Rab25 is involved in hypospadias via the ß1 integrin/EGFR pathway.

BACKGROUND: Hypospadias is a common congenital abnormality of the penile. Abnormal regulation of critical genes involved in urethral development leads to hypospadias. We used the Rab25-/- mice and foreskin fibroblasts transfected with lentivirus in vitro and in vivo to investigate the role of Rab25 in hypospadias. METHODS: The expression levels of various molecules in tissue samples and foreskin fibroblasts were confirmed using molecular biology methods (western blotting, PCR, immunohistochemistry, etc.). A scanning electron microscope (SEM) was used to visualize the external morphology of genital tubercles (GTs) of gestation day (GD) 18.5 male wild-type (WT) and Rab25-/- mice. RESULTS: An expanded distal cleft and V-shaped urethral opening were observed in GD 18.5 Rab25-/- mice. We demonstrated that Rab25 mediated hypospadias through the ß1 integrin/EGFR pathway. In addition, silencing Rab25 inhibited cell proliferation and migration and promoted apoptosis in the foreskin fibroblasts; Ki-67- and TUNEL-positive cells were mainly concentrated near the urethral seam. CONCLUSION: These findings suggest that Rab25 plays an essential role in hypospadias by activation of ß1 integrin/EGFR pathway, and Rab25 is a critical mediator of urethral seam formation in GD18.5 male fetal mice.

Retrospective studies and quantitative proteomics reveal that abnormal expression of blood pressure, blood lipids, and coagulation related proteins is associated with hypospadias.

Hypospadias refers to the abnormal position of the male urethral orifice, which not only leads to urination disorder but also causes sexual dysfunction in adulthood. However, the complex and diverse pathogenic factors of hypospadias are still unclear. To study the pathogenesis and prognosis of hypospadias, we counted the serological indexes of children with hypospadias, and found that sSBP, TC and LDL increased in children with mild, moderate and severe hypospadias. Subsequently, we used quantitative proteomics to find differential proteins in mild, moderate and severe hypospadias. After bioinformatics analysis and biochemical experiments on the screened DEPs, we found that the expression of proteins related to immune inflammation, coagulation, blood pressure and inflammation, and blood lipid were differential expressed in the prepuce tissue of children with hypospadias. We further confirmed that the proteins FGB, FGG, SERPINA1, and AGT involved in the angiotensin system, cholesterol metabolism, and coagulation were significantly up-regulated by biochemical experiments. In particular, the AGT protein of the angiotensin system involved in blood pressure regulation, we have shown that it increases with the severity of hypospadias. This study suggests that children with hypospadias are more likely to suffer from hyperlipidemia and cardiovascular disease (CVD). Our findings provide a theoretical basis for early monitoring of blood lipids and blood pressure to prevent CVD in children with hypospadias.

Meconium Concentrations of Pesticides and Risk of Hypospadias: A Case-Control Study in Brittany, France.

BACKGROUND: Hypospadias is a male genital tract defect for which an increase in prevalence has been documented over the last few decades. A role for environmental risk factors is suspected, including prenatal exposure to pesticides. OBJECTIVES: To study the risk of hypospadias in association with multiple pesticide measurements in meconium samples. METHODS: The Brittany Registry of Congenital Anomalies (France) conducted a case-control study between 2012 and 2018. Cases were hypospadias, ascertained by a pediatrician and a pediatric surgeon, excluding genetic conditions, following European Surveillance of Congenital Anomalies guidelines (N = 69). Controls (N = 135) were two male infants without congenital anomaly born after each case in the same maternity unit. Mothers in the maternity units completed a self-administered questionnaire, we collected medical data from hospital records, and medical staff collected meconium samples. We performed chemical analysis of 38 pesticides (parent compound and/or metabolite) by UHPLC/MS/MS following strict quality assurance/quality control criteria and blind to case-control status. We carried out logistic regression accounting for frequency-matching variables and major risk factors. RESULTS: Among the 38 pesticides measured, 16 (42%) were never detected in the meconium samples, 18 (47%) were in <5% of samples, and 4 (11%) in ≥5% of the samples. We observed an association between the detection of fenitrothion in meconium and the risk of hypospadias (OR = 2.6 [1.0-6.3] with n cases = 13, n controls = 21), but not the other pesticides. CONCLUSIONS: Our small study provides a robust assessment of fetal exposure. Fenitrothion's established antiandrogenic activities provide biologic plausibility for our observations. Further studies are needed to confirm this hypothesis.

Characterization of urethra closure in female neonatal mice at histological and molecular levels.

In brief: Female hypospadias is a little-known and poorly studied birth defect. This research establishes an anatomical and molecular foundation for future research to investigate the origins of this defect. Abstract: Hypospadias is a congenital anomaly of the external genitalia where the urethra does not properly close. In humans, hypospadias is mostly reported in male newborns, whereas in females hypospadias is rare, although it is generally considered to be under-reported. Improper urethra closure in the female genitalia can cause recurrent genitourinary tract infections and infertility. In mice, female hypospadias was induced by exposure to exogenous estrogenic compounds. Aside from the link between estrogen exposure and female hypospadias, the process of female urethra closure is largely unstudied, with the precise timing of urethra closure and associated molecular mechanisms remaining poorly understood. To address this gap, we determined when urethra closure occurs and identified gene expression patterns during the process of urethra closure in female neonatal mice from postnatal day (PND) 5 to 10. Using whole mount imaging and histology, we discovered that the initiation of urethra closure begins at PND7, and urethra closure is fully completed by PND10. To identify the genes associated with urethra closure, we conducted bulk RNA sequencing on female external genitalia prior to and after urethra closure. Gene ontology analyses revealed an increase in steroidogenic gene expression (Star, Hsd3b6, and Cyp17a1) during urethra closure, suggesting that the female genitalia locally produce steroids which could facilitate steroid signaling within the genitalia. With this study, we establish an anatomical timeline of female urethra closure and hypothesize a paracrine steroid signaling mechanism of urethra closure. These observations provide entry points to aid in further understanding external genital abnormalities, like hypospadias, in females.

A Japanese patient with Teebi hypertelorism syndrome and a novel CDH11 EC1 domain variant.

The gene CDH11 encodes cadherin-11, a Type II cadherin superfamily member that contains five extracellular cadherin (EC) domains. Cadherin-11 undergoes trans-dimerization via the EC1 domain to generate cadherin complexes. Compound heterozygous and homozygous loss-of-function CDH11 variants are observed in Elsahy-Waters syndrome (EWS), which shows characteristic craniofacial features, vertebral abnormalities, cutaneous syndactyly in 2-3 digits, genitourinary anomalies, and intellectual disability. Heterozygous CDH11 variants can cause Teebi hypertelorism syndrome (THS), which features widely spaced eyes and hypospadias. We report a THS patient with a novel CDH11 variant involving the EC1 domain. The patient was a 10-month-old male with normal developmental milestones, but had widely spaced eyes, strabismus, hypospadias, shawl scrotum, broad thumbs (right bifid thumb in x-ray), polysyndactyly of the left fourth finger, and cutaneous syndactyly of left third/fourth fingers. Exome sequencing identified a de novo heterozygous CDH11 variant (NM_001797.4:c.229C > T [p.Leu77Phe] NC_000016.9:g.64998856G > A). Clinical features were consistent with previously reported THS patients, but polysyndactyly, broad thumb, and cutaneous syndactyly overlapped phenotypic features of EWS. THS and EWS may represent a spectrum of CDH11-related disorders. Residue Leu77 in this novel CDH11 variant lines a large hydrophobic pocket where side chains of the partner cadherin-11 insert to trans-dimerize, suggesting that the cadherin-11 structure might be altered in this variant.

Maternal periconceptional folic acid supplementation and risk for fetal congenital genitourinary system defects.

BACKGROUND: Taking folic acid supplementation could reduce the risk of neural tube defects for offspring in the maternal periconceptional period, but the relationship between folic acid use and other birth defects remains unclear, such as genitourinary system birth defects. METHODS: The data from a Prenatal Health Care System and Birth Defects Surveillance System in Tongzhou, Beijing, China, were collected from 2013 to 2018. We adjusted for differences in characteristics between comparison groups using propensity score inverse probability weighting and assessed associations with Poisson regression modeling. RESULTS: A total of 65,418 live births and stillbirths were included, and there were 194 cases with congenital genitourinary defects among them. The prevalence of genitourinary system birth defects was 29.2 (34.9) per 10,000 for FA/MMFA users (nonusers). Compared to nonusers, FA/MMFA users had a lower risk for genitourinary system birth defects (adjusted risk ratio [aRR] 0.81, 95% confidence interval [CI] 0.67, 0.98), and for hypospadias (aRR 0.55, 95% CI 0.40, 0.76). CONCLUSIONS: FA or MMFA supplementation during the maternal periconceptional period could reduce the risk for genitourinary system birth defects in offspring. More mechanisms should be explored for the protective effect. IMPACT: Folic acid (FA) or multiple micronutrients containing folic acid (MMFA) supplementation during the maternal periconceptional period could reduce the risk for genitourinary system birth defects in offspring. Maternal FA/MMFA supplementation during the periconceptional period may reduce the risk for hypospadias.

Maternal physical activity, sitting, and risk of non-cardiac birth defects.

BACKGROUND: The relationship between maternal physical activity (PA)/sitting and birth defects is largely unexplored. We examined whether pre-pregnancy PA/sitting were associated with having a pregnancy affected by a birth defect. METHODS: We used data from two United States population-based case-control studies: 2008-2011 deliveries from the National Birth Defects Prevention Study (NBDPS; 9 states) and 2014-2018 deliveries from the Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS; 7 states). Cases with one of 12 non-cardiac birth defects (n = 3798) were identified through population-based registries. Controls (n = 2682) were live-born infants without major birth defects randomly sampled using vital/hospital records. Mothers self-reported pre-pregnancy PA/sitting. Unconditional logistic regression models estimated associations between PA/sitting categories and the 12 birth defects. RESULTS: Mothers engaging in pre-pregnancy PA was associated with a reduced odds of five (spina bifida, cleft palate, anorectal atresia, hypospadias, transverse limb deficiency) and a higher odds of two (anencephaly, gastroschisis) birth defects. Mothers spending less time sitting in pre-pregnancy was associated with a reduced odds of two (anorectal atresia, hypospadias) and a higher odds of one (cleft lip with or without cleft palate) birth defect. CONCLUSIONS: Reasonable next steps include replication of these findings, improved exposure assessment, and elucidation of biologic mechanisms. IMPACT: Using data from two population-based case-control studies, we found that mothers engaging in different types of physical activity in the 3 months before pregnancy had an infant with a reduced odds of five and a higher odds of two birth defects. Mothers spending less time sitting in the 3 months before pregnancy had an infant with a reduced odds of two and a higher odds of one birth defect. Clarification and confirmation from additional studies are needed using more precise exposure measures, distinguishing occupational from leisure-time physical activity, and elucidation of mechanisms supporting these associations.

Primary hypospadias repair outcomes: results from a retrospective cohort of 292 children.

PURPOSE: Hypospadias surgery is challenging. Numerous techniques have been described with variable complication rates. The main objectives of our study were to evaluate the urethroplasty complication rate of primary hypospadias repair and to identify risk factors for complications. METHODS: We retrospectively evaluated the outcomes of all patients who underwent primary hypospadias repair in our department between January 2012 and December 2020. Demographic, anatomical, operative, and postoperative data were reported. Univariate and multivariate logistic regression analyses were performed to identify variables associated with complications. Statistical significance was set at p < 0.05. RESULTS: Of 292 patients, 203 (69.5%) had distal hypospadias, 63 (21.6%) had mid-penile hypospadias, and 26 (8.9%) had proximal hypospadias. The mean age at the time of surgery was 22.8 months. Seventy-eight patients (26.7%) had urethroplasty complications. The rate of complications was higher for proximal hypospadias (57.7%), onlay island flap (44.4%), and Koyanagi (75%) procedures. The mean follow-up duration was 29 months. Two predictors of complications were identified by multivariate analysis: catheterization duration and urethroplasty technique. The reoperation rate was 30.5%. CONCLUSION: Urethroplasty complications frequently occur after primary hypospadias repair. The complication rate was higher in proximal hypospadias. Catheterization duration and surgical technique were significant predictors of complications. A longer and more standardized follow-up is needed for a better assessment of hypospadias repair outcomes.

Bias analyses to investigate the impact of differential participation: Application to a birth defects case-control study.

BACKGROUND: Certain associations observed in the National Birth Defects Prevention Study (NBDPS) contrasted with other research or were from areas with mixed findings, including no decrease in odds of spina bifida with periconceptional folic acid supplementation, moderately increased cleft palate odds with ondansetron use and reduced hypospadias odds with maternal smoking. OBJECTIVES: To investigate the plausibility and extent of differential participation to produce effect estimates observed in NBDPS. METHODS: We searched the literature for factors related to these exposures and participation and conducted deterministic quantitative bias analyses. We estimated case-control participation and expected exposure prevalence based on internal and external reports, respectively. For the folic acid-spina bifida and ondansetron-cleft palate analyses, we hypothesized the true odds ratio (OR) based on prior studies and quantified the degree of exposure over- (or under-) representation to produce the crude OR (cOR) in NBDPS. For the smoking-hypospadias analysis, we estimated the extent of selection bias needed to nullify the association as well as the maximum potential harmful OR. RESULTS: Under our assumptions (participation, exposure prevalence, true OR), there was overrepresentation of folic acid use and underrepresentation of ondansetron use and smoking among participants. Folic acid-exposed spina bifida cases would need to have been ≥1.2× more likely to participate than exposed controls to yield the observed null cOR. Ondansetron-exposed cleft palate cases would need to have been 1.6× more likely to participate than exposed controls if the true OR is null. Smoking-exposed hypospadias cases would need to have been ≥1.2 times less likely to participate than exposed controls for the association to falsely appear protective (upper bound of selection bias adjusted smoking-hypospadias OR = 2.02). CONCLUSIONS: Differential participation could partly explain certain associations observed in NBDPS, but questions remain about why. Potential impacts of other systematic errors (e.g. exposure misclassification) could be informed by additional research.

What should be next in lifelong posterior hypospadias: Conclusions from the 2023 ERN eUROGEN and EJP-RD networking meeting.

BACKGROUND: A congenital disease is for life. Posterior hypospadias, the severe form of hypospadias with a penoscrotal, scrotal, or perineal meatus, is a challenging condition with a major impact on lifelong quality of life. AIM: Our network meeting is aimed to identify what is currently missing in the lifelong treatment of posterior hypospadias, to improve care, quality of life, and awareness for these patients. METHODS: The network meeting "Lifelong Posterior Hypospadias" in Utrecht, The Netherlands was granted by the European Joint Programme on Rare Diseases-Networking Support Scheme. There was a combination of interactive sessions (hackathons) and lectures. This paper can be regarded as the last phase of the hackathon. RESULTS: Surgery for hypospadias remains challenging and complications may occur until adulthood. Posterior hypospadias affects sexual function, fertility, and hormonal status. Transitional care from childhood into adulthood is currently insufficiently established. Patients should be more involved in defining desired treatment approach and outcome measures. For optimal outcome evaluation standardization of data collection and registration at European level is necessary. Tissue engineering may provide a solution to the shortage of healthy tissue in posterior hypospadias. For optimal results, cooperation between basic researchers from different centers, as well as involving clinicians and patients is necessary. CONCLUSIONS: To improve outcomes for patients with posterior hypospadias, patient voices should be included and lifelong care by dedicated healthcare professionals guaranteed. Other requirements are joining forces at European level in uniform registration of outcome data and cooperation in basic research.

MicroR-1199-5p targeting SRD5A2 promotes the biological behavior and EMT of hypospadias cells.

Hypospadias, an oft-occurring penis anomaly, ranks among neonatal's foremost birth defects. The SRD5A2 can affect male reproductive system development and is abnormally expressed in its epithelial cells. This study exploration aimed at understanding the role of SRD5A2 in the development of hypospadias from a molecular perspective. SRD5A2 levels in hypospadias primary cells were analyzed by Western blot, while targeted interaction with miR-1199-5p was ascertained by dual-luciferase gene reporter assay. In vitro biological experiments were used to confirm the biological function of SRD5A2 in hypospadias. SRD5A2 expression was significantly upregulated, and miR-1199-5p expression was significantly downregulated in hypospadias primary cells. Intervention of SRD5A2 expression can affect cell proliferation, migration, invasion, EMT, and the expression of cell cycle-related proteins. Additionally, we found that SRD5A2 is regulated by upstream miR-1199-5p and can enhance the effect of SRD5A2 on hypospadias cells. Conclusions Silencing SRD5A2 promotes cell proliferation, invasion, and migration blocks the cell cycle at the G1 phase, and simultaneously promotes EMT, cell cycle, and cell proliferation-related protein expression. The biological function of SRD5A2 in hypospadias cells is regulated by miR-1199-5p. SRD5A2 may be an effective therapeutic target for hypospadias.

Adult Hypospadias Outcomes for the Pediatric Urologist.

PURPOSE OF REVIEW: This review article will examine the current literature on hypospadias-related complications in adult patients. RECENT FINDINGS: In this article, we will review the most recent studies evaluating hypospadias-related stricture disease, erectile function, fertility, and psychosexual outcomes in adult men with history of hypospadias repair in childhood. Managing hypospadias-related complications in adult patients is challenging to reconstructive urologists due to the compounded complexity of innate tissue deficiency and history of prior surgical repairs. In this review, we explore overall functional outcomes of adults with history of hypospadias repair as well as repair strategies of hypospadias-related urethral stricture disease. We will review erectile function, fertility and psychosexual outcomes as well as potential complications, which often do not surface until late adolescence and adulthood. Although it is challenging to characterize and quantify hypospadias-related complications, further longitudinal study is needed to better care for this complex patient population.

Comparative study of modified Koyanagi and staged Duckett for proximal hypospadias.

AIM: To compare and analyze the clinical efficacy of modified Koyanagi and staged Duckett for proximal hypospadias. METHOD: The clinical and prognostic data of children were treated and underwent surgery (modified Koyanagi or stage Duckett) in the Department of Urology, Kunming Children's Hospital from January 2020 to January 2023 were retrospectively analyzed. According to different surgical methods, the subjects were divided into the modified Koyanagi group and the staged Duckett group. Patients in both groups were followed up for more than 6 months after surgery. The success rate and complications of postoperative surgery in both groups were analyzed. RESULT: A total of 63 patients were included in this study, 34 in the modified Koyanagi group and 29 in the staged Duckett group. A total of 14 patients in the modified Koyanagi group experienced postoperative complications, the success rate of the surgery was 58.82%, and 5 among them experienced more than two kinds of complications. A total of 5 children in the staging Duckett group experienced postoperative complications, and the success rate of the operation was 82.75%. There were significant differences in the incidence of overall complications and fistula between the two surgical methods (P = 0.028). CONCLUSION: Compare with modified Koyanagi, staged Duckett can significantly reduce the incidence of overall complications and urethral fistula in patients, and have obvious advantages in the treatment of proximal hypospadias.

Comparison of outcome of TIP urethroplasty with or without Buck's Fascia repair.

OBJECTIVE: TIP is the most common preformed type of Urethroplasty. The intermediate barrier is used as a waterproofing layer to prevent fistula formation. Many tissues have been utilized as a barrier layer, with varying success rates. The search for a better intermediate layer will continue. In this study, we aim to evaluate the role of Buck's Fascia as a covering for the neo-urethra to prevent fistula formation in patients who underwent Snodgrass Urethroplasty. METHODS: This prospective study was conducted between 2018 and 2022. Patients were randomly assigned to either Group 'A' or Group 'B'. Group A included patients who underwent the Snodgrass procedure with a Buck's Fascia cover, while Group B included patients whose neo-urethra was covered with the dartos flap. These patients were closely monitored for the development of short- and long-term complications in both groups, and the results were recorded. RESULTS: The study involved 164 patients, who underwent midpenile and distal hypospadias repair using the Snodgrass technique. In Group 'A' (84 patients), the neo-urethra was covered with Buck's Fascia, while in Group 'B' (80 patients), the neo-urethra was covered with the dartos flap. The mean age of the children was (23.06 ± 16.12) months in group 'A' & (26.06 ± 14.07) months in group 'B'. mean operating time was (40 ± 11.43) minutes, in Group 'A', and (70 ± 17.43) minutes, in Group 'B'. Meatal stenosis occurred in 3.57% of children in Group 'A' and 10% of patients in Group 'B'. Urethral fistulas were encountered in 2.35% of cases in Group 'A'and 10% in Group 'B'. The difference between the groups was statistically significant.

Evaluation of postoperative complications of hypospadias using high-frequency ultrasound imaging.

PURPOSE: Various complications following hypospadias surgery present distinct manifestations when examined with ultrasound. Utilizing high-frequency ultrasound, clinicians can promptly identify these complications and initiate appropriate treatment. The aim of this study is to catalogue the ultrasonographic presentations of various postoperative complications following hypospadias surgery, thereby providing a reference for ultrasonographic diagnosis. METHODS: Ultrasonic images of post-hypospadias surgery from October 1, 2015, to June 30, 2023, recorded at the Plastic Surgery Hospital of the Chinese Academy of Medical Sciences, serve as the basis for this investigation. Drawing on patient clinical diagnoses, this study compiles and selects representative ultrasound images of diverse complications. RESULTS: The study encompassed a total of 121 subjects; 26 demonstrated urethral stricture on ultrasonic images, two presented local urethral dilation, six showed intraurethral hair-like structures, 17 revealed intraurethral septum, two exhibited intraurethral fold, one had urethral calculus, one displayed urethral calcification, 12 indicated intraurethral urine accumulation, and two showed urethral diverticulum. CONCLUSION: Ultrasound examination is helpful for postoperative diagnosis following hypospadias, detecting complications such as urethral stricture, urethral hair growth, and urethral diverticulum, which can help doctors choose appropriate clinical treatment strategies.

The Emerging Role of Artificial Intelligence and Automated Platforms for the Assessment of Penile Curvature: A Scoping Review.

PURPOSE OF THE REVIEW: The estimation of penile curvature is an essential component in the assessment of both Peyronie's disease and hypospadias-associated congenital penile curvature, as the degree of curvature can significantly impact treatment decision-making. However, there is a lack of standardization in curvature assessment and current methodologies are prone to inaccuracies. With the rise of artificial intelligence (AI) in urology, new research has explored its applications in penile curvature assessment. This review aims to evaluate the current uses of AI and other automated platforms for assessing penile curvature. RECENT FINDINGS: Several novel and promising tools have been developed to estimate penile curvature, some utilizing AI-driven models and others employing automated computational models. These platforms aim to improve curvature assessment in various settings, including at-home evaluation of Peyronie's disease, in-office assessments using three-dimensional (3D) methodologies, and preoperative evaluations for hypospadias repair. In general, these new platforms produce highly accurate and reproducible angle estimates in non-clinical studies, however their effectiveness and relation to patient outcomes has had limited evaluation in clinical settings. Significant advancements have been made in the assessment and estimation of penile curvature in both Peyronie's and pediatric patients, largely driven by AI and other automated platforms. Continued research is needed to validate these findings in clinical studies, confirm their efficacy, and assess their feasibility for real-world applications.

The potentiating effect of intravenous dexamethasone upon preemptive pudendal block analgesia for hypospadias surgery in children managed with Snodgrass technique: a randomized controlled study : Dexamethasone for pain management in children.

INTRODUCTION: Evidence regarding the potentiating effects of intravenous dexamethasone on peripheral regional anesthesia in children is sparse. The objective of the current study was to investigate the potentiating effect of intravenous dexamethasone upon pudendal block during surgical correction of hypospadias using Snodgrass technique. METHODS: The study consisted of a monocentric, randomized controlled, double-blinded study. Patients were randomized to receive either intravenous dexamethasone 0.15 mg.kg- 1 (D group) or a control solution (C group). Both groups received standardized anesthesia including a preemptive pudendal block performed after the induction of anesthesia. The primary outcome was the proportion of patients needing rescue analgesia. Secondary outcomes were other pain outcomes over the first 24 postoperative hours. RESULTS: Overall, 70 patients were included in the study. Age were 24 [24; 36] and 26 [24; 38] months in the D and C groups, respectively (p = 0.4). Durations of surgery were similar in both groups (60 [30; 60], p = 1). The proportion of patients requiring rescue analgesia was decreased in the D group (23% versus 49%, in D and C groups respectively, p = 0.02). The first administration of rescue analgesia was significantly delayed in the D group. Postoperative pain was improved in the D group between 6 and 24 h after surgery. Opioid requirements and the incidence of vomiting did not significantly differ between groups. CONCLUSION: Associating intravenous dexamethasone (0.15 mg.kg- 1) to pudendal block during hypospadias surgery improves pain control over the first postoperative day. Further studies are needed in order to confirm these results. GOV IDENTIFIER: NCT03902249. A. WHAT IS ALREADY KNOWN: dexamethasone has been found to potentiate analgesia obtained with regional anesthesia in children. B. WHAT THIS ARTICLE ADDS: intravenous dexamethasone was found to improve analgesia with a preemptive pudendal block during hypospadias surgery. C. IMPLICATIONS FOR TRANSLATION: results of this study indicate that intravenous dexamethasone could be used as an adjunct to pudendal block.

The long-term consequences of the hypospadias salvage repair issue.

PURPOSE: To present the long-term results of redo-hypospadias at our tertiary referral center following a failed prior repair. METHODS: One hundred sixty-four individuals with a history of unsuccessful repairs qualified for our retrospective cohort study. Our inclusion criteria were as follows: pre-operative data that was accessible, redo-hypospadias that was successfully repaired, and at least three years of follow-up at the last hospital visit. RESULTS: The mean patient age was 91.3 ± 21.1 months. The mean follow-up after successful repair was 41.3 ± 3.1 months. Ninety-two (group A) had one prior repair, and 72 (group B) had 2 or 3 repairs. Group A underwent six primary techniques: 32 underwent Onlay Island Flap (OIF), 10 underwent Mathieu, 12 underwent Tubularized Incised Plate Urethroplasty (TIPU), 8 underwent Urethral Mobilization (UM), and 34 underwent Buccal Mucosal Graft (BMG) { dorsal inlay Graft Urethroplasty (DIGU) in 4 and staged BMG in 30 patients}. In group B, four procedures were used: TIPU in 4, UM in 6, and BMG in 62 (staged BMG in 50 cases and DIGU in 12). CONCLUSIONS: The selected type of repair will depend on many factors, like residual healthy local skin and expertise. Safe techniques for repair of redo hypospadias after its 1st failure include TIPU, Mathieu, UM, OIF, and DIGU for distal varieties. After 2nd or 3rd repair DIGU, UM, and TIPU can be performed in distal types, while staged BMG can be applied for proximal ones.

Intravenous dexamethasone does not prolong the duration of pudendal nerve block in infants and children undergoing hypospadias surgery: A randomized clinical trial.

BACKGROUND: The administration of intravenous dexamethasone increases the duration of neuraxial block and improves the quality of analgesia. However, little is known about these effects of dexamethasone on peripheral nerve blocks in children. AIMS: In this study, we aimed to investigate the benefit of intravenous dexamethasone for enhancing the effect of pudendal block on postoperative analgesia in children who underwent hypospadias surgery. METHODS: In total, 46 children aged 6-36 months who underwent hypospadias surgery were randomly allocated to either a control group (normal saline, group C) or dexamethasone group (0.5 mg/kg, group D). Pudendal block was performed before the surgery using 0.3 mL/kg of 0.225% ropivacaine on both sides. Parents were instructed to press the patient-controlled analgesia bolus button when their children's pain score was >4 points. The primary outcome measure was the time at which the first patient-controlled analgesia by proxy bolus dose was administered. The secondary outcome measures were pain score, number of patient-controlled analgesia administration by proxy bolus attempts, number of rescue analgesics required, total amount of fentanyl administered, and overall parental satisfaction. RESULTS: The time of first patient-controlled analgesia bolus administration by proxy was not different between the control and dexamethasone groups (5.6 [5.2, 8.8] h versus 6.5 [5.4, 8.1] h, hazard ratio 0.8, 95% confidence intervals 0.43 to 1.47, p = .46). There were no statistically significant differences among the secondary outcomes. CONCLUSIONS: Administration of intravenous dexamethasone did not enhance the duration of pudendal nerve block in infants and children aged 6-36 months who underwent hypospadias surgery.

Maternal Diabetes and Risk of Hypospadias: A Systemic Review and Meta-Analysis.

INTRODUCTION: This study aimed to investigate the association between maternal diabetes and the risk of hypospadias in male infants, as the relationship between them remains uncertain. METHODS: To comprehensively evaluate the association between pregestational diabetes mellitus and gestational diabetes mellitus with hypospadias, we conducted a systematic review and meta-analysis. A thorough literature search was conducted, encompassing relevant publications published prior to January 2023. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Our meta-analysis comprised a total of 13 studies, 11 of which investigated the relationship between pregestational diabetes mellitus and hypospadias, while 9 studies explored the association between gestational diabetes mellitus and hypospadias. Notably, these investigations yielded compelling evidence of significant positive associations between pregestational diabetes mellitus and hypospadias (OR = 1.51, 95% CI = 1.13-2.03), as well as between gestational diabetes mellitus and hypospadias (OR = 1.18, 95% CI = 1.04-1.35). CONCLUSION: Our findings suggest that both pregestational diabetes mellitus and gestational diabetes mellitus are associated with an increased risk of hypospadias in offspring. Further investigations are needed to explore the optimal range of blood glucose during pregnancy that minimizes the risk of congenital malformation in the fetus, as well as to develop more effective measures for glycemic control in pregnant women.