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Nicol Corbin Bush, Warren Snodgrass The Hypospadias Specialty Center, The Colony, TX, USACorrespondence: Nicol Corbin Bush, Email bush@hypospadias.comPurpose: The few available reports regarding adults living with distal hypospadias give disparate views of the functional and aesthetic impact of this penile birth defect when it is not corrected. We reviewed symptoms and findings in consecutive men with unrepaired distal hypospadias and report those observations.Material and Methods: Men with uncorrected hypospadias were queried regarding urinary symptoms, sexual dysfunction, and aesthetic concerns. Glans fusion around the meatus was measured. Penile curvature was confirmed by photographs of erections, and its degree objectively measured in those undergoing surgery.Results: There were 51 men with a mean age of 42 years (18– 63). None had glans fusion around the meatus, and the main symptom was urine spraying in 81%. Penile curvature was present in 33%. Painful sexual activity was reported by 34% due to penile curvature, exposed urethral mucosa, or a scrotal web. All but one man experienced functional problems. In addition, 60% were bothered by their abnormal appearance.Conclusion: All but one of these men with uncorrected distal hypospadias had penile dysfunction, and 60% were additionally concerned about the atypical appearance of their penis. These results offer a different perspective than earlier reports which said that most men with uncorrected distal hypospadias were not bothered by their condition, and many were not aware of it.Keywords: adult hypospadias, uncorrected hypospadias, urine spraying, sexual dysfunction

Most urinary tract infections in women are effectively treated with a short course of antimicrobial therapy. However, a number of patients-particularly those with recurrent, persistent, or complicated infections--present more challenging diagnostic and treatment situations. The authors offer a practical approach to managing both straightforward and complex cases based on a simple clinical classification system. [ABSTRACT FROM AUTHOR]

We investigated the relationships between ceramide species concentrations in liver, plasma and very low-density lipoproteins (VLDL) particles of humans with obesity as well as the relationships between hepatic fat content and hepatic ceramide concentrations and proportional distribution. Twenty-five obese (body mass index >35 kg/m 2 ) adults participated in this study. Plasma, VLDL and hepatocellular ceramide concentrations were measured by liquid chromatography/tandem mass spectrometry. The proportionate distribution of measured ceramide species differed between liver, whole plasma and the VLDL fraction. We found significant, positive correlations between the proportion of C14:0, C18:0, C20:0 and C24:1 ceramide in the liver and whole plasma (γ = 0.491, p = 0.013; γ = 0.573, p = 0.003; γ = 0.479, p = 0.015; γ = 0.716, p = 0.00006; respectively). In contrast, only the proportional contribution of C24:1 ceramide correlated positively between VLDL and liver (γ = 0.425, p = 0.013). The percent hepatic fat correlated positively with the proportion of C18:1, C18:0 and C20:0 hepatic ceramides (γ = 0.415, p = 0.039; γ = 0.426, p = 0.034; γ = 0.612, p = 0.001; respectively), but not with total hepatic ceramide concentration. The proportions of whole plasma ceramide subspecies, especially C14:0, C18:0, C20:0 and C24:1chain length, are reflective of those of hepatic ceramide subspecies in obese humans; these appear to be markers of hepatic ceramide species composition., (© 2023 AOCS.)

Objective: This study tested whether substrate concentrations or fatty acid storage proteins predict storage of endogenous lipids in visceral adipose tissue (VAT) and upper body subcutaneous adipose tissue (UBSQ) fat., Methods: The day prior to surgery, 25 patients undergoing bariatric procedures received an infusion of autologous [1- 14 C]triolein-labeled very low-density lipoprotein (VLDL) particles, and during surgery, they received a continuous [U- 13 C]palmitate infusion/bolus [9,10- 3 H]palmitate tracer. VAT and UBSQ fat were collected to measure VLDL-triglyceride (TG) storage, direct free fatty acid (FFA) storage rates, CD36 content, lipoprotein lipase (LPL), acyl-CoA synthetase, diacylglycerol acetyl-transferase, and glycerol-3-phosphate acyltransferase activities., Results: Storage of VLDL-TG and FFA-palmitate in UBSQ and VAT was not different. Plasma palmitate concentrations correlated with palmitate storage rates in UBSQ and VAT (r = 0.46, P = 0.02 and r = 0.46, P = 0.02, respectively). In VAT, VLDL-TG storage was correlated with VLDL concentrations (r = 0.53, P < 0.009) and LPL (r = 0.42, P < 0.05). In UBSQ, VLDL-TG storage was correlated with LPL (r = 0.42, P < 0.05). CD36, acyl-CoA synthetase, glycerol-3-phosphate acyltransferase, and diacylglycerol acetyl-transferase were not correlated with VLDL-TG or palmitate storage., Conclusions: Adipose storage of VLDL-TG is predicted by VLDL-TG concentrations and LPL; FFA concentrations predict direct adipose tissue FFA storage rates., (© 2021 The Obesity Society.)

Background: Race differences in body composition and fat distribution may in part explain the differences in insulin sensitivity and the disproportionate burden of type 2 diabetes in African Americans., Objective: To determine if differences in body composition and fat distribution explain race differences in insulin sensitivity and identify obesity measures that were independently associated with insulin sensitivity., Methods: Participants were 113 lean, overweight, and obese African-American and Caucasian-American adults without diabetes. Skeletal muscle insulin sensitivity was determined using a hyperinsulinemic-euglycemic clamp (SIClamp, insulin rate:120 mU/m2/min). Subcutaneous abdominal adipose tissue (SAAT), intra-abdominal adipose tissue (IAAT), and liver fat were measured by MRI; leg fat, total fat, and lean mass were measured by DXA., Results: Race-by-adiposity interactions were significant in cross-sectional analyses utilizing multiple linear regression models for SIClamp (P < 0.05); higher BMI, fat mass, SAAT, leg fat, and liver fat were associated with lower SIClamp in Caucasian Americans but not African Americans. Race-by-IAAT interaction was not significant (P = 0.65). A central fat distribution (SAAT adjusted for leg fat) was associated with lower SIClamp in African Americans (β = -0.45, SE = 0.11, P < 0.001) but not Caucasian Americans (β = -0.42, SE = 0.30, P = 0.17). A peripheral fat distribution (leg fat adjusted for IAAT/SAAT) was associated with a higher SIClamp in African Americans (β = 0.11, SE = 0.05, P = 0.02) but lower SIClamp in Caucasian Americans (β = -0.28, SE = 0.14, P = 0.049). Lean mass was inversely associated with SIClamp in African Americans (β = -0.05, SE = 0.03, P = 0.04) but not Caucasian Americans (β = 0.08, SE = 0.05, P = 0.10) in the model for leg fat., Conclusions: Measures of overall adiposity were more strongly associated with SIClamp in Caucasian Americans, whereas body fat distribution and lean mass showed stronger correlations with SIClamp in African Americans. Insulin sensitivity may have a genetic basis in African Americans that is reflected in the pattern of body fat distribution. These findings suggest a race-specific pathophysiology of insulin resistance, which has implications for the prevention of diabetes and related cardiometabolic diseases., (Copyright © The Author(s) 2019.)

Palmitoleic acid has been classified as an insulin-sensitizing lipokine, but evidence for this from human studies has been inconsistent. We hypothesized that this is related to either the types of samples or conditions under which samples are collected. We measured plasma palmitoleic acid and total free fatty acids (FFA) using ultra-performance liquid chromatography in blood samples collected from 34 adults under a variety of conditions. We collected duplicate samples of adipose (n = 10), FFA (n = 9), and very low density lipoprotein triacylglycerol (VLDL-TAG) (n = 7) to measure the palmitoleic acid as a percentage of total fatty acids. We tested whether the percentage of palmitoleic acid was correlated with insulin resistance, as measured by homeostatic model of insulin resistance (HOMA-IR). Adipose stearoyl-coenzyme A desaturase 1 (SCD-1) protein was measured by capillary Western blotting. FFA-palmitoleic acid percentage increased as a function of total FFA and was greater (p < 0.005) in females than males. Adipose palmitoleic acid percentage was greater in females than males (p < 0.001), as was adipose SCD-1. Palmitoleic acid was greater in femoral fat than in abdominal fat in both females and males (p < 0.001), and correlated positively with HOMA-IR only in females. The test-retest reliability values for percentage palmitoleic acid were 7 ± 10% for adipose, 24 ± 26% for VLDL, and 53 ± 31% for FFA. Because FFA-palmitoleic acid percentage varies as a function of total FFA, investigators should re-evaluate how palmitoleic acid data is presented. The positive relationship between adipose palmitoleic acid and HOMA-IR in females suggests that it is not a potent insulin-sensitizing lipokine in humans., (© 2020 AOCS.)

Objective: Nonalcoholic fatty liver disease can lead to hepatic inflammation/damage. Understanding the physiological mechanisms that contribute to excess hepatic lipid accumulation may help identify effective treatments., Design: We recruited 25 nondiabetic patients with severe obesity scheduled for bariatric surgery. To evaluate liver export of triglyceride fatty acids, we measured very-low-density lipoprotein (VLDL)-triglyceride secretion rates the day prior to surgery using an infusion of autologous [1-14C]triolein-labeled VLDL particles. Ketone body response to fasting and intrahepatic long-chain acylcarnitine concentrations were used as indices of hepatic fatty acid oxidation. We measured intraoperative hepatic uptake rates of plasma free fatty acids using a continuous infusion of [U-13C]palmitate, combined with a bolus dose of [9,10-3H]palmitate and carefully timed liver biopsies. Total intrahepatic lipids were measured in liver biopsy samples to determine fatty liver status. The hepatic concentrations and enrichment from [U-13C]palmitate in diacylglycerols, sphingolipids, and acyl-carnitines were measured using liquid chromatography/tandem mass spectrometry., Results: Among study participants with fatty liver disease, intrahepatic lipid was negatively correlated with VLDL-triglyceride secretion rates (r = -0.92, P = 0.01) but unrelated to hepatic free fatty acid uptake or indices of hepatic fatty acid oxidation. VLDL-triglyceride secretion rates were positively correlated with hepatic concentrations of saturated diacylglycerol (r = 0.46, P = 0.02) and sphingosine-1-phosphate (r = 0.44, P = 0.03)., Conclusion: We conclude that in nondiabetic humans with severe obesity, excess intrahepatic lipid is associated with limited export of triglyceride in VLDL particles rather than increased uptake of systemic free fatty acids., (Copyright © 2019 Endocrine Society.)

Context: Insulin-like peptide 3 (INSL3), a protein hormone produced by Leydig cells, may play a crucial role in testicular descent as male INSL3 knockout mice have bilateral cryptorchidism. Previous studies have measured human fetal INSL3 levels in amniotic fluid only. Objective: To measure INSL3 serum levels and mRNA in fetal umbilical cord blood and fetal testes, respectively. Design: INSL3 concentrations were assayed on 50 μl of serum from male human fetal umbilical cord blood by a non-commercial highly sensitive and specific radioimmunoassay. For secondary confirmation, quantitative real-time PCR was used to measure INSL3 relative mRNA expression in 7 age-matched human fetal testes. Setting: UT Southwestern Medical Center, Dallas, TX and Medical University of South Carolina, Charleston, SC. Patients or other Participants: Twelve human male umbilical cord blood samples and 7 human male testes were obtained from fetuses 14-21 weeks gestation. Male sex was verified by leukocyte genomic DNA SRY PCR. Interventions: None. Main Outcome Measures: Human male fetal INSL3 cord blood serum concentrations and testicular relative mRNA expression. Results: INSL3 serum concentrations during human male gestational weeks 15-20 were 2-4 times higher than published prepubertal male levels and were 5-100 times higher than previous reports of INSL3 concentrations obtained from amniotic fluid. Testicular fetal INSL3 mRNA relative expression was low from weeks 14-16, rose significantly weeks 17 and 18, and returned to low levels at week 21. Conclusions: These findings further support the role of INSL3 in human testicular descent and could prove relevant in uncovering the pathophysiology of cryptorchidism., (Copyright © 2019 Harrison, Bush, Wang, Mucher, Lorenzo, Grimsby, Schlomer, Büllesbach and Baker.)

Purpose: Persistent or recurrent ventral curvature (VC) in patients with complications after proximal hypospadias repair is reported., Methods: Records of patients undergoing re-operation for complications after proximal repair performed elsewhere were reviewed, including earlier operative reports when available. Original extent of VC, means used for straightening, and presenting complaints and findings at re-operation were tabulated. Ventral curvature at re-operation was objectively measured by goniometry and classified as due to short ventral skin and/or scarring of skin/dartos, short neourethra, or short ventral corpora (corporal disproportion). The finding of corporal disproportion at re-operation was considered to be failure of initial straightening., Results: There were 73 patients with an average of 2.7 [1-5] prior operations for proximal shaft to perineal hypospadias; of which, 83% had VC at re-operation averaging 50° (30-90). This was due to short skin/scarring in 7% patients, a short neourethra in 23%, and corporal disproportion in 70%. Initial straightening was performed by chordee excision in 18 patients, dorsal plication in 23, and ventral lengthening in 15. Persistent or recurrent corporal disproportion was significantly more likely after chordee excision or dorsal plication than after ventral lengthening (p = 0.005). Of patients with VC, 93% also had urethroplasty complications, including recurrent fistulas and wound dehiscences that appeared related to the curvature., Discussion: The VC that was encountered during proximal hypospadias re-operations was important for several reasons. First, all patients with VC who had completed urethroplasty had complications that included recurrent fistulas and wound dehiscences (Figure). Even if they had healed without complications, this VC exceeded 30° in all cases, which is associated with sexual dysfunction in adults. This VC was not reported by 37% of caregivers and sometimes not apparent on pre-operative physical examination. It is possible there is selection bias in this series, although nearly all patients were self-referred for complications, and nearly 40% of them were not aware their son had VC. Furthermore, the finding that most initially had dorsal plication agrees with an earlier survey of pediatric urologists' preferences for straightening penile curvature., Conclusions: The most common complication in this series was persistent or recurrent VC, and nearly all these patients also had urethroplasty complications. This VC was more likely when the urethral plate was preserved during straightening and when chordee excision or dorsal plication rather than ventral lengthening was performed. These data suggest that surgeons should objectively measure VC and consider ventral lengthening rather than chordee excision or dorsal plication when it is ≥ 30°. Re-operations for urethroplasty complications should include artificial erection., (Copyright © 2019 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: The ability to oxidize fat is associated with a lower risk of chronic metabolic disease. Preclinical data in mice showed that a high-fat "breakfast" increased 24-h fat oxidation relative to a high-carbohydrate breakfast., Objectives: The objectives of this study were to determine whether the timing of macronutrient intake in humans affects daily fuel utilization and to examine associations between fuel utilization and metabolic indexes., Methods: Participants were 29 healthy sedentary men and women (aged 55-75 y) with a body mass index (kg/m2) between 25 and 35. Participants were randomly assigned to receive either a high-fat breakfast (FB; 35% carbohydrate, 20% protein, 45% fat; n = 13) or a high-carbohydrate breakfast (CB; 60% carbohydrate, 20% protein, 20% fat; n = 16) for 4 wk while consuming a "neutral" lunch and dinner. Twenty-four-hour and postprandial respiratory quotients (RQs) were measured by whole-room indirect calorimetry. Insulin and glucose measures including insulin sensitivity were determined by an oral-glucose-tolerance test. Measures were taken at baseline and after the 4-wk intervention. Group-by-time interactions were determined by 2-factor repeated-measures mixed-model ANOVA. Pearson's correlation analyses were used to determine associations of 24-h RQs with metabolic measures after the intervention., Results: There was a significant group-by-time interaction for change in the 24-h RQ [FB (mean ± SD): 0.88 ± 0.02 to 0.86 ± 0.02; CB: 0.88 ± 0.02 for both; P < 0.05], breakfast RQ (FB: 0.88 ± 0.03 to 0.86 ± 0.03; CB: 0.89 ± 0.02 to 0.90 ± 0.02; P < 0.01), and lunch RQ (FB: 0.089 ± 0.03 to 0.85 ± 0.03; CB: 0.89 ± 0.03 for both; P < 0.01). In the CB group at follow-up, 24-h RQ was positively associated with fasting glucose (r = 0.66, P < 0.05), glucose area under the curve (AUC) (r = 0.51, P < 0.05), and insulin AUC (r = 0.52, P < 0.05) and inversely associated with insulin sensitivity (r = -0.51, P < 0.05)., Conclusions: The macronutrient composition of breakfast affects substrate utilization throughout the day in older adults. The consumption of a high-fat, lower-carbohydrate breakfast may reduce the risk of metabolic disease. This trial was registered at www.clinicaltrials.gov as NCT03164200.

Introduction: Two reports have found that urethral plate (UP) widths <8 mm before tubularized incised plate (TIP) incision increased urethroplasty complications. The present study measured pre-incision UP width in consecutive boys undergoing TIP to determine if it affected outcomes., Methods: The present study followed the method previously used by Holland and Smith, and Sarhan et al. to measure UP width before creating glans wings or performing midline plate incision in consecutive patients with primary hypospadias and ventral curvature <30°, who all underwent TIP repair (Summary Fig.). Glans width at its widest point was also measured. Multiple logistic regression assessed urethroplasty complications (fistula, glans dehiscence, meatal stenosis/urethral stricture, diverticulum) based on pre-incision UP width, glans width, patient age, and meatal location., Results: The UP widths were determined in 224 consecutive primary TIP repairs during 2012-2015: 200 distal, 11 midshaft, and 13 proximal. The UP width was <8 mm in 192/224 (86%) patients. Mean pre-incision width was 6.1 mm (SD 1.5, range 2-11), without difference in UP widths according to meatal location (P = 0.06). Mean post-incision UP width was 12 mm (SD 2.2, range 10-16). Mean change in width after incision (delta/original UP width) was 116% (SD 63, range 20-250). There was follow-up in 186 patients for a mean of 6 months. Urethroplasty complications (five fistulas, six glans dehiscence) were diagnosed in 11 (6%): 9/165 distal, 1/9 midshaft, and 1/12 proximal repairs. There was no difference in those <8 vs ≥8 mm (11/160 vs 0/26, P = 0.17). Similarly, UP width was not different between patients with and without urethroplasty complications. Multiple logistic regression in these 186 patients - including meatal location, UP width, glans width, and age - found only glans width <14 mm was associated with increased odds of urethroplasty complications (OR 19.2, 95% CI 3.5-106, AUC = 0.799)., Discussion: The data show that pre-incision UP width is not an independent risk factor for urethroplasty complications. However, it is possible that technical factors, such as how deeply the dorsal incision is made or size of the urethral stent, might contribute to this finding by other authors. After watching the TIP repair, Smith stated that the plate incision was deeper than he made. Sarhan et al. reported a mean change of 57% in UP width after incision, whereas the present one was double at 116% (i.e. from 6 mm pre-incision to 12 mm post incision), and they used an 8-Fr catheter. While they stated that they incised the plate deeply, the lower percentage increase in width suggests that it was not as deep as was recommended., Conclusions: The UP width before incision did not increase urethroplasty complications. Surgeons do not need to measure or categorize the UP to determine suitability for TIP repair, as long as the plate incision is made deeply to the corpora., (Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Context: Although the long-term effects of testosterone on adipose tissue lipid metabolism in men have been defined, the short-term regulation of these effects is not well understood., Objective: We examined the effects of acute testosterone withdrawal on subcutaneous abdominal and femoral adipose tissue fatty acid (FA) storage and cellular mechanisms., Design: This was a prospective, randomized trial., Setting: Mayo Clinic Clinical Research Unit., Patients or Participants: Thirty-two male volunteers ages 18 to 50 participated in these studies., Interventions: Volunteers were randomized to receive (1) no treatment (control), (2) injections (7.5 mg) of Lupron®, or (3) Lupron and testosterone (L+T) replacement for 49 days, resulting in 4 weeks of sex steroid suppression in the Lupron group., Main Outcome Measures: We measured body composition, fat cell size, adipose tissue meal FA and direct free FA storage, lipoprotein lipase (LPL), acyl coenzyme A synthetase (ACS), diacylglycerol acyltransferase activities, and CD36 content., Results: Compared with control and L+T groups, acute testosterone deficiency resulted in greater femoral adipose tissue meal FA storage rates, fasting and fed LPL activity, and ACS activity., Conclusions: These results suggest that in men, testosterone plays a tonic role in restraining FA storage in femoral adipose tissue via suppression of LPL and ACS activities. FA storage mechanisms in men appear sensitive to short-term changes in testosterone concentrations., (Copyright © 2017 Endocrine Society)

Purpose: The primary aim of this report was to compare urethroplasty complications for primary distal and proximal repairs with those after 1, 2, 3, and 4 or more re-operations., Methods: Prospectively collected data on consecutive hypospadias repairs (tubularized incised plate (TIP), inlay, two-stage graft) from 2000 to 2015 were reviewed. Isolated fistula closures were excluded. Extracted information included patient age, meatal location, repair type, primary vs. re-operative surgery, number of prior operations, any testosterone use, glans width, and urethroplasty complications. Pre-operative testosterone stimulation was used during the study period until 2012. Initially, it was given for a subjectively small-appearing glans, but from 2008 to 2012 use was determined by glans width <14 mm. Patients initially managed elsewhere were queried for any testosterone treatment. The number of prior operations was determined by patient history and confirmed by review of records. Calibrations, dilations, cystoscopies, and/or isolated skin revisions were not considered as prior urethroplasty operations. Multiple logistic regression was performed for all patients, and for the subset of patients undergoing re-operation, using stepwise regression for the following potential risk factors: meatal location (distal vs. midshaft/proximal), number of prior surgeries (0, 1, 2, 3, ≥4), pre-operative testosterone use (yes/no), small glans (<14 vs. ≥14), surgery type (TIP, inlay and two-stage graft), and age (continuous in months), with P-values <0.05 considered statistically significant., Results: In contrast to the 135/1085 (12%) complication rate in patients undergoing primary distal and proximal TIP repair, re-operative urethroplasty complications occurred in 61/191 (32%) TIP, 16/46 (35%) inlay, and 49/124 (40%) two-stage repairs, P<0.0001. Data regarding testosterone use was available for 1490 (96%) patients. A total of 139 received therapy, of which 65 (46%) had urethroplasty complications vs. 229 of 1351 (16%) without treatment, P = 0.0001. Logistic regression in 1536 patients demonstrated that each prior surgery increased the odds of subsequent urethroplasty complications 1.5-fold (OR 1.51, 95% CI 1.25-1.83), along with small glans <14 mm (OR 2.40, 95% CI 1.48-3.87), mid/proximal meatal location (OR 2.54, 95% CI 1.65-3.92), and use of pre-operative testosterone (OR 2.57, 95% CI 1.53-4.31); age and surgery type did not increase odds (AUC = 0.739)., Discussion: Urethroplasty complications doubled in people undergoing a second hypospadias urethroplasty compared with those undergoing primary repair. This risk increased to 40% with three or more re-operations. Logistic regression demonstrates that each surgery increases the odds for additional complications 1.5-fold. Mid/proximal meatal location, small glans <14 mm, and use of pre-operative testosterone also significantly increase odds for complications. These observations support the theory that previously operated tissues have less robust vascularity than assumed in a primary repair, and suggest additional adjunctive therapies are needed to improve wound healing in re-operations. The finding that even a single re-operative urethroplasty has twice the risk for additional complications vs. a primary repair emphasizes the need for hypospadias surgeons to 'get it right the first time'. The fact that 40% of the re-operative urethroplasties in this series followed distal repairs emphasizes that there is no 'minor' hypospadias., Conclusions: A single re-operative hypospadias urethroplasty has twice the risk for additional complications vs. the primary repair, which increases to 40% with three or more re-operations. These results support a theory that vascularity of penile tissues decreases with successive operations, and suggest the need for treatments to improve vascularity. The higher risk for complications during re-operative urethroplasties also emphasizes the need to get the initial repair correct., (Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: We review outcomes after management of meatal balanitis xerotica obliterans (BXO). The primary outcome was recurrent meatal BXO., Methods: A database comprising mostly hypospadias patients was queried for meatal BXO. The disease was confirmed histologically in all cases. Management included topical steroids and/or immunosuppressants, and/or surgical excision of BXO with two-stage oral mucosa graft circumferential replacement urethroplasty., Results: A total of 12 patients had meatal BXO (8 boys and 4 adults). Of these, 10 had hypospadias, two presenting without prior surgery and eight returning 5-30 years after one or multiple (n = 2) repairs. Another two boys did not have hypospadias: one developing BXO 10 years after newborn circumcision and the other having persistent meatal BXO following therapeutic circumcision. Topical and intraluminal steroids (1% betamethasone or clobetasol) and tacrolimus were used for ≥12 weeks each as primary therapy or for meatal recurrence in a total of six cases. Complete response with resolution of white discoloration and relief of stranguria only occurred in two of the three receiving clobetasol, with follow up ≤12 weeks. BXO excision and urethroplasty was done in 11 patients, 10 using oral mucosa grafts; one with a focal lesion and a negative frozen section had reoperative TIP. Of the 10 undergoing excision with two-stage replacement urethroplasty, six remain disease free at a mean follow-up of 23 months (8-48 months), and four had recurrent stranguria and visible meatal BXO at a median of 26 months (22-105 months). Three of the four with recurrences had additional treatment and one was lost to follow-up. All initially had topical steroids, and two also used tacrolimus, without clinical resolution. These three then underwent a second BXO excision and two-stage oral graft replacement urethroplasty. In two recurrences, BXO was found invading from the meatus proximally within oral mucosa (Figure). Of these three with secondary urethroplasties, two are free of disease at 6 and 18 months, and the third had another meatal recurrence 6 months after the second stage., Discussion: We found topical steroids and immunosuppressants to have limited efficacy, with two clinical complete responses achieved only with clobetasol in patients with short follow-up. Forty percent of patients recurred at 2-9 years after visually complete BXO excision and two-stage oral mucosa graft replacement urethroplasty, and in two cases disease invaded into oral mucosa, the first well-documented cases of this occurrence., (Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Strictures of the neourethra after hypospadias surgery are more common after skin flap repairs than urethral plate or neo-plate tubularizations. The diagnosis of stricture after hypospadias repair is suspected based on symptoms of stranguria, urinary retention, and/or urinary tract infection. It is confirmed by urethroscopy during anticipated repair, without preoperative urethrography. The most common repairs for neourethra stricture after hypospadias surgery are single-stage dorsal inlay graft and 2-stage labial mucosa replacement urethroplasty., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Teaching and learning hypospadias repair is a major component of pediatric urology fellowship training. Educators must transfer skills to fellows, without increasing patient complications. Nevertheless, few studies report results of surgeons during their first years of independent practice., Purpose: To review outcomes of distal hypospadias repairs performed during the same 2-year period by consecutive, recently matriculated, surgeons in independent practice, and to compare them to results by their mentor (with >20 years of experience)., Materials: Exposure to hypospadias surgery during fellowship was determined from case logs of five consecutive fellows completing training from 2007-2011. TIP was the only technique used to repair distal hypospadias. No fellow operated independently or performed complete repairs under supervision. Instead, the first 3 months were spent assisting their mentor, observing surgical methodology and decision-making. Then, each performed selected portions under direct supervision, including: degloving, penile straightening, developing glans wings, incising and tubularizing the urethral plate, creating a barrier layer, sewing the glansplasty, and skin closure. Overall fellow participation in each case was <50%. In 2011-2012, urethroplasty complications (fistula, glans dehiscence, meatal stenosis, urethral stricture, diverticulum) were recorded for consecutive patients undergoing primary distal repair by these recent graduates in their independent practices. The fellow graduating in 2011 provided 1 year of data. All patients undergoing repair during the study period were included in the analysis, except those lost to follow-up after catheter removal. Composite urethroplasty complications were compared between junior surgeons, and between junior surgeons and their mentor, with Fisher's exact contingency test., Results: Training logs indicated fellow participation ranged from 76-134 hypospadias repairs, including distal, proximal and reoperative surgeries. Post-graduation case volumes ranged from 25-68 by junior surgeons versus 136 by the mentor. With similar mean follow-up, urethroplasty complication rates were statistically the same between the former fellows, and between them versus the mentor, ranging from 5-13%. Nearly all were fistulas or glans dehiscence. Junior surgeons reported they performed TIP as learned during fellowship, with one exception who used 7-0 polydioxanone rather than polyglactin for urethroplasty., Discussion: This is the first study directly comparing hypospadias surgical outcomes by recently graduated fellows in independent practice with those of their mentor. We found junior surgeons achieved similar results for distal TIP hypospadias repair. Although their participation during training largely comprised observation and surgical assistance, with discrete performance of key steps, skills sufficient to duplicate the mentor's results were transferred. These data suggest there should be no learning curve for distal hypospadias after training. This report raises several considerations for surgical educators. First, mentors should review their own results, to be certain that they are correctly performing and teaching procedures. Second, programs need to determine key steps for procedures they teach, and then emphasize their optimal performance. Finally, mentors should expect former fellows to report back their initial results of hypospadias repair to be certain lessons taught were learned. Otherwise, preventable complications resulting from technical errors will be multiplied in the children operated by their trainees as they enter independent practice., (Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: Current outcome tools for hypospadias have limited focus on the caregiver or patient perspective of important patient centered outcomes. In this study we collaborated with patients, caregivers, and lay and medical experts to develop and pilot a patient reported outcome measure for hypospadias., Materials and Methods: We developed a patient reported outcome measure based on systematic review of the literature and focus group input. The patient reported outcome measure was piloted in caregivers for boys younger than 8 years and in patients older than 8 years who presented for urology consultation before meeting with the surgeon. Patients were classified with uncorrected hypospadias, successful repair or failed repair based on the presence or absence of complications (fistula, diverticulum, meatal stenosis/stricture, greater than 30-degree recurrent curvature, glans dehiscence and/or skin reoperation)., Results: A patient reported outcome measure was developed and administered to 347 patients and/or caregivers-proxies, including 105 uncorrected cases, 162 successful repair cases and 80 failed cases. Satisfaction with appearance was highest in those with successful hypospadias repair compared to failed repair and uncorrected hypospadias (93% vs 77% and 67%, respectively). Voiding symptoms such as spraying or a deviated stream were highest in failed and uncorrected cases (39% and 37%, respectively). Overall dissatisfaction with voiding was highest for uncorrected hypospadias and failed repair compared to successful cases (54% and 47%, respectively, vs 15%)., Conclusions: The evaluation of patient and caregiver-proxy reported outcomes in preoperative and postoperative patients with hypospadias allows for the quantification of benefits derived from hypospadias repair and may ultimately represent the gold standard outcome measure for hypospadias. This pilot study identified preliminary patient centered themes and demonstrated the feasibility of administering hypospadias patient reported outcome measures in clinical practice., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: We hypothesized small glans size could increase urethroplasty complications (UC) following hypospadias repair. To test this, we measured glans width at its widest point in consecutive patients with hypospadias, and following a protocol for surgical decision-making, we then assessed post-operative UC using pre-determined definitions. We now report analysis of glans size as a potential additional independent risk factor for UC after hypospadias repair., Methods: Consecutive prepubertal patients undergoing hypospadias repair (2009-2013) had maximum glans width measured using calipers (Fig. 1). There were no differences in surgical technique for urethroplasty or glansplasty in this series based on the measured size of the glans. Multivariate logistic regression analyzed UC (fistula, glans dehiscence, diverticulum, stricture and/or meatal stenosis) based on glans size while adjusting for patient age, meatus (distal or midshaft/proximal), type of repair (TIP, inlay, 2-stage), surgeon, and primary or reoperative repair. Glans size was analyzed as both a continuous and dichotomous variable, with small glans defined as <14 mm., Results: Mean glans size was 15 mm (10-27 mm) in 490 boys (mean 1.5 years) undergoing 432 primary repairs (380d/19mid/33prox), and 58 reoperations (28d/7mid/23prox). Increasing age between 3 months and 10 years did not correlate with increasing glans size (R = 0.01, p = 0.18). 17% had small glans <14 mm. UC occurred in 61 (13%) primary TIP, 2-stage, and reoperative repairs, including 20/81 (25%) patients with small glans <14 mm, versus 41/409 (10%) in patients with glans width ≥14 mm (p = 0.0003). On multivariate analysis, small glans size (OR 3.5, 95% CI 1.8-6.8), reoperations (OR 3.0, 95% CI 1.4-6.5) and mid/proximal meatus (OR 3.1, 95% CI 1.6-6.2) were independent risk factors for UC. Surgeon, repair type, and patient age did not impact risk for UC. Analysis with glans size as a continuous variable demonstrated each 1 mm increase in size decreased odds of UC (OR 0.8, 95% CI 0.7-0.9)., Conclusions: Our analysis of prospectively-collected data from a standardized management protocol in 490 consecutive boys undergoing hypospadias repair adds small glans size, defined as width <14 mm, to proximal meatal location and reoperation as an independent risk factor for UC. Best means to modify this factor remain to be determined. Our data suggest that others analyzing potential risks for hypospadias UC should similarly measure and report glans width., (Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: Laparoscopic hernia repair with percutaneous ligation of the patent processes vaginalis is a minimally invasive alternative to open inguinal herniorrhaphy in children. With the camera port concealed at the umbilicus, this technique offers an excellent cosmetic result. It is also faster than the traditional laparoscopic repair with no differences in complication rates or hospital stay. The goal of this study was to describe a series of consecutive patients, emphasizing the impact of suture materials (absorbable vs. non-absorbable) on hernia recurrences., Methods: A retrospective review was performed of consecutive transperitoneal laparoscopic subcutaneous ligations of a symptomatic hernia and/or communicating hydrocele by 4 surgeons. Patients > Tanner 2 or with prior hernia repair were excluded. The success of the procedure and number of sutures used was compared between cases performed with absorbable vs. non-absorbable suture. Risk factors for surgical failure (age, weight, number of sutures used, suture type) were assessed with logistic regression., Results: 94 patients underwent laparoscopic percutaneous hernia ligation at a mean age of 4.9 years. Outcomes in 85 (90%) patients with 97 hernia repairs at a mean of 8 months after surgery revealed 26% polyglactin vs 4% polyester recurrences (p = 0.004) which occurred at mean of 3.6 months after surgery, Table 1. Repairs performed with non-absorbable suture required only 1 suture more often than those performed with absorbable suture (76% vs 60%, p = 0.163). Logistic regression revealed suture type was an independent predictor for failure (p = 0.017). Weight (p = 0.249), age (p = 0.055), and number of sutures (p = 0.469) were not significantly associated with recurrent hernia., Discussion: Our review of consecutive hernia repairs using the single port percutaneous ligation revealed a significantly higher recurrent hernia rate with absorbable (26%) versus non-absorbable (4%) suture. This finding remained significant in a logistic regression model irregardless of number of sutures placed, age, and weight. Though the authors acknowledge the drawback of the potential for learning curve to confound our data, we still feel these findings are clinically important as this analysis of outcomes has changed our surgical practice as now all providers involved perform this procedure with exclusively non-absorbable suture. We thus suggest that surgeons who perform this technique, especially those newly adopting it, use non-absorbable suture for optimal patient outcomes., Conclusions: Recurrent hernia after laparoscopic percutaneous hernia ligation was significantly lower in repairs performed with non-absorbable suture. Based on this data, we recommend the use of non-absorbable suture during laparoscopic ligation of inguinal hernias in children., (Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background/objectives: Patterns of postabsorptive adipose tissue fatty acid storage correlate with sex-specific body fat distribution. Some proteins and enzymes participating in this pathway include CD36 (facilitated transport), acyl-CoA synthetase (ACS; the first step in fat metabolism) and diacylglycerol acetyltransferase (DGAT; the final step of triglyceride synthesis). Our aim was to better define CD36, ACS and DGAT in relation to sex, subcutaneous fat depots and adipocyte size., Subjects/methods: Data were collected from studies conducted at Mayo Clinic between 2004 and 2012. Abdominal and femoral subcutaneous fat biopsy samples must have been collected in the postabsorptive state from healthy males and premenopausal females. Body composition was measured with dual-energy X-ray absorptiometry and abdominal computerized tomography scans. Adipocyte size (microscopy), CD36 protein content (enzyme-linked immunosorbent assay) and ACS and DGAT enzyme activities were measured. Data are presented as medians and 25th, 75th quartiles., Results: Males (n=60) and females (n=78) did not differ by age (37; 28, 46 years), body mass index (28.4; 24.6, 32.1 kg m(-)(2)) or abdominal (0.60; 0.45, 0.83 μg lipid per cell) and femoral adipocyte size (0.76; 0.60, 0.94 μg lipid per cell). Femoral ACS and DGAT were greater in females than males when expressed per mg lipid (ACS: 73 vs. 55 pmol/mg lipid/min; DGAT: 5.5 vs. 4.0 pmol/mg lipid/min; P<0.0001 for both) and per 1000 adipocytes (ACS: 59 vs. 39 pmol per min per 1000 adipocytes; DGAT: 4.3 vs 3.1 pmol per min per 1000 adipocytes; P⩽0.0003 for both). There were no differences in abdominal fat storage factors between sexes. ACS and DGAT decreased as a function of adipocyte size (P<0.0001 for both). The decrease in ACS was greater in males and abdominal subcutaneous fat. There were no sex differences in CD36 in either fat depot, nor did it vary across adipocyte size., Conclusions: Facilitated transport of fatty acids by CD36 under postabsorptive conditions would not be different in those with large vs small adipocytes in either depot of both sexes. However, intracellular trafficking of fatty acids to triglyceride storage by ACS and DGAT may be less efficient in larger adipocytes.

Objectives: 2011 American Academy of Pediatrics guidelines recommended renal-bladder ultrasound (RBUS) as the only evaluation after febrile urinary tract infection (FUTI) in infants aged 2-24 months. We determined the sensitivity, specificity, and false negative rate of RBUS to identify DMSA-detected renal damage in this age group as well as in older children., Methods: Consecutive patients referred to pediatric urology with a history of FUTI underwent DMSA ≥ 3 months after FUTI. Abnormal RBUS was defined as: Society of Fetal Urology hydronephrosis grades I-IV; hydroureter ≥ 7 mm; renal scar defined as focal parenchymal thinning; and/or size discrepancy ≥ 1 cm between kidneys. Abnormal DMSA was presence of any focal uptake defects and/or split renal function < 44%. We calculated sensitivity, specificity, positive and negative predictive values, and false negative rates of RBUS compared to DMSA., Results: 618 patients (79% female), median age 3.4 years, were referred for FUTIs. Of the 512 (83%) with normal RBUS, 99 (19%) had abnormal DMSA. Children with normal RBUS after their first FUTI had abnormal DMSA in 15/151 (10%) aged ≤ 24 months and 23/119 (19%) aged > 24 months. RBUS had poor sensitivity (34%) and low positive predictive value (47%) to identify patients with renal damage. 99/149 (66%) children with renal damage on DMSA had normal RBUS., Conclusion: After FUTI, 66% of children with reduced renal function and/or renal cortical defects found by DMSA scintigraphy had a normal RBUS. Since abnormal DMSA may correlate with increased risk for VUR, recurrent FUTI and renal damage, our data suggest RBUS alone will fail to detect a significant proportion of patients at risk. The data suggest that imaging after FUTI should include acute RBUS and delayed DMSA, reserving VCUG for patients with abnormal DMSA and/or recurrent FUTI., (Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Coronal fistulas present a potential dilemma in management. Successful closure requires reoperative glansplasty when there is only a thin band of tissue separating the urethral meatus from the fistula, indicating glans dehiscence. However, we avoided reoperative glansplasty during coronal fistula repair when the glans wings remained well-fused, given the increased risk for complications, including recurrent fistula, following reoperative glansplasty., Purpose: We report coronal fistula closure without reoperative glansplasty in patients with preserved fusion of the glans wings. We also compare this closure done with versus without postoperative urinary diversion. The primary outcome was recurrent fistula., Materials: Consecutive patients with coronal fistula and no glans dehiscence (Figure) underwent repair by dissecting the fistula tract under the glans rather than re-opening the glans wings. A midline incision facilitated creation of a ventral dartos barrier flap, used in all cases, as well as selective skin revision when needed. Initial patients had postoperative urinary diversion, whereas later consecutive patients did not. Data was recorded prospectively at the time of service into a database., Results: WS performed 122 fistula repairs from 2001 to 2013, of which 78 were coronal. Of these, 33 had glans dehiscence with only a thin band of skin separating the fistula from the distal meatus and underwent reoperative hypospadias repair. The other 45 met inclusion criteria with maintained glans wings fusion and had only fistula closure. These 45 patients all had fistulas

Objective: We report the time when hypospadias urethroplasty complications (UC) were diagnosed postoperatively., Methods: The time UC occurred after primary distal and proximal TIP and TIP reoperations was obtained from prospectively maintained databases in consecutive patients. UC included fistulas, glans dehiscences, meatal stenoses, neourethral strictures and diverticula., Results: Of 125 UC, 64% were diagnosed at the first postoperative visit and 81% were encountered within the first year after repair. Median time for diagnosis was 6 months (1.5-95) for fistulas, meatal stenoses/urethra strictures, and diverticulum, versus 2 months (1 week-24 months) for glans dehiscence., Conclusions: The majority of UC are diagnosed at the first postoperative visit or within the first year following TIP hypospadias repair. Glans dehiscences are most often apparent by 2 months, whereas most fistulas and other UC are found by 6 months. After 1 year, 14 boys without UC have to be followed indefinitely to diagnose each additional complication., (Published by Elsevier Ltd.)

Objective: We report preoperative testosterone stimulation based on glans width measurements in patients with midshaft and proximal hypospadias, revealing androgen resistance in those with proximal hypospadias., Methods: Patients had maximum glans width measured preoperatively. Those <14 mm initially received 2 mg/kg testosterone cypionate intramuscularly for two to three doses, with the aim of increasing glans width ≥ 15 mm. Not all patients achieved targeted growth, and some were subsequently treated with escalating doses of testosterone., Results: 5/15 midshaft patients had two to three doses of 2 mg/kg testosterone, with all increasing glans width to ≥ 15 mm. 29/47 proximal patients had testosterone, with 13 (57%) not reaching desired glans width. Six of these and another six patients had escalating doses from 4 to 32 mg/kg testosterone, with 11 then achieving targeted glans width. Relative androgen resistance was found in 19/29 (66%) proximal cases, including all treated patients with perineal hypospadias., Conclusions: 39/62 (63%) patients met objective criteria for preoperative testosterone stimulation based on glans width <14 mm, which is less than the average normal newborn glans diameter. Evidence of relative androgen resistance was found in 19 (49%), all with proximal hypospadias., (Published by Elsevier Ltd.)

Unlabelled: What is already known about this subject Children born to women with gestational diabetes have greater risk for obesity. Obesity in adults and children is associated with blunted postprandial gut hormone responses. What this study adds Children of women with gestational diabetes have a blunted postprandial response of GLP-1. Children of women with gestational diabetes have high fasting PYY concentrations., Background: Intrauterine exposure to gestational diabetes mellitus (GDM) increases risk for obesity. Obesity is associated with a blunted postprandial gut hormone response, which may impair satiety and thereby contribute to weight gain. The postprandial response of gut hormones among children of women with GDM has not previously been investigated., Objective: To examine whether children of women with GDM have suppressed peptide-tyrosine-tyrosine (PYY) and glucagon-like-peptide-1 (GLP-1), and higher concentrations of ghrelin, following a meal challenge. A secondary objective was to investigate associations of these hormones with children's free-living energy intake., Methods: Children (n = 42) aged 5-10 years were stratified into two groups: offspring of GDM mothers (OGD) and of non-diabetic mothers (CTRL). Body composition was measured by dual-energy X-ray absorptiometry, and circulating PYY, GLP-1 and total ghrelin were measured during a liquid meal challenge. Energy intake was assessed by three 24-h diet recalls., Results: Between-groups analyses of fasting and incremental area under the curve (AUC) found no differences in ghrelin. Incremental AUC for GLP-1 was greater among the CTRL vs. OGD (P < 0.05), and fasting PYY, but not incremental AUC, was higher among OGD vs. CTRL (P < 0.01). Associations of fasting and incremental AUC for each gut hormone with children's usual energy intake did not differ significantly by group., Conclusions: Further research is needed to more fully examine the potential role of postprandial GLP-1 suppression and high-fasting PYY concentrations on the feeding behaviour and risk for obesity among children exposed to GDM in utero., (© 2013 The Authors. Pediatric Obesity © 2013 International Association for the Study of Obesity.)

Objective: In the fasting state, plasma free fatty acids (FFA) are thought to derive almost exclusively from adipose tissue lipolysis. However, there are mixed reports as to whether the spillover of fatty acids (FA) from very low-density lipoprotein triglyceride (VLDL-TG) hydrolysis contributes significantly to the plasma FFA pool. Because substantial VLDL-TG fatty acid spillover into the plasma FFA pool would profoundly impact the interpretation of isotope dilution measures of FFA flux, we investigated the contribution of VLDL-TG spillover to plasma FFA appearance., Materials/methods: Eighteen obese adults (15 women) participated in these studies. Each volunteer received a primed, continuous infusion of their own ex-vivo labeled ([1-(14)C]triolein) VLDL-TG and a continuous infusion of [U-(13)C]oleate (8 nmol · kg fat free mass(-1) · min(-1)) to measure VLDL-TG and FFA rate of appearance (Ra), respectively. The presence of (14)C-oleate in the plasma FFA-oleate pool was used to calculate the contribution of spillover from VLDL-TG-oleate to the plasma FFA-oleate Ra., Results: The spillover rate of VLDL-TG-oleate into plasma FFA-oleate was 6 ± 2 μmol/min (7% ± 2% of [(14)C]oleate from VLDL-TG) and FFA-oleate flux was 240 ± 61 μmol/min. Thus, only 3% ± 1% of total plasma FFA-oleate appearance could be accounted for by VLDL-TG spillover., Conclusion: The contribution of VLDL-TG spillover to the total plasma FFA pool is negligible and will not materially affect the interpretation of FFA flux measures as an index of adipose tissue lipolysis., (© 2013.)

Introduction: We previously described urethral plate (UP) dissection and urethral mobilization from the corpora cavernosa to achieve or facilitate straightening ventral curvature while preserving the UP for TIP in boys with proximal hypospadias. The original patients had similar complications to those undergoing proximal TIP without UP elevation. Subsequently an increased occurrence of neourethra strictures in those with UP elevation and urethral mobilization was recognized, and is now reported., Materials: Information on consecutive patients with proximal TIP repair with and without UP elevation and urethral mobilization by a single surgeon was reviewed in a database with pre-determined data points entered on the day of service., Results: There were 76 proximal TIP patients with follow up, 29 with and 47 without UP elevation and urethral mobilization, with strictures developing in 5 (17%) and 0, respectively, p = 0.01. All strictures were symptomatic (UTI, urinary retention), 0.1-1.0 cm long, and diagnosed at ≤1.5 years after surgery., Conclusions: UP elevation and urethral mobilization with TIP resulted in focal devascularization of the neourethra with symptomatic stricture development. Although most patients with these straightening maneuvers did not have stricture, we no longer recommend UP elevation and urethral mobilization with proximal TIP repair., (Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the reliability and internal validity of the Hypospadias Objective Penile Evaluation (HOPE)-score, a newly developed scoring system assessing the cosmetic outcome in hypospadias., Patients and Methods: The HOPE scoring system incorporates all surgically-correctable items: position of meatus, shape of meatus, shape of glans, shape of penile skin and penile axis. Objectivity was established with standardized photographs, anonymously coded patients, independent assessment by a panel, standards for a "normal" penile appearance, reference pictures and assessment of the degree of abnormality. A panel of 13 pediatric urologists completed 2 questionnaires, each consisting of 45 series of photographs, at an interval of at least 1 week. The inter-observer reliability, intra-observer reliability and internal validity were analyzed., Results: The correlation coefficients for the HOPE-score were as follows: intra-observer reliability 0.817, inter-observer reliability 0.790, "non-parametric" internal validity 0.849 and "parametric" internal validity 0.842. These values reflect good reproducibility, sufficient agreement among observers and a valid measurement of differences and similarities in cosmetic appearance., Conclusions: The HOPE-score is the first scoring system that fulfills the criteria of a valid measurement tool: objectivity, reliability and validity. These favorable properties support its use as an objective outcome measure of the cosmetic result after hypospadias surgery., (Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: There are no reports of systematically-measured penile dimensions in boys with varying extents of hypospadias. To determine reference values, we prospectively measured maximum glans width in patients undergoing distal and proximal hypospadias repair as well as newborns undergoing elective circumcision., Methods: The maximum glans diameter was measured in consecutive boys aged 0-24 months presenting for newborn circumcision (controls), or repair of distal (distal shaft or glanular) and proximal (proximal shaft to perineal) hypospadias. Patients with proximal hypospadias and glans diameter <14 mm received intramuscular testosterone 2 mg/kg injection once monthly for 2-3 treatments, with measurements recorded prior to the first injection, and again intra-operatively 3-4 weeks after the final injection., Results: Data were obtained in 240 controls, 188 boys with distal hypospadias, and 39 boys with proximal hypospadias. Median ages were 1, 9 and 9 months, respectively. Males undergoing newborn circumcision were younger than both cohorts of hypospadias patients (p < 0.0001), but no difference in age was noted in those with distal and proximal hypospadias (p = 0.194). Average maximum glans diameters were significantly different: 14.3, 14.8, and 12.9 mm, respectively, for controls, distal and proximal hypospadias (p < 0.0001). Despite mean older age, 46 (24.5%) boys with distal hypospadias and 24 (61.5%) with proximal hypospadias had small glans diameter <14 mm. Increasing age was not correlated with increasing glans size in patients with distal or proximal hypospadias (r = -0.136, p = 0.062 and r = -0.089, p = 0.580) at 3-24 months of age., Conclusion: Some boys with distal and the majority of those with proximal hypospadias have a glans width less than that of the average normal newborn. Glans size does not correlate with age in patients with hypospadias between 3 and 24 months old, supporting the decision to operate as early as 3 months in some centers., (Copyright © 2013. Published by Elsevier Ltd.)

Purpose: To determine prevalence and risk factors for renal scar in children referred for urologic assessment of febrile UTI and/or VUR., Methods: Pre-determined risk factors for renal scar were prospectively recorded in consecutive patients referred for UTI/VUR. Age, gender, VUR grade, and reported number of febrile and non-febrile UTIs were analyzed with logistic regression to determine risk for focal cortical defects on non-acute DMSA., Results: Of 565 consecutive children, 24 (4%) had congenital renal dysplasia and 84 (15.5%) had focal defect(s). VUR, especially grades IV-V, recurrent febrile UTI, and older age increased risk. For any age child with the same number of UTIs, VUR increased odds of renal defect 5.4-fold (OR = 5.4, 95% CI = 2.7-10.6, AUC = 0.759)., Conclusions: Focal DMSA defects were present in 15.5% of 565 consecutive children referred for febrile UTI and/or VUR; 4% had presumed congenital reflux nephropathy without cortical defect. All VUR grades increased risk for these defects, as did recurrent febrile UTIs and older age. However, 43% with grades IV-V VUR and 76% with recurrent UTI had normal DMSA., (Published by Elsevier Ltd.)

Objective: Polyethylene glycol (PEG) is common first-line therapy for urinary symptoms despite minimal evidence-based support. We performed a randomized, double-blind, placebo-controlled study of PEG for initial treatment of overactive bladder (OAB) symptoms in children., Patients and Methods: Patients aged >3 years underwent baseline urinary symptom questionnaire (USQ, scored 0-16), bowel symptom questionnaire (scored 0-20) and abdominal X-ray (KUB). Patients were randomized to placebo/PEG regardless of parent's perception of constipation. After 1 month, patients completed follow-up questionnaires and KUB. Improvement was defined as decrease in USQ (ΔUSQ) ≥ 3 points. Secondary analyses compared urinary and bowel symptoms to KUB., Results: Of 138 enrolled patients, 71 (51.4%) completed 1 month of therapy. Analyses of those randomized to placebo vs. PEG and non-completers demonstrated similar demographics, baseline symptoms, and KUB. Patients treated with placebo and PEG both had significant improvement in USQ scores (p < 0.0001). Patients treated with placebo and PEG responded similarly to placebo (ΔUSQ 3.7 vs. 3.4, p = 0.773), with improvement in nearly half (48.5% PEG vs. 44.7% placebo). There was no correlation between KUB and urinary or bowel symptoms., Conclusions: Nearly 50% of patients with urinary urge symptoms treated with either placebo or PEG for 1 month had improvement in urinary symptoms. KUB did not correlate with baseline or follow-up urinary or bowel symptoms., (Copyright © 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: Patients often present before or after the recommended age of 6-18 months for hypospadias repair. Reports indicate complications may increase when repair is delayed past 6-12 months of age. We questioned if age was an independent risk for urethroplasty complications (UC)., Methods: A prospectively maintained database of consecutive patients undergoing tubularized incised plate (TIP) repair was queried for age at surgery, primary or reoperative TIP, meatal location, glansplasty suture, and learning curve. The presence of UC (fistula, dehiscence, stricture, meatal stenosis) was analyzed with logistic regression., Results: TIP repairs were performed for 669 consecutive prepubertal patients aged 3-144 months (mean 17.1, SD 22.5). Original meatal location was distal in 540 (80.7%), midshaft in 50 (7.5%), and proximal in 79 (11.8%). Reoperative TIP occurred in 73 (10.9%). UC occurred in 77 (11.5%). Reoperative TIP (OR 3.07, 95% CI 1.54-6.13) and meatal location (OR 1.79, 95% CI 1.34-2.40) were the only independent risk factors for UC. Neither younger nor older age increased risk for UC., Conclusions: Our data from consecutive TIP repairs in prepubertal children indicate age at surgery does not increase odds of UC. Surgery can be performed any time after 3 months (in full-term, healthy boys) without raising the rate of UC., (Published by Elsevier Ltd.)

Background: Risk for obesity differs with ethnicity/race and is associated with insulin sensitivity (SI), insulin responsiveness, and dietary glycemic load (GL). The objective of this study was to test the hypotheses that, 1) obesity-prone, normal weight, African-American (AA) women would be more insulin sensitive than BMI-matched, never overweight AA women; 2) increased adiposity over time would be associated with greater baseline SI and higher dietary GL in AA but not European-American (EA) women; and 3) increased adiposity over time would be predicted by SI in women with high but not low acute insulin response to glucose (AIRg)., Methods: Two controlled weight loss interventions were conducted involving overweight (BMI 25.0-29.9 kg/m2) premenopausal AA and EA women. The first included matching with normal-weight (BMI <25.0 kg/m2) controls following weight loss, and then comparing SI. The second included a 1-year follow-up of weight-reduced participants to identify predictors of change in %body fat. Main outcome measure in the first study was insulin sensitivity (SI) as assessed with intravenous glucose tolerance test (IVGTT), and in the second study was change in %fat, as assessed with DXA, over one year. AIRg was assessed during IVGTT, and free-living diet was determined by food record., Results: In the first study, formerly overweight AA women were 43% more insulin sensitive than BMI-matched never overweight AA (P < 0.05). In the second study, SI was positively associated with change in %fat over 1 year only in AA women (P < 0.05) and women with high AIRg (P < 0.05). In addition, AA who were insulin sensitive and who consumed a higher GL diet tended to gain greater %fat (P = 0.086 for diet x SI interaction). In both studies, AA women had higher AIRg (P < 0.001) than EA women., Conclusions: Formerly overweight (obesity-prone) AA women were more insulin sensitive than never overweight AA women, a quality that may predispose to adiposity, particularly when combined with a high GL diet. This ethnicity/race-specific effect may be due to high insulin responsiveness among AA.

Context: A central/visceral fat distribution and excess free fatty acid (FFA) availability are associated with dyslipidemia and insulin resistance. However, these two characteristics often coexist, making it difficult to detect the independent contributions of each. Whether FFA suppression is more closely linked to metabolic abnormalities is not clear., Objective: The aim of the study was to examine the relationship between FFA suppression, body fat distribution, and fitness as contributors toward insulin resistance and hypertriglyceridemia., Design: We measured systemic palmitate turnover using an iv infusion of [9,10-(3)H]palmitate; upper body sc adipose tissue (UBSQ) and visceral adipose tissue (VAT) with dual-energy x-ray absorptiometry and a single-slice abdominal computed tomography scan; fitness with a graded exercise treadmill test; and insulin sensitivity with both the iv glucose tolerance test (IVGTT) (SI(IVGTT)) and mixed meal tolerance test (SI(Meal))., Setting: The study was conducted at a General Clinical Research Center., Participants: Baseline data were obtained from 140 elderly adults (age, 60-88 yr; 83 males) and 60 young adults (age, 18-31 yr; 31 males) who participated in a previously published trial assessing the effects of 2-yr supplementation of dehydroepiandrosterone or testosterone on body composition, glucose metabolism, and bone density., Interventions: There were no interventions., Main Outcome Measures: We measured fasting plasma triglyceride (TG) concentrations, SI(IVGTT), and SI(Meal)., Results: Using multivariate regression analysis, the strongest combined predictors of TG concentrations were VAT, postmeal nadir FFA concentrations, sex, and age. The best predictors of SI(IVGTT) were IVGTT nadir palmitate concentration, VAT, UBSQ fat, fitness, and age, whereas the best predictors of SI(Meal) were meal nadir palmitate concentration, UBSQ fat, fitness, and sex., Conclusions: FFA suppression is associated with both fasting TG concentrations and insulin sensitivity, independent of measures of adiposity.

Purpose: Historically the placement of testicular prosthesis during orchiectomy for torsion is delayed despite reports of safe prosthesis placement during mastectomy and orchiectomy for cancer as well as the removal of infected penile prostheses. We describe our experience with intravaginal testicular prosthesis at orchiectomy in adolescents with torsion., Materials and Methods: Consecutive pubertal patients undergoing exploration for torsion from 2010 to 2011 were offered orchiectomy with staged prosthesis or combined orchiectomy and prosthesis exchange for nonsalvageable testis. Through a midline scrotal incision the ipsilateral tunica vaginalis was opened, testis detorsed and contralateral orchiopexy performed. When verified as unviable, the ipsilateral spermatic cord was suture ligated within the tunica vaginalis and preplaced sutures secured the saline filled prosthesis in the tunica vaginalis. Patients were discharged home on the day of surgery with 5 days of oral antibiotics and narcotics. Demographic, surgical and postoperative measures were prospectively recorded., Results: Of 19 patients 6 had testes deemed salvageable at surgery with a median time to presentation of 6 hours (range 4 to 48) vs 96 (range 14 to 168, p = 0.002) in the 13 patients with nonsalvageable torsion. Of these patients 12 (median age 15 years, range 12 to 16) elected combined orchiectomy and prosthesis exchange. With a median followup of 4.8 months (range 1.5 to 16) there were no infectious complications or extrusions. Eleven (91.7%) patients had a symmetric appearing scrotum with the prosthesis located in a mid to dependent scrotal position., Conclusions: We demonstrate the feasibility of intravaginal prosthesis placement for immediate scrotal reconstruction in adolescents with nonsalvageable testicular torsion. Advantages of combined orchiectomy and prosthesis exchange include orthotopic prosthetic position, extra tunica vaginalis barrier layer and avoidance of a second anesthetic., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Offspring of women with gestational diabetes (OGD) have greater risk for obesity and impaired metabolic health. Whether impaired metabolic health occurs in the absence of obesity is not clear., Objective: The purpose of this study was to investigate the independent and interactive effects of intrauterine exposure to gestational diabetes and of children's current weight status on their metabolic health., Methods: Children aged 5–10 years (n = 51) with and without intrauterine exposure to gestational diabetes (OGD vs. offspring of non-diabetic women [CTRL]) were grouped into normal weight (body mass index [BMI] < 85th %) and overweight (BMI > 85th %) according to Centers for Disease Control growth curves. Lipid profile was obtained by fasting blood draw, insulin sensitivity (SI) and secretion by liquid meal tolerance test, and body composition by dual-energy X-ray absorptiometry., Results: Despite similar average BMI percentiles among normal weight OGD versus CTRL, and overweight OGD vs. CTRL, OGD had greater total %fat and trunk fat adjusted for leg fat compared with CTRL (P < 0.05). Overweight children had lower SI (P < 0.05) and greater basal, static, and total insulin secretion independent of SI (P < 0.05). OGD was independently associated with greater static insulin secretion (P < 0.05) and the interaction between OGD and overweight was associated with greater basal insulin secretion independent of SI (P < 0.01). OGD and overweight were each associated with lower high-density lipoprotein-cholesterol (HDL-C) (P < 0.05)., Conclusion: Intrauterine exposure to gestational diabetes was associated with greater central adiposity and insulin secretion, and lower HDL-C, irrespective of current weight status. Future research should examine respective contributions of the intrauterine environment and of underlying genotype on children's metabolic health.

Purpose: While the timely diagnosis and management of pediatric torsion can lead to testicular salvage, limited data exist on rates of orchiopexy vs orchiectomy and associated factors. Thus, we examined the Pediatric Health Information System database for torsion outcomes and demographics at American pediatric hospitals., Materials and Methods: Using the Pediatric Health Information System database we performed a 7-year retrospective cohort study in children 1 to 17 years old with a primary ICD-9 diagnosis of torsion, assessing CPT codes for orchiopexy and orchiectomy. Data were analyzed with SPSS®, version 17.0., Results: Of 2,876 patients who underwent surgery for an ICD-9 diagnosis code of testicular torsion 918 (31.9%) underwent orchiectomy at a mean age of 10.7 years and 1,958 (68.1%) underwent orchiopexy at a mean age of 12.6 years (p <0.0001). In the age groups 1 to 9, 10 to 13 and 14 years or greater 274 (49.9%), 311 (29.4%) and 333 patients (26.2%), respectively, underwent orchiectomy. A higher orchiectomy rate was seen at age 1 to 9 vs 10 years or greater. Torsion and orchiectomy rates did not vary by season or geographic region. A higher orchiectomy rate was seen in black vs white children (37.6% vs 28.1%) and in patients without vs with private insurance (36.7% vs 27.0%). Multivariate analysis revealed an association of age (p <0.0001), race (p <0.0001) and insurance status (p <0.001) with orchiectomy., Conclusions: Nationally an average of 32% of the 411 pediatric torsion cases explored annually result in orchiectomy. Identified factors increasing the orchiectomy risk included age 1 to 9 years, black race and lack of private insurance. Efforts should continue to identify modifiable variables that can increase testicular salvage in patients with testicular torsion., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose was to compare nephrolithiasis in healthy versus medically complex gastrostomy fed children., Materials and Methods: Children with nephrolithiasis with and without gastrostomy were identified by database searches from 1999 to 2009. Gastrostomy fed stone formers (GSF) were compared to an age-matched cohort of non-gastrostomy-fed stone formers (NGSF) for demographic and clinical data., Results: 16 neurologically impaired GSF (10M:6F), mean age 10.4 years (range 1.7-17.5 years), were compared to 32 matched neurologically intact NGSF. Compared to NGSF, GSF had significantly higher urine pH (6.93 vs 6.23, p = 0.001) and larger stones (14.5 vs 6.9 mm, p = 0.02) more commonly composed of calcium phosphate (7/11, 64% vs 3/28, 11%, p = 0.002). 15/16 (94%) of GSF were immobile while 0% of NGSF were immobile. GSF had lower l-spine bone density Z-scores (-3.02 vs -1, p = 0.002) but an equal rate of hypercalciuria (2/7, 29% vs 7/24, 29%, p = NS). Contributing lithogenic factors in 8/16 (50%) GSF included urinary tract infection (UTI) (5), lithogenic medications (2), and xanthinuria (1)., Conclusions: Stone disease in GSF is multifactorial, and half of our study group had an identifiable risk factor for nephrolithiasis. A recurring pattern of alkaline urine and calcium phosphate stone formation was evident. GSF did not have higher rates of hypercalciuria despite chronic immobilization and markedly lower bone density. An awareness of the potential risk factors identified is mandatory for this vulnerable population., (Copyright © 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)