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Summarizes conflict-of-interest guidelines for a multicenter clinical trial of treatment after coronary-artery bypass-graft surgery. Considerations in the development of policies.

Although many investigators have evaluated the technical variability of quantitative angiographic techniques used to study atherosclerosis regression in native coronary arteries, few have studied the variability inherent in repeated studies of atherosclerotic saphenous vein grafts. This study describes 2 studies performed during the course of the Post Coronary Artery Bypass Graft (CABG) Clinical Trial that were designed to assess the reproducibility of: (1) repeated angiographic views within a short time period; and (2) reproducibility of the total process of quantitative analysis of saphenous vein graft angiograms. Statistical methods are described that provide a more meaningful assessment of the impact of measurement variability in the analytic process versus the variability related to changes induced by pharmacologic interventions. One such method, the increase in standard deviation (SD) among patients (ISDP), showed that repeated angiographic views increased the variability of calculation of lesion minimal diameter by 1.5%, whereas the ISDP for repetition of the entire process of quantitative angiographic readings increased variability 6.4%. These data from the Post CABG trial reveal that technical variability is small and has negligible impact on the conclusions of the study. [ABSTRACT FROM AUTHOR]

Background: Female urethral stricture (FUS) is a rare entity that causes great morbidity and suffering in those affected. As the available scientific data is sparce, there are no formal guidelines or standard of care for this disease., Methods: This is a narrative review of the surgical management for female urethral stricture. The literature review was performed on PubMed. Articles were limited to English, but there was no limitation in terms of date., Results: Management of FUS is divided between endoscopic and open surgical repair. Urethral dilation with or without urethrectomy can be offered as a first-line treatment. However, the rate of success of this procedure remains inferior to open surgical repair, and its efficacy decreases with the number of previous dilations. For distal urethral strictures, distal urethrectomy and advancement meatoplasty may be considered. Vaginal flaps are readily available, easy to harvest, well-vascularized, and allow for a dorsal or ventral orientation urethroplasty. The results of this procedure are promising, but most studies are small and retrospective. Labia flaps are easily accessible, wet, hairless, and elastic. The main limitations with the use of vaginal or labial tissues are co-existing conditions such as lichen sclerosis or vaginal atrophy, which may affect future results. Vaginal and labial graft urethroplasty can be used when it is not possible to mobilize an adequate flap. Stricture-free rates of this technique are variable. In cases of more severe stricture, an augmentation urethroplasty using buccal mucosa graft may be necessary. The techniques used in FUS replicate those for male urethral strictures, where both ventral and dorsal approaches can be utilized., Conclusions: Although there is growing interest in the field, the optimal management of FUS remains to be determined., (© 2024 Wiley Periodicals LLC.)

Introduction: The prevalence, formal definition, and diagnostic criteria of bladder outlet obstruction in owmen have not been clearly defined., Methods: This is a literature review of the definition of BOO in women, its prevalence, as well as its differential diagnosis., Results: The main causes of BOO in women are divided into functional and anatomic conditions. Functional etiologies include detrusor external sphincter dyssynergia, dysfunctional voiding, Fowler's syndrome, and primary bladder neck obstruction. Anatomic causes can be further divided into extrinsinc and intrinsic conditions. Intrinsic etiologies include urethral stricture and urethral diverticula, whereas extrinsic causes comprise pelvic organ prolapse, post anti-incontinence surgery, and Skene's gland cyst or abscess., Conclusions: There are multiple etiologies to BOO in women, and this condition is most probably underdiagnosed, owing to a lack of consensus for a standard definition., (© 2023 Wiley Periodicals LLC.)

Urine samples of female patients with overactive bladder (OAB) are characterized by low levels of nerve growth factor (NGF) and elevated concentrations of nitric oxide (NO) compared to healthy controls. We therefore examined how NO might regulate NGF synthesis using rat bladder smooth muscle (SMCs) and urothelial (UROs) cells in culture. In UROs, incubation in hyperglycemic conditions to mimic insulin insensitivity present in the OAB cohort increased secretion of NO and concomitantly decreased NGF, except when the NO synthase inhibitor, l-NAME (1 mM) was present. Sodium nitroprusside (SNP) (300 μM, 24 h), a NO generator, decreased NGF levels and decreased cyclic GMP (cGMP) content, a process validated by the cGMP synthase inhibitor ODQ (100 μM). Alternatively, SNP increased mRNA of both NGF and matrix metalloproteinase-9 (MMP-9). MMP-9 knockout of UROs by Crispr-Cas9 potently decreased the effect of SNP on NGF, implying a dependent role of NO on MMP-9. On the other hand, matrix metalloproteinase-7 (MMP-7) activity was increased by SNP, which taken together with increase in NGF mRNA, suggests a compensatory mechanism. In SMCs, hyperglycemic conditions had the same effect on extracellular content of NO and NGF than in UROs. SNP also decreased NGF secretion but increased cGMP content. Stable permeable analogs of cGMP 8-(4-Chlorophenylthio)-cGMP (1 mM) and N2,2'-O-Dibutyryl-cGMP (3 mM) inhibited NGF release. NGF and MMP-9 mRNA expression was unchanged by SNP. Deletion of MMP-9 in SMCs by Crispr-Cas9 did not alter the effect of SNP. Finally, SNP decreased MMP-7 activity, diminishing the conversion of proNGF to NGF. These results demonstrate that enhanced NO secretion triggered by high glucose decreases NGF secretion through pathways unique for each cell type that involve cGMP and proteases MMP-7 and MMP-9. These results might help to explain our observations from the urine from patients with OAB associated with metabolic syndrome., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exist., (Copyright © 2023. Published by Elsevier Inc.)

Background: Little is known about the effect of catheterization during pressure-flow studies (PFS) on voiding efficiency in children. Our objective was to determine the effect of urethral catheterization on Qmax and flow index (FI) during PFS compared to the free flow of uroflowmetry (UF)., Methods: We retrospectively reviewed 63 consecutive children who underwent UF and PFS at our center on the same day (2019-2022). Voiding data was available for 46 patients. Patients first underwent a UF with full bladder, then PFS after urethral catheter insertion. Patients with urethral pathologies (n = 6), on clean intermittent catheterization (CIC) (n = 2) and with major comorbidities (n = 2) were excluded. Indications for UF/PFS were LUTS, recurrent UTIs, incontinence or neurosurgical pre-operative evaluation. Data was collected from the UF and the PFS and compared using paired t-test. The idealized Qmax and flow index (FI) were calculated for UF and PFS using the formulas described by Franco et al.: Male Qmax = 11.26 + 0.0701(TBC [total bladder capacity]) - 0.0000513(TBC); Female Qmax = 10.723 + 0.073(TBC) - 0.0000423(TBC), FI = Actual Qmax/Expected Qmax (Franco and et al., 2016; Franco et al., 2018; Franco and et al., 2016)., Results: Median age was 7 years old (IQR 5-11). Twenty-one (40%) patients were male and 32 (60%) patients were female. Of the 53 patients, 3 boys and 4 girls (n = 7; 13%) were unable to void with the catheter in place during PFS but able to void after its removal. Of the remaining 46 cases, the Qmax during PFS was 5 mL/s slower than the Qmax recorded on the UF without catheter, representing a decrease of 29% (12.3 vs 17.3 mL/s; p < 0.0001). The impact of urethral catheter during PFS was more important in males vs females (Qmax decreased by 7.7 vs 3.3 mL/s, or 45 vs 19%). The mean FI during PFS was 44%, which was a 30% reduction compared to the 74% FI obtained with UF (p < 0.00001). In males, the FI decreased by 37% on PFS, whereas it decreased 26% in females, similar to the Qmax decrease., Conclusions: Voiding efficiency, as assessed by Qmax and FI, is decreased during PFS compared to uroflow studies. Our data documents for the first time the impact of urethral catheterization on pediatric voiding efficiency. Abnormal flow rates and elevated PVRs should be used to guide patient management only if obtained by uroflow. Prospective validation comparing free flow with PFS studies will help characterize the impact of urethral catheter relative to bladder pathology, age, gender and catheter size used., Competing Interests: Conflicts of interest None., (Copyright © 2023 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Imbalance in the levels of neurotrophins, growth factors crucial in the development, function, and survival of neurons is commonly observed in many pathological states. Concentrations of brain-derived neurotrophic factor (BDNF) and its precursor (proBDNF) were measured in the urine of a cohort of aging female patients with overactive bladder disease (OAB). When reported to creatinine, levels were similar between OAB patients and healthy controls. However, the ratio proBDNF/BDNF was significantly decreased in the OAB group. Receiver operating characteristic (ROC) curve analysis of the ratio proBDNF/BDNF displayed a good diagnostic value for OAB (AUC = 0.729). Clinical questionnaires of symptom severity (OABSS and IIQ-7) were negatively correlated with this ratio. On the other hand, microRNAs (miRNA) involved in proBDNF gene translation were expressed at comparable levels between groups. However, urinary enzymatic activity of matrix metalloproteinase-9 (MMP-9), the enzyme that cleaves proBDNF into BDNF, was increased in OAB compared to controls. Levels of miR-491-5p, the main miRNA that downregulates MMP-9 synthesis, were greatly decreased in urine from OAB patients. These results suggest that the ratio proBDNF/BDNF could be useful in the phenotyping of OAB in an aging population, and the difference could originate from enhanced MMP-9 enzymatic activity rather than translational control.

Study Design: Economic evaluation study., Objectives: To investigate the long-term cost-effectiveness of clean intermittent catheterization (CIC) compared with suprapubic catheters (SPC) and indwelling urethral catheters (UC) among individuals with neurogenic lower urinary tract dysfunction (NLUTD) related to spinal cord injury (SCI) from a public healthcare perspective., Setting: University affiliated hospital in Montreal, Canada., Methods: A Markov model with Monte Carlo simulation was developed with a cycle length of 1 year and lifetime horizon to estimate the incremental cost per quality-adjusted life years (QALYs). Participants were assigned to treatment with either CIC or SPC or UC. Transition probabilities, efficacy data, and utility values were derived from literature and expert opinion. Costs were obtained from provincial health system and hospital data in Canadian Dollars. The primary outcome was cost per QALY. Probabilistic and one-way deterministic sensitivity analyses were performed., Results: CIC had a lifetime mean total cost of $ 29,161 for 20.91 QALYs. The model predicted that a 40-year-old person with SCI would gain an additional 1.77 QALYs and 1.72 discounted life-years gained if CIC were utilized instead of SPC at an incremental cost savings of $330. CIC confer 1.96 QALYs and 3 discounted life-years gained compared to UC with an incremental cost savings of $2496. A limitation of our analysis is the lack of direct long-term comparisons between different catheter modalities., Conclusions: CIC appears to be a dominant and more economically attractive bladder management strategy for NLUTD compared with SPC and/or UC from the public payer perspective over a lifetime horizon., (© 2023. The Author(s), under exclusive licence to International Spinal Cord Society.)

Objective: To determine whether sodium-glucose cotransporter 2 (SGLT2) inhibitors, compared with glucagon-like peptide 1 receptor agonists (GLP-1RAs) or dipeptidyl peptidase 4 (DPP-4) inhibitors, are associated with an increased risk of early bladder cancer events., Research Design and Methods: We conducted a multisite, population-based, new-user, active comparator cohort study using the U.K. Clinical Practice Research Datalink, Medicare fee-for-service, Optum's de-identifed Clinformatics Data Mart Database (CDM), and MarketScan Health databases from January 2013 through December 2020. We assembled two cohorts of adults with type 2 diabetes initiating 1) SGLT2 inhibitors or GLP-1RAs and 2) SGLT2 inhibitors or DPP-4 inhibitors. Cox proportional hazards models were fit to estimate hazard ratios (HRs) and 95% CIs of incident bladder cancer. The models were weighted using propensity score fine stratification. Site-specific HRs were pooled using random-effects models., Results: SGLT2 inhibitor (n = 453,560) and GLP-1RA (n = 375,997) users had a median follow-up ranging from 1.5 to 2.2 years. Overall, SGLT2 inhibitors were not associated with an increased risk of bladder cancer compared with GLP-1RAs (HR 0.90, 95% CI 0.81-1.00). Similarly, when compared with DPP-4 inhibitors (n = 853,186), SGLT2 inhibitors (n = 347,059) were not associated with an increased risk of bladder cancer (HR 0.99, 95% CI 0.91-1.09) over a median follow-up ranging from 1.6 to 2.6 years. Results were consistent across sensitivity analyses., Conclusions: Contrary to previous randomized controlled trials, these findings indicate that the use of SGLT2 inhibitors is not associated with an increased risk of bladder cancer compared with GLP-1RAs or DPP-4 inhibitors. This should provide reassurance on the short-term effects of SGLT2 inhibitors on bladder cancer incidence., (© 2022 by the American Diabetes Association.)