The role of uncertainty in regulating associative change.

Rescorla (2000, 2001) interpreted his compound test results to show that both common and individual error terms regulate associative change such that the element of a conditioned compound with the greater prediction error undergoes greater associative change than the one with the smaller prediction error. However, it has recently been suggested that uncertainty, not prediction error, is the primary determinant of associative change in people (Spicer et al., 2020, 2022). The current experiments use the compound test in a continuous outcome allergist task to assess the role of uncertainty in associative change, using two different manipulations of uncertainty: outcome uncertainty (where participants are uncertain of the level of the outcome on a particular trial) and causal uncertainty (where participants are uncertain of the contribution of the cue to the level of the outcome). We replicate Rescorla's compound test results in the case of both associative gains (Experiment 1) and associative losses (Experiment 3) and then provide evidence for greater change to more uncertain cues in the case of associative gains (Experiments 2 and 4), but not associative losses (Experiments 3 and 5). We discuss the findings in terms of the notion of theory protection advanced by Spicer et al., and other ways of thinking about the compound test procedure, such as that proposed by Holmes et al. (2019). (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Multipotent bone marrow cell-seeded polymeric composites drive long-term, definitive urinary bladder tissue regeneration.

To date, there are no efficacious translational solutions for end-stage urinary bladder dysfunction. Current surgical strategies, including urinary diversion and bladder augmentation enterocystoplasty (BAE), utilize autologous intestinal segments (e.g. ileum) to increase bladder capacity to protect renal function. Considered the standard of care, BAE is fraught with numerous short- and long-term clinical complications. Previous clinical trials employing tissue engineering approaches for bladder tissue regeneration have also been unable to translate bench-top findings into clinical practice. Major obstacles still persist that need to be overcome in order to advance tissue-engineered products into the clinical arena. These include scaffold/bladder incongruencies, the acquisition and utility of appropriate cells for anatomic and physiologic tissue recapitulation, and the choice of an appropriate animal model for testing. In this study, we demonstrate that the elastomeric, bladder biomechanocompatible poly(1,8-octamethylene-citrate-co-octanol) (PRS; synthetic) scaffold coseeded with autologous bone marrow-derived mesenchymal stem cells and CD34+ hematopoietic stem/progenitor cells support robust long-term, functional bladder tissue regeneration within the context of a clinically relevant baboon bladder augmentation model simulating bladder trauma. Partially cystectomized baboons were independently augmented with either autologous ileum or stem-cell-seeded small-intestinal submucosa (SIS; a commercially available biological scaffold) or PRS grafts. Stem-cell synergism promoted functional trilayer bladder tissue regeneration, including whole-graft neurovascularization, in both cell-seeded grafts. However, PRS-augmented animals demonstrated fewer clinical complications and more advantageous tissue characterization metrics compared to ileum and SIS-augmented animals. Two-year study data demonstrate that PRS/stem-cell-seeded grafts drive bladder tissue regeneration and are a suitable alternative to BAE.

Feasibility of Enhanced Recovery After Surgery (ERAS) implementation in Pediatric Urology: Pilot-phase outcomes of a prospective, multi-center study.

INTRODUCTION/BACKGROUND: Enhanced Recovery After Surgery (ERAS) is a fundamental shift in perioperative care that has consistently demonstrated an improved outcome for a wide variety of surgeries in adults but has only limited evidence in the pediatric population. OBJECTIVE: We aimed to assess the success with and barriers to implementation of ERAS in a prospective, multi-center study on patients undergoing complex lower urinary tract reconstruction. STUDY DESIGN: Centers were directed to implement an ERAS protocol using a multidisciplinary team and quality improvement methodologies. Providers completed pre- and post-pilot surveys. An audit committee met after enrolling the first 5 patients at each center. Pilot-phase outcomes included enrollment of ≥2 patients in the first 6 months of enrollment, completion of 90 days of follow-up, identification of barriers to implementation, and protocol adherence. RESULTS: A total of 40 patients were enrolled across 8 centers. The median age at surgery was 10.3 years (IQR 6.4-12.5). Sixty five percent had a diagnosis of myelomeningocele, and 33 % had a ventriculoperitoneal shunt. A bladder augmentation was performed in 70 %, Mitrofanoff appendicovesicostomy in 52 %, Monti ileovesicostomy in 15 %, and antegrade continence enema channel in 38 %. The most commonly perceived barriers to implementation on the pre-pilot survey were "difficulty initiating and maintaining compliance with care pathway" in 51 % followed by a "lack of time, money, or clinical resources" in 36 %. The pre-pilot study experience, implementation, and pilot-phase outcomes are provided in the Table. All primary and secondary outcomes were achieved. DISCUSSION: The findings of the present study were similar to several small comparative studies with regard to the importance of a multidisciplinary team, strong leadership, and continuous audit for successful implementation of ERAS. Similar barriers were also encountered to other studies, which primarily related to a lack of administrative support, leadership, and buy-in from other services. The limitations of the present study included a relatively small heterogeneous cohort and absence of a comparative group, which will be addressed in the larger exploratory phase of the trial. The findings may also not be generaziable due to the need for sustainable processes that were unique to each center as well as an absence of adequate volume or resources at smaller centers. CONCLUSIONS: ERAS was successfully implemented for complex lower urinary tract reconstruction across 8 centers through a multidisciplinary team, structured approach based on the local context, and focus on a continuous audit.

Ureteral stent extraction strings in children: Stratifying the risk of post operative urinary tract infection.

INTRODUCTION: Ureteral stents facilitate recovery and avoid external drains in pediatric ureteral reconstruction. Extraction strings avoid the need for a secondary cystoscopy and anesthetic. Due to concerns regarding febrile UTIs in children with extraction strings, we retrospectively assessed the relative risk of UTI in children with extraction strings. OBJECTIVE: Our hypothesis was that stents with extraction strings do not increase the risk of UTI after pediatric ureteral reconstruction. METHODS: Records of all children undergoing pyeloplasty and ureteroureterostomy (UU) from 2014 to 2021 were reviewed. The incidences of UTI, fever, and hospitalization were recorded. RESULTS: 245 patients mean age 6.4 years (163M:82F) underwent pyeloplasty (n = 221) or UU (n = 24). 42% (n = 103) received prophylaxis. Of these, 15% developed UTI versus 5% of those not receiving prophylaxis (p < 0.05). 42 females had prior history of UTI, compared to 20 males (p < 0.05). 49 patients had an extraction string. Stents with extraction strings were removed on average 0.6 months post-op while others underwent cystoscopic removal on average 1.26 months post-op (p < 0.05). 9 (18.4%) required hospitalization for febrile UTI while the stent with extraction string was in place, while only 13 (6.6%) of those without extraction string did (p < 0.02). Of the 9 children with a febrile UTI in the extraction string group, 6 had history of prior UTI (46.1%), compared to only 3 (8.3%) without a prior UTI (p < 0.05). With no prior UTI, there was no difference in UTI risk between those with (3, 8.3%) and without (8, 6.4%) extraction string (p = 0.71). Females with prior UTI and extraction string were more likely to develop UTI than those with prior UTI and no extraction string (p = 0.01). There were not enough males with history of UTI to analyze alone. There were 5 (10%) stent dislodgements in the extraction string group, 2 required further intervention with cystoscopy or percutaneous drainage. DISCUSSION: Extraction strings provide the assurance of drainage while avoiding the need for a second general anesthetic procedure. There is not an increased risk of UTI with extraction string in those without prior history of UTI, but we no longer routinely leave extraction strings if there is history of UTI. CONCLUSION: Children, particularly females, with prior history of UTI have a significantly increased risk of febrile UTIs associated with the use of extraction strings. Prophylaxis does not seem to reduce this risk. Patients with no prior UTI had no higher risk of UTI with extraction string use for pyeloplasty or UU.

Removal of Intraocular Foreign Bodies Using a Modified Flute Needle.

PURPOSE: To describe the construction of a novel intraocular snare and evaluate its effectiveness in intraocular foreign body (IOFB) removal. METHOD: This is a retrospective consecutive case series. Five patients underwent pars plana vitrectomy and IOFB removal using the intraocular snare constructed from modified flute needle. RESULTS: All IOFBs were successfully engaged and removed with the snare on the first attempt. Three of the 5 cases (60%) enjoyed good visual outcome (0.4-1.0) postoperatively. No complication related to the use of the snare was encountered in this case series. CONCLUSION: Intraocular foreign body snare is simple, safe, and effective in IOFB removal.

Clinical utility and interrater reliability of video urodynamics in children with isolated fibrolipoma of filum terminale.

INTRODUCTION: Children with an isolated fibrolipoma of filum terminale (IFFT) but otherwise normal spinal cord are often evaluated with video urodynamics (VUDS). VUDS interpretation is subjective and can be difficult in young children. These patients may undergo detethering surgery if there is concern for current or future symptomatic tethered cord. OBJECTIVE: We hypothesized that VUDS in children with IFFT would have limited clinical utility regarding decision for or against detethering surgery and VUDS interpretation would have poor interrater reliability. METHODS: Patients with IFFT who underwent VUDS for from 2009 to 2021 were retrospectively reviewed to evaluate clinical utility of VUDS. 6 pediatric urologists who were blinded to patient clinical characteristics reviewed the VUDS. Gwet's first order agreement coefficient (AC1) with 95% CI was used to assess interrater reliability. RESULTS: 47 patients (24F:23M) were identified. Median age at initial evaluation was 2.8yrs (IQR:1.5-6.8). 24 (51%) patients underwent detethering surgery (Table). VUDS at initial evaluation were interpreted by treating urologist as normal in 4 (8%), reassuring for normal in 39 (81%), or concerning for abnormal in 4 (9%). Based on neurosurgery clinic and operative notes for the 47 patients, VUDS made no change in management in 37 patients (79%), prompted detethering in 3 (6%), was given as reason for observation in 7 (15%), and was normal or reassuring for normal but not documented as a reason for observation in 16 (34%) (Table). Interrater reliability for VUDS interpretation had fair agreement (AC1 = 0.27) for overall categorization of VUDS and EMG interpretation (AC1 = 0.34). Moderate agreement was seen for detrusor overactivity interpretation (AC1 = 0.54) and bladder neck appearance (AC1 = 0.46). DISCUSSION: In our cohort, 90% of patients had a normal or reassuring for normal interpretation of VUDS. VUDS interpretation affected clinical course in a minority of patients. There was fair interrater reliability for overall VUDS interpretation and therefore clinical course regarding detethering surgery could vary depending upon interpreting urologist. This fair interrater variability appeared to be related to variability in EMG, bladder neck appearance, and detrusor overactivity interpretation. CONCLUSION: VUDS affected clinical management in about 20% of our cohort and supported the choice for observation in around 50% of patients. This suggests VUDS does have clinical utility in pediatric patients with IFFT. The overall VUDS interpretation had fair interrater reliability. This suggest VUDS interpretation has limitations in determining normal versus abnormal bladder function in children with IFFT. Neurosurgeons and urologists should be aware of VUDS limitations in this patient population.

Urethral pyogenic granuloma in a pediatric patient.

Pyogenic granuloma, also known as lobular capillary hemangioma, is a benign vascular tumor rarely found in the genitourinary tract. Here, we present a case of a 6-year-old boy presenting with gross hematuria who was found to have a mass at the bladder base on ultrasound. Endoscopic resection was performed, revealing the base of the mass originating from the prostatic urethra. Pathology found pyogenic granuloma. This entity has not previously been reported to arise from the pediatric urethra and should be considered on the differential for children presenting with gross hematuria and those found to have bladder or urethral masses.

Streamlining surgical trays for common pediatric urology Procedures: A quality improvement initiative.

INTRODUCTION: Procedures involving the external genitalia are the most common pediatric urologic operations. Our group identified excess instrumentation for these cases to be a potential cause of operating room (OR) inefficiency at our large, freestanding pediatric hospital. This quality improvement (QI) initiative aimed to streamline surgical instrumentation for the most-performed pediatric urologic procedures at our hospital. MATERIAL AND METHODS: Six Sigma DMAIC methodology (Define, Measure, Analyze, Improve, Control) guided this multidisciplinary, iterative QI effort. A stakeholder team utilized data review, direct observations, and multiple in-person discussions to create a new "Groin-Penis Tray" (GPT) to replace a larger tray for the 90 most common pediatric urologic procedures. Suture preference cards and expectations about which sutures would be opened for each case were updated. The primary outcome was estimated yearly cost-avoidance due to reduced sterile processing. Additional outcomes included: instruments opened/case, % cases with complete trays, Mayo stand set-up time, and % cases with unused sutures. Balancing measures included: total median OR time and tray weights. Baseline and post-implementation measures were characterized and compared. RESULTS: A QI professional, 10 pediatric urologists, 2 pediatric urology fellows, and multiple OR and sterile processing staff members participated. The Summary Figure compares baseline and post-implementation measurements. The number of instruments opened/case decreased from 146 to 65. Annual sterile reprocessing costs decreased by >$51,000. Median Mayo stand set-up time decreased from 7.3 to 3.5 min (p < 0.001). The number of cases with complete trays increased from 7/20 (35%) to 11/20 (55%, p = 0.34). The new GPT is 2.7 kg lighter than the prior tray. Median OR time remained stable (baseline: 91 min; post-implementation: 102 min, p = 0.44). The number of cases with suture waste decreased from 78% to 0% immediately post-implementation but increased to 40% one year later. DISCUSSION: This systematic, iterative QI process spanned the course of ∼2 years, including planning, building, and updating new trays, then assessing longer-term success via the control phase. The new GPT is used for most pediatric urologic procedures at our hospital, and benefits include sterile reprocessing cost savings and ergonomics. Our team gained valuable experience related to assessing QI project scope, determining key stakeholders and roles, and strategies for sustainability that we will apply to future initiatives. CONCLUSIONS: Streamlining surgical trays for common pediatric urologic procedures at a large freestanding children's hospital using established QI methodology reduced OR cost by >$51,000/year and Mayo stand set-up times without compromising balancing measures.

Autologous regeneration of blood vessels in urinary bladder matrices provides early perfusion after transplant to the bladder.

Large animal testing and clinical trials using bioengineered bladder for augmentation have revealed that large grafts fail due to insufficient blood supply. To address this critical issue, an in vivo staged implant strategy was developed and evaluated to create autologous, vascularized bioengineered bladder tissue with potential for clinical translation. Pig bladders were used to create acellular urinary bladder matrices (UBMs), which were implanted on the rectus abdominus muscles of rats and pigs to generate cellular and vascular grafts. Rectus-regenerated bladder grafts (rrBGs) were highly cellularized and contained an abundance of CD31-positive blood vessels, which were shown to be functional by perfusion studies. Muscle patterns within grafts showed increased smooth muscle formation over time and specifically within the detrusor compartment, with no evidence of striated muscle. Large, autologous rrBGs were transplanted to the pig bladder after partial cystectomy and compared to transplantation of control UBMs at 2 weeks and 3 months post-transplant. Functional, ink-perfused blood vessels were found in the central portion of all rrBGs at 2 weeks, while UBM grafts were significantly deteriorated, contracted and lacked central cellularization and vascularization. By 3 months, rrBGs had mature smooth muscle bundles and were morphologically similar to native bladder. This staged implantation technique allows for regeneration and harvest of large bladder grafts that are morphologically similar to native tissue with functional vessels capable of inosculating with host bladder vessels to provide quick perfusion to the central area of the large graft, thereby preventing early ischemia and contraction.

Implementation and sustainability of an enhanced recovery pathway in pediatric bladder reconstruction: Flexibility, commitment, teamwork.

INTRODUCTION: Although enhanced recovery pathways (ERP) provide a safe and effective way to improve the recovery of children undergoing bladder reconstruction, ERPs have not been widely adopted in pediatric urology. We describe a quality improvement initiative and outcomes after implementing a 24-element ERP at a single, freestanding children's hospital. STUDY DESIGN: Multiple stakeholder meetings were planned and executed, initially with pediatric practitioners with ERP experience to understand potential implementation barriers then with anesthesiologists, nurses, case managers, and other ancillary staff to draft our institution-specific ERP. A standardized order set was generated to improve ERP adherence. ERP adherence audits and cyclic performance evaluations held every 6-9 months facilitated continuous pathway refinement. Patient outcomes were compared with a pre-ERP historic cohort. RESULTS: Time from initial ERP planning to first implementation was 7 months. ERP was implemented in twenty consecutive patients undergoing bladder reconstruction (median age 11.3 years, range 4.1-21.1) who were compared to twenty consecutive pre-ERP patients (median age 11.4 years, range 7.7-25.1). Median post-operative length of stay (LOS) significantly decreased from 9 days (range 2-31) pre-ERP to 4 days (range 3-29) post-ERP (p < 0.05). A median of 16 (range 12-19) of 24 institutional pathway elements were implemented for each patient. Balancing measures showed no significant increases in highest Clavien complication grade, readmission rate, or unplanned return to the operating room within 30 post-operative days. DISCUSSION: Implementation of ERP is feasible but requires commitment from multi-disciplinary stakeholders. While we were unable to consistently achieve 80% of the elements, we successfully implemented the pathway and improved our patients' recovery processes (indirectly reflected by a decreased post-operative LOS) with adherence to a median of 67% of elements. Our implementation and effectiveness results are specific to our center and may not be generalizable. However, our experience may offer some insight for others interested in ERP implementation and encourage initiation of their own institutional pathways. CONCLUSION: Successful ERP implementation at our hospital for children undergoing bladder reconstruction was facilitated by open communication, early stakeholder involvement, and monitoring ERP adherence. ERP implementation significantly decreased LOS without increasing post-operative complications and readmissions (Summary figure).

Protecting the Rescorla-Wagner (1972) theory: A reply to Spicer et al. (2020).

Rescorla (2001) used the compound test procedure to compare associative changes to cues located at different points on a performance scale. He found that associative changes to cues conditioned in compound are not necessarily equal, as predicted by common error term theories like Rescorla and Wagner (1972), but instead are larger for the poorer predictor of a trial outcome. Hence, Rescorla proposed a modification to the Rescorla-Wagner model whereby associative change is calculated as the product of 2 error terms: a common error term, as in the original model, and a unique error term for each cue present, which accounts for his findings that the poorer predictor of a trial outcome undergoes more associative change. In a recent study, Spicer, Mitchell, Wills, and Jones (2020) reported findings that appear to be inconsistent with Rescorla's proposal. These authors compared associative changes to cues that differed in associative strength as well as the certainty with which they predicted a trial outcome: One cue had greater strength than did the other, but its prediction of the trial outcome was less certain. Spicer et al. found that the cue that evoked a larger prediction error (the more certain cue) underwent less (not more) associative change and, thereby, concluded that associative change in people is not primarily determined by prediction error. Instead, they argued that cues that predict certain outcomes are somewhat protected from further associative change (theory protection), resulting in greater change to cues that predict uncertain outcomes. In this article, we offer an alternative explanation for the Spicer et al. findings using an approach described by Holmes, Chan, and Westbrook (2019). We show that if the learning-to-performance mapping function is a double sigmoid across the full range of associative strength, the Rescorla-Wagner model accommodates Rescorla's compound test results, as well as those reported by Spicer et al. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Utilization of and barriers to enhanced recovery pathway implementation in pediatric urology.

INTRODUCTION: Enhanced Recovery Pathways (ERPs), also known as ERAS® pathways, are standardized pathways composed of 21-24 perioperative elements designed to improve post-surgical recovery. ERP has been shown to be safe and effective in children undergoing bladder reconstruction but has not been widely utilized. OBJECTIVE: The aim of this study was to assess utilization of ERPs in pediatric urology and identify barriers to establishing these standardized pathways. STUDY DESIGN: Pediatric urologists who were members of the Societies for Pediatric Urology (SPU) were surveyed regarding their familiarity with standardized ERPs, current use of ERP elements, and encountered or perceived barriers to standardized ERP implementation. Willingness to implement ERP elements in a child undergoing bladder reconstruction was assessed with a 5-point Likert scale. Descriptive analysis was performed; Fisher's exact test was performed to assess associations between respondent demographics and ERP familiarity. RESULTS: Of 714 distributed surveys, 113 (16%) valid responses were collected. 69% of respondents were male, 58% practiced at academic institutions, and 57% performed 1-5 bladder reconstructions a year. 61% were somewhat familiar or not familiar with standardized ERP. While 54% currently utilize individual ERP elements, only 20% have standardized pathways. Out of 24 possible ERP elements, a median of 15 elements (range 0-24) were implemented by the respondents whether they reported they were implementing ERP elements or had standardized pathways in place. 15 of 24 ERP elements were found to be nearly universally acceptable, with greater than 90% of respondents being somewhat or very willing to implement them in the presented case scenario (Summary Figure). 62% and 56% of those who currently implement ERP elements and experienced barriers noted lack of administrative/leadership support and inability to achieve consensus among pediatric colleagues, respectively, as common barriers in standardization. For those who have not attempted standardization, the most common perceived barrier was pathway unfamiliarity (48%). DISCUSSION: Over half of respondents were not familiar with enhanced recovery pathways but were willing to implement a majority of the pathway elements, suggesting potential for ERP standardization in pediatric urology. Buy-in from colleagues and leadership would be necessary to overcome perceived barriers of standardized pathway development. CONCLUSION: Administrative support and more widespread knowledge of ERP amongst pediatric urologists are necessary to facilitate further implementation in children undergoing bladder reconstruction.

Effects of Anti-Inflammatory Nanofibers on Urethral Healing.

Protracted postsurgical inflammation leading to postoperative complications remains a persistent problem in urethral reconstruction. Nanofibers in the form of peptide amphiphiles expressing anti-inflammatory peptides (AIF-PA) have positively modulated local inflammatory responses. Urethroplasty is performed to repair 5 mm ventral urethral defects with: uncoated small intestinal submucosa (SIS); SIS dip-coated with AIF-PA1 (anti-inflammatory treatment), or SIS dip-coated with AIF-PA6 (control) on 12-week-old male Sprague Dawley rats (n = 6/group/timepoint). Animals are euthanized at 14 and 28 d postsurgery. Hematoxylin-eosin, Masson's Trichrome, and immunohistochemistry with primary antibodies against myeloperoxidase (MPO; neutrophils), CD68, CD86, CD206 (macrophages), and proinflammatory cytokines TNFα and IL-1ß are performed. Complete urethral healing occurs in 3/6 uncoated SIS (50%), 2/6 SIS+AIF-PA6 (33.3%), and 5/6 SIS+AIF-PA1 (83.3%) animals at 14 d and all at 28 d. Application of AIF-PA1 to SIS substitution urethroplasty decreases MPO+ neutrophils, CD86+ M1 proinflammatory macrophages, TNFα, and IL-1ß levels while concurrently increasing levels of CD206+ M2 proregenerative/anti-inflammatory macrophages at the anastomoses and the regenerated tissue at the wound bed (REGEN). AIF-PA1 treatment enhances the healing process, contributing to earlier, complete urethral healing, and increased angiogenesis. Further studies are needed to elucidate the specific mechanism of inflammatory response modulation on angiogenesis and overall urethral healing.

Challenging proximal hypospadias repairs: An evolution of technique for two stage repairs.

INTRODUCTION: Proximal hypospadias repair remains challenging. Our approach to the first stage of two-stage proximal hypospadias repairs has evolved from using Byars' flaps to preputial inlay grafts in anatomically suitable cases and pedicled preputial flaps in more complex repairs. We reviewed our outcomes, hypothesizing that inlay grafts and pedicled preputial flaps were associated with lower complication risks than Byars' flaps. STUDY DESIGN: A single institution, retrospective, cohort study of consecutive two-stage, primary, proximal hypospadias repairs performed from 2007 to 2017 was conducted. Patients with <6 months follow-up and incomplete operative reports were excluded. Risk of complications (fistula, dehiscence, diverticulum, meatal stenosis, stricture) were evaluated following urethroplasty and stratified by first-stage repair technique. As technique refinements have been made since 2012, comparisons between two temporal subgroups (those who underwent repair in 2007-2012 and in 2013-2017) were made. RESULTS: 78 of 127 patients met inclusion criteria. Overall complication rate was 47% (Summary Table). Median follow-up was 25.4 months (range 6.4-128.5 months) after urethroplasty. Pedicled preputial flaps (hazards ratio [HR] 0.30; 95% Confidence Interval [CI] 0.14-0.65) and inlay grafts (HR 0.32; 95% CI 0.11-0.95) were associated with lower complication risks compared to Byars' flaps (Summary Table). Median time to complication was significantly shorter for Byars' flaps (5.7 months) than for inlay grafts (40.6 months) and pedicled preputial flaps (79.2 months) by Kaplan Meier analysis. Temporal subgroup comparisons showed that overall complication rates decreased from 70% to 31% (p = 0.001), but differences in complication rates by first-stage technique were not statistically significant. DISCUSSION: In our cohort, repairs with Byars' flaps had the highest complication rate, which is consistent with our observations that urethras tubularized from Byars' flaps lack appropriate backing and are hypermobile and irregular. To overcome these shortcomings, modifications were made to our approach to two-stage proximal hypospadias repairs with the use of inlay grafts and pedicled preputial flaps quilted to the underlying corporal bodies to optimize the stability of the urethral plate. Our preliminary results are promising. CONCLUSION: Approach to the first stage of two-stage repairs affects outcomes. Pedicled preputial flaps and inlay grafts were associated with lower complication risks than Byars' flaps. Refinement of technique and patient selection may have resulted in fewer complications in the short term. However, long-term follow-up is needed.

The effects of bone marrow stem and progenitor cell seeding on urinary bladder tissue regeneration.

Complications associated with urinary bladder augmentation provide the motivation to delineate alternative bladder tissue regenerative engineering strategies. We describe the results of varying the proportion of bone marrow (BM) mesenchymal stem cells (MSCs) to CD34 + hematopoietic stem/progenitor cells (HSPCs) co-seeded onto synthetic POC [poly(1,8 octamethylene citrate)] or small intestinal submucosa (SIS) scaffolds and their contribution to bladder tissue regeneration. Human BM MSCs and CD34 + HSPCs were co-seeded onto POC or SIS scaffolds at cell ratios of 50 K CD34 + HSPCs/15 K MSCs (CD34-50/MSC15); 50 K CD34 + HSPCs/30 K MSCs (CD34-50/MSC30); 100 K CD34 + HSPCs/15 K MSCs (CD34-100/MSC15); and 100 K CD34 + HSPCs/30 K MSCs (CD34-100/MSC30), in male (M/POC; M/SIS; n = 6/cell seeded scaffold) and female (F/POC; F/SIS; n = 6/cell seeded scaffold) nude rats (n = 96 total animals). Explanted scaffold/composite augmented bladder tissue underwent quantitative morphometrics following histological staining taking into account the presence (S+) or absence (S-) of bladder stones. Urodynamic studies were also performed. Regarding regenerated tissue vascularization, an upward shift was detected for some higher seeded density groups including the CD34-100/MSC30 groups [F/POC S- CD34-100/MSC30 230.5 ± 12.4; F/POC S+ CD34-100/MSC30 245.6 ± 23.4; F/SIS S+ CD34-100/MSC30 278.1; F/SIS S- CD34-100/MSC30 187.4 ± 8.1; (vessels/mm2)]. Similarly, a potential trend toward increased levels of percent muscle (≥ 45% muscle) with higher seeding densities was observed for F/POC S- [CD34-50/MSC30 48.8 ± 2.2; CD34-100/MSC15 53.9 ± 2.8; CD34-100/MSC30 50.7 ± 1.7] and for F/SIS S- [CD34-100/MSC15 47.1 ± 1.6; CD34-100/MSC30 51.2 ± 2.3]. As a potential trend, higher MSC/CD34 + HSPCs cell seeding densities generally tended to increase levels of tissue vascularization and aided with bladder muscle growth. Data suggest that increasing cell seeding density has the potential to enhance bladder tissue regeneration in our model.

Testosterone and Estrogen Repletion in a Hypogonadal Environment Improves Post-operative Angiogenesis.

OBJECTIVE: To determine the effects of perioperative hormone supplementation on postoperative periurethral angiogenesis in the setting of hypogonadism, we analyzed the urethral tissue of castrated Sprague Dawley rats supplemented with testosterone or estrogen who underwent a urethral surgery and compared it to those that did not. MATERIALS AND METHODS: 48 Sprague-Dawley rats were divided into 4 groups: (1) non-castrate (NC) controls; (2) castrate (C) unsupplemented rats; (3) castrate rats that received testosterone (T), or (4) castrate rats that received estradiol (E). Half of each group underwent urethroplasty surgery (S) while the other half were nonsurgical controls (C). With immunohistochemistry, we measured vessel density (endothelial cell marker CD31), expression levels of androgen receptor (AR), TIE-2, and estrogen receptor GPER1. RESULTS: Periurethral vascularity was significantly increased postoperatively with both testosterone and estrogen supplementation (TC vs TS: 8.92% vs 10.80%, P<.001; EC vs ES: 7.66 vs 8.73%, P = .009) as well as in noncastrated rats (NCC vs NCS: 5.86% vs 8.19%, P<.001) whereas in the absence of hormones, CD31 expression significantly decreased after surgery (CC vs CS: 3.62% vs 2.76%, P= .003). CD31 expression was strongly correlated with AR, TIE-2, and GPER1 expression indicating a mechanistic relationship. CONCLUSION: Both testosterone and estrogen supplementation increase periurethral vascularity in castrated (hypogonadal) rats undergoing urethroplasty surgery, contrary to decreased periurethral vascularity observed in the castrated non-supplemented rats. This suggests that hormonal resupplementation benefits post-operative regeneration in rats and may provide a basis for perioperative hormone supplementation in hypogonadal men prior to urethral surgery.

Urinary Tract Infection After Robot-assisted Laparoscopic Pyeloplasty: Are Urine Cultures and Antibiotics Helpful?

OBJECTIVE: To evaluate how variations in peri-operative urine culture (UCx) and antibiotic prophylaxis utilization following robot assisted laparoscopic pyeloplasty (RALP) affect post-RALP urinary tract infection (UTI) rates in children, then use data to generate a standardized care pathway. METHODS: Patients undergoing RALP at a single institution from January 2014 to October 2018 were retrospectively reviewed. Patients with vesicoureteral reflux, neurogenic bladder, intermittent catheterization, <=2 months follow-up after stent removal, or age >=18 years were excluded. UCx use, UCx results, and pre- and post-RALP antibiotic use were recorded. The primary outcome was symptomatic UTI, tracked until 60 days after stent removal. UTI was defined as presence of fever or urinary symptoms, a positive UCx with >=10,000 colony forming units of one uropathogen, and a positive urinalysis. RESULTS: A total of 152 patients were included (72% male [73% circumcised], 61% white, and 23% Hispanic). One underwent a re-operative pyeloplasty, yielding 153 encounters. Eight patients (5.2%; 95% CI 1.7-8.7%) developed post-RALP UTI. Uncircumcised status and use of pre-operative prophylactic antibiotics were associated with post-RALP UTI (P = .03 and P < .01, respectively). Use of post-RALP antibiotics, whether prophylactic or therapeutic, was not associated with lower UTI rates (P = .92). Positive pre-RALP UCx and positive intra-operative stent removal UCx were associated with higher UTI rates (P = .03 and P < .01, respectively). CONCLUSION: UTI occurred in 5.2% of our cohort of >150 patients. As post-RALP antibiotic use was not associated with lower UTI rates, prophylactic antibiotics may be reserved for patients with risk factors. A standardized care pathway could safely reduce unnecessary utilization of UA/UCx and antibiotics.