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This week spans guidelines to genetics, with one thread throughout: how much of "standard practice" actually holds up once you compare it head-to-head against the alternative.

In this week's brief:

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Background: Stress urinary incontinence is common in women with neurogenic bladder, usually from intrinsic sphincter deficiency. Artificial urinary sphincter (AUS) and fascial pubovaginal sling (PVS) are both used, but had never been directly compared.

Methods: This retrospective, three-center study (2014–2023) included 35 women with neurogenic bladder undergoing AUS (n=16) or PVS (n=19). The primary outcome was Patient Global Impression of Improvement (PGI-I) at 3 months and last follow-up.

Results: AUS patients were older and had higher bladder capacity at baseline; PVS patients had more spinal cord injury and underwent more concomitant bladder reconstruction (42% vs. 0%). Perioperative complication rates were similar between groups, including major complications (12.5% vs. 10.5%). At 3 months, significantly more AUS patients reported being "very much improved" (68.8% vs. 31.6%). This difference was not statistically significant at last follow-up, though trends still favored AUS, including higher complete continence rates (50% vs. 27.8%) and fewer reoperations for recurrent incontinence (6.3% vs. 15.8%).

Discussion: This is the first head-to-head comparison of AUS and PVS in neurogenic SUI. Both procedures appear safe with comparable morbidity, but functional results trended toward AUS, possibly reflecting a study underpowered to detect smaller differences. Continence outcomes in this population are complicated by coexisting bladder dysfunction, and both procedures can alter bladder urodynamics over time, warranting long-term monitoring. Limitations include the small sample size, non-randomized design, and heterogeneity in follow-up duration and neurological diagnoses.

Conclusion: AUS and PVS are both viable options for neurogenic SUI in women, with similar perioperative morbidity. Functional outcomes may slightly favor AUS, but larger prospective studies with longer follow-up are needed.

Background: Same-day discharge (SDD) after robot-assisted radical prostatectomy (RARP) is gaining traction as ERAS protocols shorten recovery times. This meta-analysis compared SDD with standard inpatient (IP) care using only studies with internal comparison groups.

Methods: Nineteen comparative studies (11,211 SDD vs. 114,999 IP patients, 2005–2023) were pooled following PRISMA guidelines. The primary outcome was postoperative complications; secondary outcomes included readmissions, unplanned visits, continence, and satisfaction. A subgroup analysis examined single-port (SP) robotic platforms.

Results: Overall complication rates were lower with SDD (OR 0.65), including both minor and major complications, with the effect strongest at 90-day follow-up. No significant differences emerged in 30-day readmissions, 90-day unplanned visits, continence recovery, or patient satisfaction. Findings were similar in the SP subgroup. Notably, the apparent SDD advantage held in retrospective studies but disappeared in prospective ones, suggesting selection bias likely drove much of the observed benefit.

Discussion: The authors caution against interpreting lower SDD complication rates as proof that early discharge itself is protective healthier, lower-risk patients were likely preferentially chosen for SDD. Comparable readmission rates suggest SDD does not increase healthcare burden when patients are well-selected. Catheter management and structured patient preparation (including digital prehabilitation tools) appear important to SDD success.

Limitations: Evidence is mostly retrospective, from US academic centers using a single robotic platform, with inconsistent reporting of comorbidities and patient-reported outcomes.

Conclusion: Current evidence cannot establish causal superiority of SDD over inpatient care due to selection bias, but complication and readmission rates within SDD cohorts are low and clinically acceptable, supporting feasibility in carefully selected patients. Prospective studies are needed to refine selection criteria.

Background: Outcomes after radical cystectomy (RC) for pathological non–muscle-invasive bladder cancer (NMIBC) are generally good, but some patients still recur or die from disease. Reliable risk-stratification tools remain limited.

Methods: This retrospective study pooled 1032 patients with pTis/pTa/pT1, node-negative, margin-negative disease from nine centers (2000–2015), none of whom received perioperative therapy. The primary outcome was recurrence-free survival (RFS); secondary outcomes were cancer-specific survival (CSS) and overall survival (OS).

Results: Lymphovascular invasion (LVI), present in only 3.8% of patients, was the strongest independent predictor of both recurrence (more than double the risk) and cancer-specific death (over 2.5 times the risk), with 5-year RFS of 71.5% vs. 84.7% and CSS of 83.2% vs. 91.1% for LVI-positive vs. LVI-negative patients. Pathological stage alone showed no independent prognostic value. LVI's effect was concentrated in the first two postoperative years, and the excess mortality it caused was driven specifically by cancer death rather than other causes. Age was the main predictor of overall survival. Despite these significant associations, the model's overall ability to predict individual outcomes was modest (C-index ~0.59), and decision curve analysis showed no clinical benefit over a "treat none" approach at relevant risk thresholds.

Discussion: By restricting analysis to a homogeneous pathological NMIBC cohort, this study isolates LVI's prognostic impact from confounding by more advanced disease. LVI-positive pT1 patients showed outcomes approaching those seen in muscle-invasive disease, suggesting biologically aggressive behavior despite favorable staging. Because no patients received systemic therapy, the study cannot determine whether LVI-positive patients would benefit from adjuvant treatment but this subgroup may be useful for enriching future clinical trials. The modest discrimination means these findings support closer surveillance and trial selection, not individualized treatment decisions.

Limitations: Retrospective design, low LVI prevalence (limiting statistical power), institutional variability in pathological assessment, evolving cystectomy criteria over the 16-year study period, and missing data on prior intravesical treatment and recurrence patterns.

Conclusion: LVI independently identifies a small, high-risk subgroup of pathological NMIBC patients after cystectomy, while stage alone adds little prognostic value. These findings support LVI-guided surveillance and trial enrichment, though external validation and prospective study are needed before any treatment recommendations can be made.

Background: Severe (proximal) hypospadias is a rare, complex subset of this congenital anomaly, arising from intertwined genetic, hormonal, and environmental factors. This study examined how clinical, endocrine, and genetic profiles relate to one another in affected children.

Methods: This prospective study analyzed 34 male patients with severe hypospadias. Preoperative hormone levels (testosterone, dihydrotestosterone, adrenal precursors, and gonadotropins) were measured, and whole-exome sequencing was used to identify genetic variants.

Results: Clinically relevant genetic variants; pathogenic, likely pathogenic, or of uncertain significance were found in 41.2% of patients (14/34). Those carrying variants had notably more complex presentations, including significantly more associated malformations and a much higher rate of cryptorchidism, particularly in the pathogenic/likely pathogenic subgroup (71.4%, compared to 5% in patients without variants). Hormonally, androgen levels (testosterone and DHT) were broadly low across the cohort, but patients carrying genetic variants showed selectively elevated adrenal-derived precursor hormones (17α-hydroxyprogesterone and DHEA). Both 17α-OHP levels and the testosterone-to-DHT ratio correlated positively with the number of associated malformations present.

Discussion: These findings suggest severe hypospadias often reflects broader developmental and endocrine dysregulation rather than an isolated anatomical defect. The selective elevation of adrenal hormone precursors in genetically-positive patients points to possible disruption further upstream in steroid hormone synthesis, potentially involving enzymes such as CYP21A2 or CYP17A1, rather than disruption limited only to the classic 5α-reductase pathway. The strong link between pathogenic variants and multi-organ involvement (especially cryptorchidism) supports viewing severe hypospadias as part of a broader developmental syndrome in some patients, warranting screening for other congenital anomalies.

Limitations: Small sample size reflecting disease rarity, single-timepoint hormone measurements rather than dynamic testing, unconfirmed functional significance of variants of uncertain significance, and lack of long-term follow-up.

Conclusion: The combination of proximal hypospadias and cryptorchidism is a strong clinical signal for an underlying pathogenic genetic variant. The authors recommend prioritizing whole-exome sequencing in this subgroup to improve diagnostic yield and guide personalized management.

Ultrasound is widely regarded as highly accurate for diagnosing scrotal disease in adults. However, the underlying causes and presentation of acute scrotal pain in children and young people (CYP) differ meaningfully from adults, meaning adult diagnostic performance data may not translate reliably to pediatric patients. The authors note they have observed cases where clinicians applied adult-pattern confidence and interpretation to pediatric ultrasound findings, with testicular loss resulting from this mismatch.

This review aimed to critically examine the existing literature to determine the true diagnostic accuracy of ultrasound specifically for testicular torsion in children and young people, focusing on studies whose follow-up methodology could reliably detect torsion cases that were initially missed.

The authors conducted a systematic review and meta-analysis, searching PubMed, MEDLINE, Scopus, and Web of Science from each database's inception through September 2023, using a pre-registered PROSPERO protocol. Two authors independently extracted data, and study quality was assessed using the QUADAS-2 tool. The review specifically prioritized studies that used either surgical confirmation or at least 12 months of follow-up in non-operatively managed cases as the reference standard — an approach designed to catch delayed testicular atrophy that would reveal a torsion missed at initial presentation. Only studies with this kind of follow-up design were included in the formal meta-analysis.

Across 38 identified papers, a combined total of 6,790 cases were reported. Many studies had methodological weaknesses, including poorly defined outcomes and inadequate follow-up duration. When the analysis was narrowed to the 10 highest-quality studies meeting strict methodological criteria, pooled results showed a sensitivity of 0.93 and specificity of 0.99 for ultrasound in detecting testicular torsion. Doppler ultrasound performed by appropriately trained operators showed strong diagnostic performance overall. However, when the data were extrapolated particularly for cases where blood flow appeared preserved on ultrasound the analysis suggested that approximately 5.6% of torsion cases were still missed.

This review confirms that ultrasound generally performs very well as a diagnostic tool for testicular torsion in children and young people. Despite this strong overall accuracy, the finding that preserved blood flow alone was associated with a meaningful missed-torsion rate (5.6%) is clinically significant, since flow preservation is often used reassuringly to rule out torsion. The authors recommend that ultrasound be used as a supportive tool in cases where the clinical picture is genuinely ambiguous, rather than as a gatekeeping step that delays surgery. Critically, they emphasize that when torsion is clinically obvious, patients should proceed directly to surgical exploration without waiting for ultrasound confirmation, in order to avoid treatment delays that could risk testicular viability.

Urolithiasis (kidney stone disease) affects a large portion of the global population, with roughly a quarter of patients eventually needing intervention. Ureteroscopy with laser lithotripsy is a well-established, minimally invasive treatment for ureteral and renal stones, but ureteral spasm or limited dilation can sometimes hinder scope passage, increasing the need for secondary procedures and prolonging surgery. This has prompted interest in pharmacological adjuncts that relax ureteral smooth muscle to ease scope insertion.

Aminophylline, a soluble derivative of theophylline, works by inhibiting phosphodiesterase enzymes, which raises intracellular cAMP and relaxes smooth muscle. When applied locally during ureteroscopy, it may relax the ureter directly at the site of treatment while limiting systemic side effects. Although other agents like alpha-blockers and calcium channel blockers have been studied extensively for this purpose, no prior systematic review had specifically evaluated locally administered aminophylline. This review aimed to fill that gap.

The authors conducted a PRISMA-guided systematic review, registered with PROSPERO, searching multiple databases through November 2025 for randomized controlled trials comparing local aminophylline against placebo in adults undergoing ureteroscopy for stones. Three eligible trials were identified out of an initial 501 records. The primary outcome was residual stone proportion (derived from stone-free rate); secondary outcomes included operative time, need for postoperative ureteral stenting, and auxiliary procedures (such as secondary ureteroscopy or shockwave lithotripsy). Risk of bias was assessed using the Cochrane RoB-2 tool, and statistical pooling used random-effects models, with a more conservative sensitivity analysis (the Hartung–Knapp–Sidik–Jonkman, or HKSJ, correction) applied to account for the small number of included studies.

In all three trials, aminophylline (250 mg in 150 mL of saline solution) was instilled into the ureter via the ureteroscope, with surgery beginning five minutes later; control groups received saline alone.

The three trials together included 310 patients (155 receiving aminophylline, 155 receiving placebo). Patients who received local aminophylline had significantly fewer residual stone fragments (a 70% relative risk reduction) and significantly fewer auxiliary procedures (an 85% relative risk reduction), with no meaningful inconsistency between trials for either outcome. Reductions in operative time and the need for postoperative ureteral stenting were also observed in the initial analysis, but these effects lost statistical significance once the more conservative HKSJ correction was applied meaning these particular findings should be considered preliminary rather than confirmed.

Safety data were reassuring: aminophylline was generally well tolerated, with no notable increase in complications such as urinary tract infections, high blood pressure, or rapid heart rate compared to placebo. Using the GRADE framework, the overall certainty of evidence was rated low for the stone clearance and auxiliary procedure outcomes, and very low for operative time and stenting outcomes.

This is described as the first systematic synthesis specifically addressing locally administered aminophylline in ureteroscopy. The biological rationale is plausible: by relaxing ureteral smooth muscle through phosphodiesterase inhibition, aminophylline may ease scope insertion, improve visualization and irrigation, and support more complete stone fragmentation, functioning somewhat like a chemical alternative to mechanical balloon dilation, but without the associated tissue trauma. The improvements in stone clearance and reduced need for follow-up procedures likely stem from this improved access and visualization during the original procedure.

The authors note that other pharmacological adjuncts, particularly alpha-1 blockers like tamsulosin, have stronger existing evidence supporting their use in ureteroscopy. Local aminophylline represents a different mechanistic approach with the added advantage of direct topical delivery, and future head-to-head trials against these other agents would help clarify its comparative value.

The review's findings rest on a small evidence base just three trials and 310 total patients — which limits statistical precision. Only one of the three trials was double-blinded, raising the possibility of performance or detection bias in the others. All studies came from a narrow set of geographic settings (Iran, India, and Pakistan), which may limit how well the results generalize elsewhere. Definitions and measurement methods for residual stones, operative time, and other outcomes varied between trials, introducing some heterogeneity that complicates direct comparison. Details on drug concentration and administration technique were also incompletely reported in at least one trial. Because only three studies were available, formal assessment of publication bias was not possible, and the very low number of events feeding into some outcomes (like auxiliary procedures) means pooled risk estimates could be somewhat inflated by sparse data.

This exploratory meta-analysis offers preliminary, low-certainty evidence that locally administered aminophylline during ureteroscopic lithotripsy may reduce residual stone fragments and the need for additional procedures, with an acceptable safety profile and no major adverse events reported. However, apparent benefits for operative time and ureteral stenting did not hold up under more conservative statistical correction and should be viewed as hypothesis-generating rather than confirmed. Given the limited number of studies, modest sample size, and incomplete blinding in most trials, firm clinical recommendations cannot yet be made. Larger, double-blind, multicenter randomized trials with standardized outcome definitions are needed to confirm these findings, establish optimal dosing and administration technique, and compare aminophylline directly against other pharmacological adjuncts such as alpha-blockers.

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