before and after the procedure. Only local anesthesia was used during these procedures. Clinical outcomes were measured with the visual analog scale (VAS) for pain at one and 6 months after the procedure. RESULTS: Technical success rate was 100% with a mean intervention duration of 30 min (15-45 min). No complications occurred during the procedure. Post-lumbar puncture syndrome occurred in three patients who were successfully treated with blood patches. VAS decreased from a mean of 8 before the intervention to 3 1 month after (p value = 0.001). The requirement for analgesia decreased from 100 to 27%. No statistically significant differences in outcomes were found between the centers. CONCLUSION: APLD with dual imaging guidance under local anesthesia is a safe, feasible, and reproducible technique to treat symptomatic lumbar disc herniation.

Design and Characterization of a Minimally Invasive Bipolar Electrode for Electroporation.

OBJECTIVE: To test a new bipolar electrode for electroporation consisting of a single minimally invasive needle. METHODS: A theoretical study was performed by using Comsol Multiphysics® software. The prototypes of electrode have been tested on potatoes and pigs, adopting an irreversible electroporation protocol. Different applied voltages and different geometries of bipolar electrode prototype have been evaluated. RESULTS: Simulations and pre-clinical tests have shown that the volume of ablated area is mainly influenced by applied voltage, while the diameter of the electrode had a lesser impact, making the goal of minimal-invasiveness possible. The conductive pole's length determined an increase of electroporated volume, while the insulated pole length inversely affects the electroporated volume size and shape; when the insulated pole length decreases, a more regular shape of the electric field is obtained. Moreover, the geometry of the electrode determined a different shape of the electroporated volume. A parenchymal damage in the liver of pigs due to irreversible electroporation protocol was observed. CONCLUSION: The minimally invasive bipolar electrode is able to treat an electroporated volume of about 10 mm in diameter by using a single-needle electrode. Moreover, the geometry and the electric characteristics can be selected to produce ellipsoidal ablation volumes.

Contained Herniated Lumbar Disc: CT- and Fluoroscopy-Guided Automated Percutaneous Discectomy-A Revival.

The combination of a new device and dual guidance (computed tomography [CT] and fluoroscopy) is similar to other percutaneous devices in achieving a mechanical decompression of the disc. The difference, however, is that the target of the decompression with the current technique is the herniated disc itself. The goal of this combined technique is to create a space, an "olive" around the probe, allowing a decrease in pressure inside the hernia. Percutaneous discectomy under combined CT and fluoroscopic guidance is a minimally invasive spine surgery that should be considered as an alternative to surgery in properly selected patients.

Percutaneous Facet Screw Fixation in the Treatment of Symptomatic Recurrent Lumbar Facet Joint Cyst: A New Technique.

We present a case of percutaneous treatment of symptomatic recurrent lumbar facet joint cyst resistant to all medical treatments including facet joint steroid injection. Percutaneous transfacet fixation was then performed at L4-L5 level with a cannulated screw using CT and fluoroscopy guidance. The procedure time was 30 min. Using the visual analog scale (VAS), pain decreased from 9.5, preoperatively, to 0 after the procedure. At 6-month follow-up, an asymptomatic cystic recurrence was observed, which further reduced at the 1-year follow-up. Pain remained stable (VAS at 0) during all follow-ups. CT- and fluoroscopy-guided percutaneous cyst rupture associated with facet screw fixation could be an alternative to surgery in patients suffering from a symptomatic recurrent lumbar facet joint cyst.

Stabilisation of a loosened femoral gamma nail by percutaneous cement injection (cementoplasty): a new technique.

Surgical repair of pertrochanteric and subtrochanteric fractures in the elderly is usually achieved using an endomedullary nail. Unfortunately, even today, some of the patients who undergo this intervention develop periprosthetic bone absorption over time that can lead to loosening of the prosthesis, resulting in pain, joint instability and the need for revision surgery. Surgical revision is hindered by potential complications related to patients' existing underlying medical conditions. It is often the case that these patients are weak and present comorbidities, which can lead to an absolute contraindication to surgery. An interesting alternative could be the stabilisation by percutaneous injection of cement (cementoplasty) in the periprosthetic space under CT and fluoroscopic guidance. In patients with absolute contraindication we performed percutaneous cementoplasty as treatment for femoral prosthesis loosening. Our procedure was technically a success following the end of the intervention period (follow-up: 6 months). The patient no longer experienced significant pain and showed stability of the prosthesis, as demonstrated by CT.

Percutaneous consolidation of loosened spine arthrodesis under CT and fluoroscopy guidance by radiologists: a new useful technique.

OBJECTIVE: The objective was to evaluate percutaneous computed tomography (CT) and fluoroscopy-guided injection of bone cement for consolidation of loosened posterior arthrodesis performed by radiologists. METHODS: A single-centre prospective study involving four consecutive patients (three women, one man) suffering from screw loosening (three at the vertebral level, one at the iliac wing level) after Posterior Lumbar Interbody Fusion (PLIF) treatment was done. The average age was 80 years. Surgical treatment was not indicated or not wished for by the patients. Institutional review board approval and informed consent were obtained. Percutaneous consolidation was performed by an interventional radiologist under CT and fluoroscopy guidance. The path of the trocars was made outside loosened screws bilaterally. Follow-up was assessed using the Visual Analog Scale (VAS). RESULTS: In all cases, bone cement was successfully placed around the loosened screw. The mean volume of cement that was injected was 3 ml. No cement leakage was observed. No neurological complication occurred. Using VAS, pain decreased from more than 9/10 preoperatively to less than 2/10 the day after the procedure for all patients (p < 0.05). CONCLUSION: This study suggests that loosening of spine arthrodesis could be successfully treated by percutaneous injection of bone cement under CT and fluoroscopy guidance. KEY POINTS: • PLIF is one of the surgical techniques for spinal arthrodesis. • Treatment indications are degenerative disease or instability following trauma, tumour, or infection. • Screw loosening is a frequent complication that can occur after surgery. • Percutaneous facet consolidation under dual guidance seems to be a feasible technique. • The procedure is performed under local anaesthesia using a minimally invasive approach.