Botulinum toxin in patients at-risk for bladder augmentation: Durable impact or kicking the can?

PURPOSE: Deferring bladder augmentation (BA) may be desirable in a pediatric neurogenic bladder (NGB) with worsening compliance, but prior studies have questioned whether onabotulinum toxin A (BTX) demonstrates durable improvement in compliance. We present our overall experience with BTX and its role in mitigating the "at-risk" NGB, as determined by urodynamic characteristics. METHODS: A retrospective single-institution review of all BTX procedures performed during January 2010 to October 2018 was conducted. Patients with <12 months follow-up after first BTX injection were excluded. Urodynamic studies (UDS) were reviewed to assign National Spina Bifida Patient Registry (NSBPR) as well as institutionally developed (LCH) risk classification groups. Patients were considered "at-risk" for BA if they had any of the following: NSBPR risk grade of intermediate or hostile; LCH risk grades indicating end-fill pressure >25 cmH2 O or detrusor sphincter dyssynergia (DSD); upper tract changes including new hydronephrosis; new or worsening vesicoureteral reflux; or other signs of a hostile urinary tract (i.e., febrile UTIs). UDS risk grades pre and post-first BTX injection were compared in this "at-risk" group, when available. RESULTS: Thirty-nine patients underwent 162 injection procedures over a median follow-up of 65 months interquartile range (IQR 49-81). Median age at first BTX was 10 years and the median number of BTX injections per patient was 4 (IQR 2-7; range 1-12) with a median time of 6 months between injections (IQR 4-10). Twenty-six patients were deemed "at-risk" at the time of first BTX injection, and of those, 16 (61.5%) proceeded to BA at a median of 36 months (IQR 22.5-42). A small number (four) had BA due to upper tract changes or worsening pressures on BTX, while nine patients (five with CKD) proceeded to BA given a lack of sufficient improvement to consider BTX a long-term viable option. Post-first BTX UDS demonstrated downgrading of risk group in 38% and 63% using NSBPR and LCH classifications, respectively. CONCLUSIONS: Encouraging improvements in the urodynamic risk group were noted in some patients. With careful counseling and follow-up, BTX may safely extend the time to BA in some "at-risk" patients.

Ultrasound Shear Wave Elastography: A Novel Method to Evaluate Bladder Pressure.

PURPOSE: Children with bladder dysfunction resulting in increased storage pressure are at risk for renal deterioration. The current gold standard for evaluation of bladder pressure is urodynamics, an invasive test requiring catheterization. We evaluated ultrasound shear wave elastography as a novel means of assessing bladder biomechanical properties associated with increased bladder pressure. MATERIALS AND METHODS: Concurrent shear wave elastography and urodynamics were performed. Ultrasound shear wave elastography images were obtained of the anterior and posterior wall when empty and at 25%, 50%, 75% and 100% expected bladder capacity, and end fill volume. Regions of interest were confirmed by a pediatric radiologist. Bladder cohorts were defined as compliant (capacity detrusor pressure less than 25 cm H2O) and noncompliant (25 cm H2O or greater). Pearson correlation coefficients and a mixed effects model evaluated the relationship between shear wave speed and detrusor pressure, compliance and normalized compliance. An unpaired t-test was used for between cohort analyses. RESULTS: In all 23 subjects mean shear wave speed of the anterior and posterior bladder walls significantly correlated with detrusor pressure throughout filling. When comparing compliant and noncompliant bladders, mean shear wave speed and detrusor shear wave speed of the anterior wall significantly increased with filling of noncompliant bladders. Shear wave speed remained at baseline levels in compliant bladders. Mean shear wave speed of the anterior wall was significantly correlated with compliance and normalized compliance. CONCLUSIONS: Ultrasound shear wave elastography bladder measurements correlate well with bladder storage pressure, and shear wave speed measurements differ between compliant and noncompliant bladders. This is the first known study to demonstrate that shear wave elastography is promising as a bedside modality for the assessment of bladder dysfunction in children.

Congenital adrenal hyperplasia: current surgical management at academic medical centers in the United States.

PURPOSE: Controversy exists on the necessity for and timing of genitoplasty in girls with congenital adrenal hyperplasia. Our knowledge of surgical preferences is limited to retrospective series from single institutions and physician surveys, which suggest a high rate of early reconstruction. We evaluated current surgical treatment for congenital adrenal hyperplasia at academic centers. MATERIALS AND METHODS: We queried the Faculty Practice Solutions Center database to identify all female patients younger than 18 years with a diagnosis of congenital adrenal hyperplasia between 2009 and 2012. Procedures were identified by CPT codes for vaginoplasty, clitoroplasty and other genital procedures. Reconstruction type, age at surgery and surgeon volume were analyzed. RESULTS: We identified 2,614 females in the database with a diagnosis of congenital adrenal hyperplasia who were seen at a total of 60 institutions. Of infants younger than 12 months between 2009 and 2011 as few as 18% proceeded to surgery within a 1 to 4-year followup. Of those referred to a pediatric urologist 46% proceeded to surgery. Of patients who underwent surgery before age 2 years clitoroplasty and vaginoplasty were performed in 73% and 89%, respectively, while 68% were treated with a combined procedure. A medium or high volume surgeon was involved in 63% of cases. CONCLUSIONS: Many patients with congenital adrenal hyperplasia in the database did not proceed to early reconstructive surgery. Of those referred to surgeons, who were possibly the most virilized patients, about half proceeded to early surgery and almost all underwent vaginoplasty as a component of surgery. About two-thirds of the procedures were performed by medium or high volume surgeons, indicative of the surgical centralization of disorders of sexual development.

Urinary diversion during and after pediatric pyeloplasty: a population based analysis of more than 2,000 patients.

PURPOSE: We evaluated the use and efficacy of intraoperative urinary diversion with ureteral stent or nephrostomy tube during pyeloplasty in children. MATERIALS AND METHODS: The Faculty Practice Solutions Center® national billing database was queried to identify all pediatric pyeloplasties performed from 2009 to 2012. Patient variables, surgical approach, use of intraoperative stent/nephrostomy tube and return for postoperative stent/nephrostomy tube or second pyeloplasty were obtained. RESULTS: A total of 2,435 children underwent open (1,792) or laparoscopic/robotic (643) pyeloplasty, with intraoperative urinary diversion rates of 45% and 83%, respectively. Comparing patients with and without an intraoperative stent/nephrostomy tube, 5.6% and 7.4%, respectively, returned to the hospital for urinary diversion. Multivariable analysis revealed no association with surgical approach, but higher surgeon volume (p <0.01) and use of an intraoperative stent/nephrostomy tube (p <0.01) were associated with decreased odds of requiring postoperative urinary diversion. Second pyeloplasty rate was 3.8% and was not associated with surgical approach or use of intraoperative stent/nephrostomy tube. CONCLUSIONS: Intraoperative stent/nephrostomy tube use and increased surgeon volume were each independently associated with a significant but small decrease in risk of postoperative stent/nephrostomy tube placement. Use of an intraoperative stent/nephrostomy tube was not associated with rate of second (redo ipsilateral or contralateral metachronous) pyeloplasty.

Surgeon, and Institution Characteristics Associated Surgical Preferences in the Pediatric KIDney Stone Care Improvement Network.

OBJECTIVE: To reveal barriers and opportunities to implement evidence for the management of pediatric kidney stone disease, we determined surgeon and institutional factors associated with preferences for the type of surgical intervention for kidney and ureteral stones. METHODS: We conducted a cross-sectional study of urologists participating in the Pediatric KIDney Stone Care Improvement Network (PKIDS) trial. Questionnaires ascertained strengths of urologists' preferences for types of surgery as well as characteristics of participating urologists and institutions. The outcome was the strength of preferences for ureteroscopy, shockwave lithotripsy, and percutaneous nephrolithotomy for four scenarios for which two alternative procedures are recommended by the AUA guidelines: (1) 2 cm kidney stone, (2) 9 mm proximal ureteral stone, (3) 1.5 cm lower pole kidney stone, (4) 1 cm nonlower pole kidney stone. Principal component analysis was performed to identify unique clusters of factors that explain surgical preferences. RESULTS: One hundred forty-eight urologists at 29 sites completed surveys. Stated preferences were highly skewed except for the choice between ureteroscopy and percutaneous nephrolithotomy for a 1.5 cm kidney stone. Shockwave lithotripsy ownership and local practice patterns most frequently associated with the strength of surgeons' preferences for the type of surgery. Principal component analysis revealed that three clusters of stone, patient, and heterogenous characteristics explained 30% of the variance in preferences. CONCLUSION: There is wide variation in the strengths of preferences for surgical interventions supported by current guidelines that are partially explained by surgeon and institutional characteristics. These results reveal opportunities to develop strategies for guidelines that consider real-world drivers of care.

Application of intraoperative structured light scanning to enable post-operative evaluation of digital and 3D-printed penile models.

BACKGROUND: Penile phenotype in hypospadias is currently assessed visually or manually (e.g., ruler, goniometer) for clinical, education, and research applications. However, these methods lack precision and accuracy across raters and cannot be reevaluated retrospectively following a surgical repair. The project aim was to evaluate the precision and reliability of penile dimensions obtained from digital and three dimensional (3D) printed models created from intraoperative (OR) structured light scans (SLS) during primary pediatric penile procedures. METHODS: Boys ages 1 month to 6 years underwent first- or single-stage penile surgery at a single institution were enrolled in this prospective study (IRB #20-000143). For each patient, immediately following placement of a stay suture under consistent manual tension, intra-operative dimension measurements with a ruler were obtained. A digital 3D model was created prior to penile repositioning using an Artec Space Spider scanner and Artec Studio 13 software. Following the case, two different raters completed 10 digital measurements of each generated model in Autodesk Fusion 360. These digital models were subsequently 3D printed and two different raters completed 10 manual dimension measurements of each 3D printed model using a ruler. A one-way random effects intraclass correlation coefficient (ICC) evaluated measures of agreement between and within raters, respectively. Analyses were conducted in R version 4.2. RESULTS: Six scans were obtained (hypospadias: 4, circumcision: 2). Intra-rater assessments showed excellent precision across repeated digital measurements; manual measurements of 3D printed models had excellent reliability for glans width and penile length but poor to good reliability for glans height. Inter-rater reliability was good to excellent for glans width (0.77-0.95) and good for penile length (0.71-0.88). However, there was poor inter-rater reliability for glans height (0-0.14). Following training regarding glans height location, there was an improvement in precision and repeatability of manual and digital measurements. CONCLUSION: Digital measurement of OR-derived 3D models resulted in excellent repeatability for each rater and improved between-rater reliability over manual measurement of 3D printed models alone, ensuring that images can be compared by various surgeons both now and in the future. SLS is promising as a novel modality to digitally generate 3D models, thereby informing phenotypic analysis for research and education. Further development of digital measurement methods to ensure consistency between raters for quantitative assessment of additional parameters and assessment of the technology within the pre-operative environment for surgical planning is planned.

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.

Abnormal social behavior in nicotinic acetylcholine receptor ß4 subunit-null mice.

INTRODUCTION: Tobacco addiction has a strong social component. Therefore, nicotinic acetylcholine receptors (nAChR) may influence social behavior. Because the ß4 nicotinic receptor subunit is important for possibly related behaviors, such as anxiety-like behavior and the effects of nicotine, we studied the social behavior of mice null for the ß4 nAChR subunit. METHODS: To measure social behavior, we used the intruder test for social memory in wild-type and littermate ß4 null mice. In addition, we used a nonsocial olfactory memory test as a control. RESULTS: In the intruder test, ß4 null mice showed social amnesia: Wild-type mice spent less time actively interacting with a younger intruder on Day 2 than on Day 1, but ß4 null mice interacted for a similar time on both days. In the nonsocial olfactory memory test, control littermates and ß4 null mice learnt the associations to a similar extent, showing that the amnesic phenotype in the intruder test is specific for social settings. CONCLUSIONS: We conclude that nAChRs that contain the ß4 subunit are important for social behaviors. As those receptors are necessary to observe several effects of nicotine including withdrawal, it is tempting to speculate that the social component of tobacco use is related to the same neuronal circuits responsible for continuing tobacco use in smokers.

Advances in 3D bioprinting for urethral tissue reconstruction.

Urethral conditions affect children and adults, increasing the risk of urinary tract infections, voiding and sexual dysfunction, and renal failure. Current tissue replacements differ from healthy urethral tissues in structural and mechanical characteristics, causing high risk of postoperative complications. 3D bioprinting can overcome these limitations through the creation of complex, layered architectures using materials with location-specific biomechanical properties. This review highlights prior research and describes the potential for these emerging technologies to address ongoing challenges in urethral tissue engineering, including biomechanical and structural mismatch, lack of individualized repair solutions, and inadequate wound healing and vascularization. In the future, the integration of 3D bioprinting technology with advanced biomaterials, computational modeling, and 3D imaging could transform personalized urethral surgical procedures.

Identifying Targets for Innovation in Amazon Reviews of Bedwetting Alarms: Thematic Analysis.

BACKGROUND: Nocturnal enuresis (NE) is a frequent diagnosis in pediatric and adolescent populations with an estimated prevalence of around 15% at the age of 6 years. NE can have a substantial impact on multiple health domains. Bedwetting alarms, which typically consist of a sensor and moisture-activated alarm, are a common treatment. OBJECTIVE: This study aimed to determine areas of satisfaction versus dissatisfaction reported by the parents and caregivers of children using current bedwetting alarms. METHODS: Using the search term "bedwetting alarms" on the Amazon marketplace, products with >300 reviews were included. For each product, the 5 reviews ranked the "most helpful" for each star category were selected for analysis. Meaning extraction method was applied to identify major themes and subthemes. A percent skew was calculated by summing the total number of mentions of each subtheme,+1 for a positive mention, 0 for a neutral mention, and -1 for a negative mention, and dividing this total by the number of reviews in which that particular subtheme was observed. Subanalyses were performed for age and gender. RESULTS: Of 136 products identified, 10 were evaluated based on the selection criteria. The main themes identified across products were long-term concerns, marketing, alarm systems, and device mechanics and features. The subthemes identified as future targets for innovation included alarm accuracy, volume variability, durability, user-friendliness, and adaptability to girls. In general, durability, alarm accuracy, and comfort were the most negatively skewed subthemes (with a negative skew of -23.6%, -20.0%, and -12.4% respectively), which are indicative of potential areas for improvement. Effectiveness was the only substantially positively skewed subtheme (16.8%). Alarm sound and device features were positively skewed for older children, whereas ease of use had a negative skew for younger children. Girls and their caretakers reported negative experiences with devices that featured cords, arm bands, and sensor pads. CONCLUSIONS: This analysis provides an innovation roadmap for future device design to improve patient and caregiver satisfaction and compliance with bedwetting alarms. Our results highlight the need for additional options in alarm sound features, as children of different ages have divergent preferences in this domain. Additionally, girls and their parents and caretakers provided more negative overall reviews regarding the range of current device features compared to boys, indicating a potential focus area for future development. The percent skew showed that subthemes were often more negatively skewed toward girls, with the ease of use being -10.7% skewed for boys versus -20.5% for girls, and comfort being -7.1% skewed for boys versus -29.4% for girls. Put together, this review highlights multiple device features that are targets for innovation to ensure translational efficacy regardless of age, gender, or specific family needs.

Identifying variability in surgical practices and instrumentation for hypospadias repair across the Western Pediatric Urology Consortium (WPUC) network.

BACKGROUND: Although hypospadias outcomes studies typically report a level or type of repair performed, these studies often lack applicability to each surgical practice due to technical variability that is not fully delineated. An example is the tubularized incised plate (TIP) urethroplasty procedure, for which modifications have been associated with significantly decreased complication rates in single center series. However, many studies fail to report specificity in techniques utilized, thereby limiting comparison between series. OBJECTIVE: With the goal of developing a surgical atlas of hypospadias repair techniques, this study examined 1) current techniques used by surgeons in our network for recording operative notes and 2) operative technical details by surgeon for two common procedures, tubularized incised plate (TIP) distal and proximal hypospadias repairs across a multi-institutional surgical network. STUDY DESIGN: A two-part study was completed. First, a survey was distributed to the network to assess surgeon volume and methods of recording hypospadias repair operative notes. Subsequently, an operative template or a representative de-identified operative note describing a TIP and/or proximal repair with urethroplasty was obtained from participating surgeons. Each was analyzed by at least two individuals for natural language that signified specified portions of the procedure. Procedural details from each note were tabulated and confirmed with each surgeon, clarifying that the recorded findings reflected their current practice techniques and instrumentation. RESULTS: Twenty-five surgeons from 12 institutions completed the survey. The number of primary distal hypospadias repairs performed per surgeon in the past year ranged from 1-10 to >50, with 40% performing 1-20. Primary proximal hypospadias repairs performed in the past year ranged from 1-30, with 60% performing 1-10. 96% of surgeons maintain operative notes within an electronic health record. Of these, 66.7% edited a template as their primary method of note entry; 76.5% of these surgeons reported that the template captures their operative techniques very or moderately well. Operative notes or templates from 16 surgeons at 10 institutions were analyzed. In 7 proximal and 14 distal repairs, parameters for chordee correction, urethroplasty suture selection and technique, tissue utilized, and catheter selection varied widely across surgeons. CONCLUSION: Wide variability in technical surgical details of categorically similar hypospadias repairs was demonstrated across a large surgical network. Surgeon-specific modifications of commonly described procedures are common, and further evaluation of short- and long-term outcomes accounting for these technical variations is needed to determine their relative influence.

Scrotal fibrous hamartoma of infancy: A case report and literature review of a rare tumor of the genitourinary tract.

Fibrous hamartoma of infancy (FHI) is a rare, benign soft tissue lesion observed in infants characterized histologically by triphasic appearance of bland fibroblastic fascicles, mature adipose tissue, and nodules of primitive myxoid mesenchyme. Preoperative and intraoperative recognition of FHI presents a significant diagnostic challenge due to nonspecific imaging findings and its histologic similarities to alternate benign and malignant entities. Management requires complete local excision and clinical follow-up to monitor for recurrence. Here, we present the diagnosis, management, and two-year follow-up of a 13-month-old boy with a scrotal FHI in addition to a comprehensive literature review of this entity.

De novo testicular tissue generation from non-testicular cell lines, biologic and synthetic scaffolds: Current findings and future translational applications.

In recent decades, reproductive science has revolutionized the options for biological parenthood for the 20-50% of infertility cases affected by male factors. However, current solutions exclude those who are infertile due to absent testicular tissue. This includes anorchic 46, XY individuals due to trauma or congenital factors and transgender men with a 46, XX genotype. There is a clinical need for methods to restore testicular function independent of pre-existing testicular tissue. This mini-review analyzes studies that have applied non-testicular cell lines to generate germline and non-germline testicular parenchymal components. While only 46, XY cell lines have been evaluated in this context to date, the potential for future application of cell lines from 46, XX individuals is also included. Additionally, the role of varied culture methods, media supplementation, and biologic and synthetic scaffolds to further support testicular parenchyma generation are critiqued. De novo testicular tissue generation in this manner will require a focus on both cellular and environmental aspects of tissue engineering. Put together, these studies highlight the future potential for expanded clinical, reproductive, and endocrine management options for individuals who are currently excluded from aspects of biologic reproduction most consistent with their gender identity and reproductive preferences.

Integrated Ultrasound With Urodynamics Illustrates Effect of Bladder Volume on Upper Tract Dilation: Should we Trust Surveillance Ultrasounds?

OBJECTIVE: To evaluate if ultrasound during urodynamics (uUS) will show that traditional ultrasound (tUS) routinely underestimates the potential magnitude of upper tract dilation (UTD). METHODS: Prospective pilot study of 10 consecutive patients ≥ 5 years of age undergoing same day uUS and tUS. Using randomized images, the study pediatric radiologist determined anterior-posterior renal pelvic diameter (APD), bladder volume, vesicoureteral reflux (VUR) and UTD grades. A single pediatric urologist determined urodynamic bladder capacity and assigned either hostile, intermediate, abnormal but safe, or normal national spina bifida patient registry classification (NSBPR). RESULTS: Bladder volume on tUS was significantly smaller than final bladder volume on uUS (180 vs 363 ml: P<.001). On average, patient reported maximum catheterized/voided volumes were also 82 ml greater than final bladder capacity on uUS. UTD was upgraded in 25% of kidneys and APD increased by 0.6 cm on uUS over that seen on tUS (P=.001). Units with VUR had greater increases in APD (1.2 P=.007 vs. 0.3 cm P=0.06). Changes in APD stratified by NSBPR revealed average increases of up to 1.3 cm. CONCLUSION: Despite instructions to the contrary, patients come for tUS with a relatively empty bladder as compared to either their urodynamic or patient-reported capacity. This translates to a significant underestimation of UTD with tUS, most notably in those with VUR. Alternatives to traditional protocols include insisting patients wait until their bladder is truly full for tUS, retrograde filling their bladder, or performing uUS. Accurate assessment of UTD severity may help guide long term management.

3D-printed phantoms to quantify accuracy and variability of goniometric and volumetric assessment of Peyronie's disease deformities.

Characterization of Peyronie's disease (PD) involves manual goniometry and penile length measurement. These techniques neglect volume loss or hourglass deformities. Inter-provider variability complicates accuracy. Using 3D-printed models, we aimed to evaluate measurement accuracy and variability and establish computational assessment workflows. Five digital phantoms were created: 13.0 cm cylinder, 13.0 cm hourglass cylinder, 15.0 cm cylinder with 40° angulation, 12.0 cm straight penis, and 12.9 cm PD penis with 68° angulation and hourglass. Lengths, volumes, and angles were determined computationally. Each phantom was 3D-printed. Ten urology providers determined lengths, angles, and volumes with measuring tape, goniometer, and volume calculator. Provider versus computational measurements were compared to determine accuracy using t-tests or Wilcoxon rank-sum tests. No significant differences were observed between manual assessment of length of penile models and designed length in penile models. Average curvature angles from providers for bent cylinder and PD phantoms were 38.3° ± 3.9° (p = 0.25) and 57.5°â€†±â€†7.2° (p = 0.006), respectively. When assessing for volume, hourglass cylinder and bent cylinder showed significant differences between designed volume and provider averages. All assessments of length, angle, and volume showed significant provider variability. Our results suggest manual measurements suffer from inaccuracy and variability. Computational workflows are useful for improved accuracy and volume assessment.

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.

A multicenter study of acute testicular torsion in the time of COVID-19.

BACKGROUND: Testicular torsion is a surgical emergency, and time to detorsion is imperative for testicular salvage. During the COVID-19 pandemic, patients may delay emergency care due to stay-at-home orders and concern of COVID-19 exposure. OBJECTIVE: To assess whether emergency presentation for testicular torsion was delayed during the COVID-19 pandemic, and whether the rate of orchiectomy increased compared to a retrospective period. STUDY DESIGN: Patients were prospectively enrolled in a multicenter study from seven institutions in the United States and Canada. Inclusion criteria were patients two months to 18 years of age with acute testicular torsion from March through July 2020. The retrospective group included patients from January 2019 through February 2020. Statistical analysis was performed using Kruskal-Wallis tests, Chi-square tests, and logistic regression. RESULTS: A total of 221 patients were included: 84 patients in the COVID-19 cohort and 137 in the retrospective cohort. Median times from symptom onset to emergency department presentation during COVID-19 compared to the retrospective period were 17.9 h (IQR 5.5-48.0) and 7.5 h (IQR 4.0-28.0) respectively (p = 0.04). In the COVID-19 cohort, 42% of patients underwent orchiectomy compared to 29% of pre-pandemic controls (p = 0.06). During COVID-19, 46% of patients endorsed delay in presentation compared to 33% in the retrospective group (p = 0.04). DISCUSSION: We found a significantly longer time from testicular torsion symptom onset to presentation during the pandemic and a higher proportion of patients reported delaying care. Strengths of the study include the number of included patients and the multicenter prospective design during the pandemic. Limitations include a retrospective pre-pandemic comparison group. CONCLUSIONS: In a large multicenter study we found a significantly longer time from testicular torsion symptom onset to presentation during the pandemic and a significantly higher proportion of patients reported delaying care. Based on the findings of this study, more patient education is needed on the management of testicular torsion during a pandemic.

Nicotinic receptors in the habenulo-interpeduncular system are necessary for nicotine withdrawal in mice.

In humans, tobacco withdrawal produces symptoms that contribute to the difficulty associated with smoking cessation. Nicotine withdrawal symptoms can also be observed in rodents. A major standing question is which nicotinic receptor subtypes and which areas of the brain are necessary for nicotine withdrawal to occur. Using knock-out mice, we previously showed that the beta4, but not the beta2 subunit of nicotinic acetylcholine receptors, is necessary for the somatic manifestations of nicotine withdrawal. Since the beta4 subunit is highly expressed in the medial habenula, we focused our studies on the medial habenula and its primary target, the interpeduncular nucleus. In particular, we studied nicotine withdrawal in mice lacking the alpha2 or the alpha5 nicotinic receptor subunits, which are highly expressed in the interpeduncular nucleus. We precipitated withdrawal by systemically injecting the nicotinic antagonist mecamylamine in mice chronically treated with nicotine. Both the alpha2 and the alpha5 null mutations abolished the somatic manifestations of nicotine withdrawal. In addition, in wild-type mice chronically treated with nicotine, mecamylamine precipitated withdrawal when microinjected into the habenula or the interpeduncular nucleus, but not into the cortex, ventral tegmental area or hippocampus. Our results demonstrate a major role for the habenulo-interpeduncular system and the nicotinic receptor subunits expressed therein, in nicotine withdrawal symptoms. Our data suggest that the efforts to develop new smoking cessation therapies should concentrate on these areas and receptor types.

Use of a Closed Diurnal Indwelling Catheter for Patients With Spinal Cord Disorders: A Pilot Study.

OBJECTIVES: To evaluate an alternative to clean intermittent catheterization (CIC) for individuals with neurogenic bladder for its effects on independence, privacy, and convenience. This prospective cohort study provides an initial assessment of quality of life, safety, and efficacy of closed diurnal indwelling catheterization (CDIC). MATERIALS AND METHODS: Individuals with spinal cord disorders using CIC were prospectively screened at multidisciplinary clinic appointments. During the 24-week intervention, a foley was placed each morning and capped between scheduled bladder drainage each 3-4 hours. After a maximum of 8 hours of CDIC use, CIC was resumed. Quality of life outcome measures (the Short Form Health Survey, King's Health Questionnaire, and Pediatric Quality of Life InventoryTM (PedsQL) questionnaires), clinic evaluations, labs, imaging, and urodynamics were obtained at specified interval visits planned after 4-, 12-, and 24 weeks of study participation and compared to baseline. RESULTS: A total of 11 subjects enrolled; 8 completed the 24-week intervention. No significant difference with CDIC was observed in the Short Form Health Survey or PedsQL summary scores as compared to baseline. For the King's Health Questionnaire, physical limitations secondary to bladder function decreased significantly from baseline to the 4-week and 12-week (P = .02) but not 24-week visits. All 8 subjects who completed the 24-week intervention requested continued use. Early discontinuation occurred in 3 male participants due to urethral trauma (1) and incontinence (2). No increase in bacteriuria, urinary tract infections, or renal anatomic changes was observed. CONCLUSION: This prospective study demonstrates that CDIC may be safe and effective for short-term use. This alternative to CIC for scheduled daytime bladder drainage for neurogenic bladder warrants further consideration.

Measurement accuracy of 3-Dimensional mapping technologies versus standard goniometry for angle assessment.

BACKGROUND: A specific aspect of the hypospadias phenotype that may contribute to long-term outcomes is the presence of ventral penile curvature and the adequacy of its surgical correction. The current gold standard to assess this angle is intraoperative goniometry of an erect penis. 3-dimensional (3D) mapping technologies may overcome the limitations of these traditional methods through their combination of digital image and geometric replication to produce consistent 3D digital forms of a physical structure. The aim of this study is to evaluate the measurement accuracy and reliability of handheld 3D mapping technologies versus standard goniometry for angle assessment in a laboratory setting. METHODS: Blocks with specified angles (10-45°) were printed using a Zortrax M200 3D printer (±0.2% accuracy). Following the completion of standardized training, blinded participants measured each block angle using a baseline digit goniometer. Additionally, complete digital models of the blocks were created using 3D mapping technologies. Structured light scanning was completed using an Artec Space Spider and Artec Studio 13. Traditional photogrammetry was completed using a Canon Eos Rebel T5i DSLR camera and Agisoft Metashape Pro. Photogrammetry with a 3D camera was completed using the VECTRA H1 and VECTRA Analysis Module. All 3D models were imported into the software Autodesk Inventor in which automated angle measurements through the central plane were obtained. Statistical analysis was performed to determine the accuracy, precision and reliability of each modality using SAS 9.4 software. The reliability of goniometry and each mapping technology was evaluated using two-way random effect models with absolute agreement. RESULTS: Six 3D printed blocks were evaluated. 5 digital models per block were created using each of the 3 mapping technologies. Inter-rater reliability of goniometry was moderate (ICC 0.76, 95% CI 0.46, 0.92), whereas all mapping technologies demonstrated excellent test-retest reliability: structured light scanning (ICC 0.99; 95% CI 0.999, 0.999); traditional photogrammetry (0.99; 0.99, 0.99); 3D camera (0.99; 0.99, 0.99). Mean angle measurements and standard error for each angle and modality are provided in the table. CONCLUSIONS: This study demonstrated excellent accuracy, precision and reliability of off-the-shelf, handheld 3D mapping technologies and moderate reliability for goniometry when applied to measurements of angulation in a laboratory setting. The described methods developed in the laboratory for optimization of angle analysis from 3D models are an important step toward reliable, reproducible phenotypic analysis of congenital genitourinary conditions in future intraoperative and database development applications.