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1.
Transl Androl Urol ; 13(8): 1364-1371, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39280686

RESUMEN

Background: Hypospadias is one of the most common congenital malformations in men. The transverse preputial island urethroplasty is widely used in China, especially for moderate and severe cases due to its convenient prepuce of the penis. This analysis aims to delineate the time to first complication following transverse preputial island urethroplasty. Methods: We analyzed the clinical data and follow-up results of children who underwent hypospadias repair by transverse preputial island urethroplasty in Beijing Children's Hospital, Capital Medical University from December 2018 to December 2019 retrospectively. Postoperative complications included urethral fistula, urethral diverticulum, urethral stricture, persistent chordee. Univariate analysis of clinical variables and time to complication was performed using Kaplan-Meier survival curve. Results: One hundred and sixty-five patients were identified. During the follow-up period, complications occurred in 101 cases (61.2%). Ninety-four percent of complications occurred within 1 year. Among children who experienced complications, Kaplan-Meier survival analysis showed that age less than 18 months and the severity of hypospadias were statistically significant (P=0.005 and P=0.04, respectively). The time to urethral diverticulum was significantly longer than that of urethral fistula and urethral stricture. Conclusions: More than 90% of complications after the transverse preputial island urethroplasty of hypospadias occurred within 1 year, with those related to proximal hypospadias presenting earlier than those of midshaft/distal hypospadias. Surgeons may consider a more frequent follow-up within the first year after surgery to detect these complications as early as possible.

2.
Balkan J Med Genet ; 27(1): 21-29, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39263642

RESUMEN

In this study, we aimed to investigate the levels of Fibroblast Growth Factor-8 (FGF-8), FGF-10, FGF-Receptor-2 (FGFR-2), Androgen receptor (AR), Estrogen receptor alpha and beta (ER-α and ER-ß) in the foreskins of children with and without hypospadias. Methods: Samples from the foreskins of 20 children with hypospadias and 20 skin samples from children without hypospadias between the ages of 14 months and 12 years were taken during circumcision or hypospadias correction surgery for immunohistochemical (IHC) examination of these markers. In IHC examination, it was shown that ER-α, ER-ß and AR receptors were more involved in the foreskin of children with hypospadias than in the fore-skin of without hypospadias children, and FGF-8, FGF-10 and FGFR-2 were lower (p<0.05). ER and AR uptake were higher in hypospadias tissue samples and FGF-8, FGF-10, and FGFR-2 uptakes were lower compared to without hypospadias children's tissue samples, and these factors were supported by affecting each other in the development of hypospadias. The limited number of studies on this subject in the literature and the contradictory results of the findings indicate that more research should be done on this subject in the future.

3.
Front Pediatr ; 12: 1459561, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39268362

RESUMEN

Objectives: There is a lack of in-depth studies on men's personal experiences of having hypospadias across different aspects of their lives. We therefore aimed to explore the experience of having hypospadias in relation to identity and interpersonal relationships. Subjects and methods: Using purposive sampling, we included 17 adult men aged 20-49 with variation in hypospadias phenotype. The informants further represented variation in sexuality, relationship status, parental status, and familial cultural context. In-depth interviews were conducted with each informant and the data was analysed using qualitative content analysis. Results: We identified four categories. Firstly, The internal experience of hypospadias in relation to being different, being impacted, and being masculine. The remaining three categories related to interpersonal spaces: Intimate spaces, comprising personal relationship with sex, having sex, and being in a relationship; Familial spaces, comprising being a son, and becoming a father; and Public spaces, comprising being hidden, being naked, and peeing. We identified the latent theme varying impact and coping, highlighting differences in experiences relating to both the internal and interpersonal. Discussion: Issues related to hypospadias included struggles with identity and confidence, as well as recurring patterns of social and sexual avoidance. While informants generally related to certain shared experiences, there is large variation in how much hypospadias impacts life, ranging from hardly at all to extensively. This could also fluctuate over time, with puberty and adolescence being an especially sensitive period. Functional and aesthetic outcomes are potentially important for well-being, especially in the case of more severe complications, while personal and interpersonal circumstances play a role in coping and the overall experience of the individual. Conclusion: Healthcare, research, and other channels such as patient groups may be able to offer support to those who need it to help more boys and men with hypospadias live unhindered lives.

4.
Investig Clin Urol ; 65(5): 487-493, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39249922

RESUMEN

PURPOSE: We aimed to identify the genetic causes of hypospadias in children using targeted gene panel sequencing for disorders of sex development (DSD). MATERIALS AND METHODS: This study included 18 twin boys with hypospadias: seven and two pairs were monozygotic and dizygotic twins, respectively, and six were discordant and three were concordant twins. Targeted gene panel sequencing for 67 known DSD genes was performed. Sequence variants were classified into five different categories, pathogenic, likely pathogenic, variants of uncertain significance, likely benign, and benign, following the American College of Medical Genetics and Genomics Standards and Guidelines. RESULTS: The mean gestational age and birth weight were 35.3±2.0 weeks and 1.96±0.61 kg, respectively, with seven patients being small for gestational age. Hypospadias was present in 12 patients, with posterior type in 33.3% and anterior type in 66.7%. In three families with twins, both siblings had hypospadias. In addition, cryptorchidism was observed in one subject. Surgical correction of hypospadias was performed at a mean age of 22.1 months. Molecular analysis identified 12 different genetic variants, including two pathogenic mutations in the AMH (p.E389*) and SRD5A2 (p.R246Q) genes, found in subjects with hypospadias, respectively. However, only heterozygous mutations were detected. CONCLUSIONS: This study did not identify a definitive genetic component contributing to the development of hypospadias; however, the findings suggest that intrauterine growth retardation may play a significant role.


Asunto(s)
Hipospadias , Gemelos Monocigóticos , Humanos , Masculino , Hipospadias/genética , Hipospadias/cirugía , Gemelos Monocigóticos/genética , Enfermedades en Gemelos/genética , Lactante , Recién Nacido , Mutación
5.
BJU Int ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39224939

RESUMEN

OBJECTIVE: To assess the cumulative rates of re-operations after hypospadias repair and evaluate long-term surgical outcomes at a tertiary paediatric urology centre. PATIENTS AND METHODS: Retrospective analysis of 293 boys born between 1991 and 2003 undergoing hypospadias surgery was conducted. The study included 274 patients: 165 with distal, 34 with midshaft, and 75 with proximal hypospadias. Kaplan-Meier methods were used to evaluate the re-operation data. RESULTS: The median age at primary surgery was 1.3 years, with a median follow-up of 14.4 years. The overall re-operation rate was 48.2%, with approximately half of the problems detected within the first 3 months after surgery. The risk of re-operation was correlated with hypospadias severity, with 5- and 15-year re-operation risks at 39.3% and 51.8%, respectively. Limitations of the study include its retrospective nature and variations in surgical techniques from current standards. CONCLUSION: There is a significant risk of unplanned re-operations following hypospadias repair, increasing with the severity of the original condition. This underscores the need for extended follow-up and effective communication with patients and their families about the likelihood of requiring multiple surgeries for optimal outcomes.

6.
Int J Urol ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39231782

RESUMEN

PURPOSE: The concept of interposing double dorsal preputial flaps to cover the urethroplasty was introduced in 2005 to reduce the risk of urethrocutaneous fistula (UCF). Our study aims to compare the postoperative outcomes of urethroplasty for distal hypospadias between two groups: one receiving single preputial flap coverage and another receiving double flap coverage. MATERIALS AND METHODS: We conducted a retrospective analysis study of boys with primary distal hypospadias who underwent surgery by the same experienced surgeon, at our department between 2010 and 2021. The study population was divided into two groups: Group A, which underwent urethroplasty coverage with single dorsal preputial flap, and Group B, which underwent coverage with double flap. Postoperative complications were compared between the two groups. RESULTS: We collected 105 cases, comprising 51 in Group A and 54 cases in Group B. The mean age at surgery was 29 months in Group A and 24 months in Group B. Post-operative follow-up period ranged from 6 months to 8 years. Functional and cosmetic outcomes were judged excellent in 88.7%. Only 10 boys experienced complications requiring reoperation. UCF occurred in 5 patients from Group A, while no cases were reported in Group B (p = 0.024). Meatal stenosis was identified in three patients in Group A and in two patients in Group B (p = 1). No other complications, such as glans dehiscence or penile torsion, were noted. CONCLUSION: Double dorsal dartos flap is an effective method for covering the new urethra and can be recommended in the treatment of patients with virgin distal hypospadias.

7.
JFMS Open Rep ; 10(2): 20551169241272195, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39224536

RESUMEN

Case summary: An 11-year-old neutered male Turkish Angora cat was referred for obstructive feline lower urinary tract disease (FLUTD). On physical examination, the penis was curved at the tip and had a smaller than normal urethral opening proximal to the end, consistent with singular glandular hypospadias with a dorsal penile curvature. Because of its recurrent obstructive FLUTD history and inability to catheterise the urethra, a preputial urethrostomy (PRU) was performed. The PRU resolved the clinical signs with no clinical recurrence and no short- or long-term complications. Relevance and novel information: To the authors' knowledge, this is the first description of singular glandular hypospadias in a cat. In addition, this is the first time feline hypospadias has been reported to occur with obstructive FLUTD and to be treated by preputial urethrostomy.

8.
Ecotoxicol Environ Saf ; 284: 116988, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39236653

RESUMEN

Hypospadias is one of the most common congenital anomalies of the male urogenital system, and di(2-ethylhexyl) phthalate (DEHP), a widely used endocrine-disrupting chemical (EDC), is considered a significant risk factor for this condition. Mono-2-ethylhexyl phthalate (MEHP), the toxic active metabolite of DEHP, has been proven to affect penile development and ultimately result in the hypospadias phenotype. However, while it is acknowledged that hypospadias arises from the aberrant development of multiple penile tissues, the specific impact of MEHP on human foreskin tissue development and its underlying molecular mechanisms of action remain unclear. In this study, we constructed an in vitro toxicity assay for MEHP using human foreskin fibroblasts and employed high-throughput RNA sequencing to investigate the molecular mechanisms subserving the defects in cellular function. We subsequently conducted multi-omics data analysis using public databases to analyze key target genes, and identified MMP11 as a chief downstream gene responsible for the effects of MEHP on HFF-1 cell migration. Through molecular docking analysis and molecular biology experiments, we further demonstrated that the nuclear receptor PPAR-gamma was activated upon binding with MEHP, leading to the suppression of MMP11 expression. Additionally, we found that epigenetic modifications induced by MEHP were also involved in its pathogenic effects on hypospadias. Our research highlights the crucial role of impaired cellular proliferation and migration in MEHP-induced hypospadias. We identified the MEHP/PPAR-gamma/MMP11 pathway as a novel pathogenic mechanism, providing important potential targets for future preventive strategies with respect to hypospadias.

9.
Cureus ; 16(7): e63766, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39100022

RESUMEN

Background  Congenital anomalies of the kidney and urinary tract (CAKUT) encompass a diverse array of disorders arising from developmental irregularities in the renal parenchymal development, disrupted embryonic migration of the kidneys, and the urinary collecting system. This study aimed to investigate the clinical presentations, patterns of obstructive and non-obstructive CAKUT, and associated extrarenal manifestations in affected children. Methods This observational study was conducted in the Department of Pediatrics, Acharya Vinoba Bhave Rural Hospital, Wardha. Ethical clearance was obtained, and the study included 105 diagnosed CAKUT patients aged from birth to 18 years. Data collection spanned from June 2022 to May 2024. Clinical features, antenatal findings, associated anomalies, estimated glomerular filtration rate (eGFR), and serum creatinine levels were recorded. Descriptive and inferential statistical analyses were performed using Stata software. Results Among the 105 participants, 81 (77.14%) were males, with a male-to-female ratio of 3.37:1. The mean age was 42.49 months. Forty-two individuals (40%) were asymptomatic, while the most common symptomatic presentation was the ventral opening of the urethra (24.76%). Extrarenal malformations were present in 35 subjects (33.33%), with undescended testis (25.71%) and congenital heart disease (CHD) (20%) being the most common. The antenatal diagnosis was made in 63.8% of cases. Obstructive uropathy was present in 42.86% of subjects, with a significant association between antenatal diagnosis and bilateral hydronephrosis. Medical management was provided to 41.9% of subjects, while 58.1% underwent surgical interventions. Conclusion The study highlights the clinical variability and diverse presentations of CAKUT in children, with a substantial proportion being asymptomatic. Early detection through antenatal screening and prompt intervention can potentially prevent or delay the progression to ESRD. The findings underscore the importance of comprehensive evaluation and targeted management strategies to address both renal and extrarenal manifestations of CAKUT.

10.
Urologia ; : 3915603241273616, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39171667

RESUMEN

INTRODUCTION: Distal hypospadias accounts for the majority of hypospadias. Mathieu and Snodgrass techniques are widely used for repair of distal hypospadias but their comparative efficacy and reported outcomes are still debated. We conducted a systematic review and meta-analysis to compare the outcomes of these two techniques. METHODS: Electronic databases and trial registries were searched for randomized controlled trials (RCTs) comparing Mathieu and Snodgrass techniques for primary distal hypospadias repair. Outcome measures included complication rates and cosmetic outcomes. Risk of bias assessment was performed using the ROB2. Data was analyzed using Review Manager 5.4; Trial Sequential Analysis (TSA) also was conducted for important outcomes. RESULTS: Twelve RCTs were eligible for inclusion. The Snodgrass technique showed a significantly lower incidence of urethrocutaneous fistula (UCF) (RR 0.48, 95% CI [0.30-0.77]). However, there was no significant difference in the incidence of meatal stenosis (MS) between the two (RR 1.64, 95% CI [0.85-3.15]). TSA supports the findings for outcome UCF but not for MS. Operative time was shorter with the Snodgrass technique. CONCLUSION: This SRMA indicates a lower incidence of UCF with Snodgrass technique compared to the Mathieu technique in distal hypospadias repair. However, there was no significant difference in the risk of MS.

11.
Indian J Anaesth ; 68(8): 725-730, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39176123

RESUMEN

Background and Aims: Caudal block is more frequently used in children for postoperative analgesia. However, its disadvantage is its short duration. Erector spinae plane block (ESPB) at the sacral level can potentially block the pudendal nerve. It may prove an alternative to caudal block for hypospadias repair regarding time to first rescue analgesia. Methods: Fifty children of 2-7 years of age were included. After induction of general anaesthesia, Group I (n = 25) was given ultrasound-guided sacral ESPB with 1 ml/kg of 0.25% bupivacaine and Group II (n = 25) was given caudal block with 0.5 ml/kg of 0.25% bupivacaine. Postoperatively at face, leg, activity, cry, consolability (FLACC) score ≥4, rescue analgesia was given using intravenous 15 mg/kg paracetamol. The primary outcome was to compare time to first rescue analgesia, and secondary outcomes were intraoperative haemodynamic parameters, fentanyl consumption, postoperative FLACC score and analgesic consumption in 24 h. Continuous variables were compared using the independent sample t-test or Mann-Whitney test, and categorical variables were compared using the Chi-square test. Results: The mean time to first rescue analgesia was 21.30 (standard deviation [SD]: 3.06) h in Group I and 9.36 (SD: 1.71) h in Group II (P < 0.001) (mean difference -11.94 [95% CI: -13.39, -10.48]). The FLACC score was significantly higher (P < 0.05) postoperatively at 8, 10, 12 and 18 h in Group II. Mean postoperative analgesic consumption was 310.5 (SD: 72.69) mg in Group I and 615.6 (SD: 137.51) mg in Group II (P < 0.001) (mean difference 30.5 [95% CI: 236.41, 373.78]). Conclusion: Sacral ESPB is better regarding time to first rescue analgesia than caudal block in paediatric patients undergoing hypospadias repair.

12.
Pediatr Surg Int ; 40(1): 233, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39158792

RESUMEN

PURPOSE: This study evaluates the inter-rater agreements of both the Glans-Urethral Meatus-Shaft (GMS) hypospadias score and Hypospadias Objective Penile Evaluation (HOPE) score, aiming to standardize disease classification for consistent agreement in clinically relevant characteristics of hypospadias. METHODS: Photos of hypospadias in children were collected from two separate institutions. Three raters scored the photos using GMS and HOPE, excluding penile torsion and curvature assessment in HOPE due to photo limitations. RESULTS: A total of 528 photos were included. With GMS, Fleiss' multi-rater kappa showed an agreement of 0.745 for glans-urethral plate, 0.869 for meatus, and 0.745 for shaft. For HOPE scores, the agreements were 0.888 for position of meatus, 0.669 for shape of meatus, 0.730 for shape of glans, and 0.708 for the shape of the skin. The lower agreement in the shape of the meatus evaluation may be attributed to the lack of a quantitative classification method in HOPE. Experts rely on their subjective judgment based on the provided example photos and their index patient. CONCLUSIONS: While there is high agreement among experts when evaluating hypospadias using the GMS and HOPE scoring criteria, only the position of the meatus achieved nearly perfect agreement highlighting that the current scoring systems entail a subjective element in disease classification.


Asunto(s)
Hipospadias , Pene , Uretra , Humanos , Hipospadias/clasificación , Masculino , Lactante , Fotograbar/métodos , Preescolar , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Niño
13.
J Pediatr Urol ; 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39153923

RESUMEN

INTRODUCTION/BACKGROUND: Patient-reported outcome measures (PROMs) for hypospadias care are lacking, and most existing instruments were developed without patient input. OBJECTIVE: The objective of this study was to 1) use our previously developed Hypospadias Journal for concept elicitation in a sample of adolescent and young adult hypospadias patients and 2) develop a new hypospadias PROM. STUDY DESIGN: We recruited English-speaking males ages 13-30 living in the United States with a self-reported history of hypospadias through targeted advertisements on Facebook and Instagram from March to June 2022. Using a Qualtrics screening survey ineligible respondents were identified using automated fraud detection and manual review. Consenting participants were sent an electronic Hypospadias Journal containing brief creative writing exercises and multiple-choice scales to facilitate participant reflections about genital appearance, urination, sexual function, and psychosocial well-being. Demographics were summarized using descriptive statistics. Human-centered design researchers synthesized the journals' key themes to 1) create an affinity diagram with hypospadias-related quality of life (QOL) domains and 2) draft items for the PROM covering each domain and sub-domain. Journal participants were asked to complete a survey to 1) rank hypospadias QOL domains, subdomains, and draft items for the PROM, and 2) explore their preferences for item phrasing. In a small group virtual interview, a urologist and a hypospadias patient reviewed and revised draft PROM items, and a final PROM was created. RESULTS: Of the 411 completed screening surveys, 391 were ineligible. Journals were sent to 20 eligible participants. Of these, 12 completed journals: 8 adults; 4 adolescents (11 surgical/1 non-surgical): 66.7% White, 8.3% Black, 16.7% Asian, 8.3% >1 race. The meatal location was distal for 41.7%, proximal for 41.7%, unknown/missing for 16.7%. We identified four hypospadias-related quality-of-life domains and 13 respective sub-domains (Extended Summary Figure) of these, two were novel domains: 1) knowledge about the condition/treatment and comfort with treatment decision, and 2) impact on relationships with caregivers, medical providers, and sexual partners. A final PROM prototype, the Patient Assessment Tool for Hypospadias (PATH) was created, covering all QOL domains identified by participants. DISCUSSION: We created a simple, brief hypospadias PROM to screen for salient topics to be addressed by providers in the clinical setting. Limitations include the small sample size and limited clinical details about participants. CONCLUSIONS: Our study provides a hypospadias PROM that is ready for psychometric assessment in a larger sample.

14.
J Indian Assoc Pediatr Surg ; 29(4): 340-344, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39149434

RESUMEN

Purpose: To compare the accuracy of unaided visual inspection (UVI) to Software App measurement (SAM) of penile curvature (PC) during hypospadias surgery. Methods: Seven clinical pictures of PC (15°-60°) taken during hypospadias repair were shared with 300 members of the Society of Pediatric Urology (India). The respondents were asked to assess the angles by UVI and indicate their preferred correction method of that PC. For each picture, the angles of curvature estimated by UVI were compared with the objective angle measured using an app (SAM), which was considered an accurate estimation. Statistical analysis was done using software; P<0.05 was considered as statistically significant. Results: Ninety-one of 101 (90%) respondents preferred UVI to measure PC during hypospadias surgery. For 6/7 pictures, <40% of participants estimated the angle correctly by UVI (P < 0.001), with the difference in estimation being 3.6°-14.9°. For pictures with PC >30°, the error in UVI estimation was >10°, with no correlation between the accuracy of UVI estimate and surgeon experience. A significant proportion of surgeons chose the incorrect option for PC correction, which was the lowest (69%) for PC 35.8°. Conclusions: Most surgeons preferred UVI to assess PC; UVI is an erroneous technique to measure PC angle, especially in the PC range 30°-60°, where the error was >10°. Most errors were an underestimation of the PC, irrespective of surgeon experience. There was a significant error in the choice of technique for PC correction for a PC of 35°. These results strongly support the objective assessment of PC using SAM during hypospadias repair.

15.
Children (Basel) ; 11(8)2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39201906

RESUMEN

Platelet-Rich Plasma (PRP) therapy has become a promising treatment option in pediatric surgery, offering a novel approach to tissue repair and regeneration. Obtained from the patient's own blood or umbilical cord blood (CB), PRP is a concentrated form of plasma enriched with platelets, growth factors, and cytokines essential for stimulating tissue healing. This systematic review explores the applications of PRP therapy in pediatric surgical procedures, focusing on its role in promoting wound healing, reducing postoperative complications, and enhancing patient outcomes. A systematic literature overview was conducted in accordance with PRISMA guidelines, encompassing studies published between 2004 and 2024. The research has identified different fields of application for PRP therapy in pediatric surgery, including treatment of pilonidal sinus and hypospadias repair. Key findings from clinical studies and randomized controlled trials are summarized, highlighting the efficacy of PRP therapy in accelerating wound healing, reducing pain, and improving patient recovery. Despite promising results, challenges and controversies surrounding PRP therapy persist, including variability in preparation protocols and optimal dosing regimens. The safety of PRP therapy in pediatric patients is also discussed, emphasizing its autologous nature and minimal risk of adverse reactions. In summary, this review highlights the role of PRP therapy as a safe and effective therapeutic approach in pediatric surgery, while further research to standardize protocols and elucidate optimal treatment strategies are still necessary.

16.
J Pediatr Urol ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39214745

RESUMEN

INTRODUCTION: Previous studies have suggested that hypertensive disorders of pregnancy increase risk of hypospadias, but so far none have focused on the influence of maternal chronic hypertension (CH). This study aimed to conduct a systematic review and meta-analysis of currently available observational data to assess the association of maternal CH with hypospadias risk. METHODS: Literature searches were performed using EMBASE, SCOPUS, Pubmed, and manual methods according to PRISMA 2020 guidelines and MOOSE checklist. Eligible articles were included in the study and assessed for quality using the Newcastle-Ottawa Scale (NOS). Extracted data were presented in review tables. Pooled analysis for unadjusted and adjusted effect sizes was used to determine OR and 95%CI using DerSimonian and Laird model. Heterogeneity was tested using I2 test, and publication bias was examined using funnel plots. Sensitivity analyses are done to address uncertainties. RESULTS: Searches yielded a total of 1130 publications with six eligible studies and high NOS quality score (6-9) were selected as depicted in extended summary figure. There were 519 hypospadias patients with maternal CH among those six eligible studies for analysis. After sensitivity analysis, there is one study that is excluded due to different hypospadias definition. Among the 5 remaining studies, it is found that there is an elevated risk of hypospadias in the context of maternal CH as determined by pooled unadjusted and adjusted OR (OR 1.50 95%CI 1.17-1.93; aOR 1.77 95%CI 1.54-2.04 respectively). Heterogeneity was high in unadjusted pooled analysis (I2 = 73% P = 0.005) and low in adjusted analysis (I2 = 0% P = 0.40)). Funnel plots were symmetrical in both analyses indicating a lack of publication bias. CONCLUSIONS: This meta-analysis indicates that maternal CH increases risk of hypospadias in male offspring. Future studies should weigh in biological mechanisms and pharmacological effects to elaborate the pathogenesis of this association.

17.
Epigenetics ; 19(1): 2392048, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39151125

RESUMEN

In patients with proximal hypospadias, often no genetic cause is identified despite extensive genetic testing. Many genes involved in sex development encode transcription factors with strict timing and dosing of the gene products. We hypothesised that there might be recurrent differences in DNA methylation in boys with hypospadias and that these might differ between patients born small versus appropriate for gestational age. Genome-wide Methylated DNA sequencing (MeD-seq) was performed on 32bp LpnPI restriction enzyme fragments after RE-digestion in leucocytes from 16 XY boys with unexplained proximal hypospadias, one with an unexplained XX testicular disorder/difference of sex development (DSD) and twelve, healthy, sex- and age-matched controls. Five of seven differentially methylated regions (DMRs) between patients and XY controls were in the Long Intergenic Non-Protein Coding RNA 665 (LINC00665; CpG24525). Three patients showed hypermethylation of MAP3K1. Finally, no DMRs in XX testicular DSD associated genes were identified in the XX boy versus XX controls. In conclusion, we observed no recognizable epigenetic signature in 16 boys with XY proximal hypospadias and no difference between children born small versus appropriate for gestational age. Comparison to previous methylation studies in individuals with hypospadias did not show consistent findings, possibly due to the use of different inclusion criteria, tissues and methods.


Asunto(s)
Metilación de ADN , Hipospadias , Humanos , Masculino , Hipospadias/genética , Proyectos Piloto , Epigénesis Genética , Islas de CpG , ARN Largo no Codificante/genética , Niño , Preescolar , Lactante , Estudio de Asociación del Genoma Completo , Estudios de Casos y Controles
18.
BMC Med Genomics ; 17(1): 195, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39103808

RESUMEN

BACKGROUND: The Cut Homeobox 1 (CUX1) gene has been implicated in a number of developmental processes and has recently emerged as an important cause of developmental delay and impaired intellectual development. Individuals with variants in CUX1 have been described with a variety of co-morbidities including variations in sex development (VSD) although these features have not been closely documented. CASE PRESENTATION: The proband is a 14-year-old male who presented with congenital complex hypospadias, neurodevelopmental differences, and subtle dysmorphism. A family history of neurodevelopmental differences and VSD was noted. Microarray testing and whole exome sequencing found the 46,XY proband had a large heterozygous in-frame deletion of exons 4-10 of the CUX1 gene. CONCLUSIONS: Our review of the literature has revealed that variants in CUX1 are associated with a range of VSD and suggest this gene should be considered in cases where a VSD is noted at birth, especially if there is a familial history of VSD and/or neurodevelopmental differences. Further work is required to fully investigate the role and regulation of CUX1 in sex development.


Asunto(s)
Proteínas de Homeodominio , Proteínas Represoras , Humanos , Masculino , Proteínas de Homeodominio/genética , Adolescente , Proteínas Represoras/genética , Factores de Transcripción/genética , Desarrollo Sexual/genética
19.
World J Clin Pediatr ; 13(2): 90583, 2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38947997

RESUMEN

Apart from listening to the cry of a healthy newborn, it is the declaration by the attending paediatrician in the labour room that the child is normal which brings utmost joy to parents. The global incidence of children born with congenital anomalies has been reported to be 3%-6% with more than 90% of these occurring in low- and middle-income group countries. The exact percentages/total numbers of children requiring surgical treatment cannot be estimated for several reasons. These children are operated under several surgical disciplines, viz, paediatric-, plastic reconstructive, neuro-, cardiothoracic-, orthopaedic surgery etc. These conditions may be life-threatening, e.g., trachea-oesophageal fistula, critical pulmonary stenosis, etc. and require immediate surgical intervention. Some, e.g., hydrocephalus, may need intervention as soon as the patient is fit for surgery. Some, e.g., patent ductus arteriosus need 'wait and watch' policy up to a certain age in the hope of spontaneous recovery. Another extremely important category is that of patients where the operative intervention is done based on their age. Almost all the congenital anomalies coming under care of a plastic surgeon are operated as elective surgery (many as multiple stages of correction) at appropriate ages. There are advantages and disadvantages of intervention at different ages. In this article, we present a review of optimal timings, along with reasoning, for surgery of many of the common congenital anomalies which are treated by plastic surgeons. Obstetricians, paediatricians and general practitioners/family physicians, who most often are the first ones to come across such children, must know to guide the parents appropriately and convincingly impress upon the them as to why their child should not be operated immediately and also the consequences of too soon or too late.

20.
J Pediatr Urol ; 20(4): 692.e1-692.e6, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38951046

RESUMEN

BACKGROUND: Urethrocutaneous fistula (UCF) formation is a known complication following hypospadias repair, affecting between 5 and 70% of cases. Moreover, approximately 30% of patients experience refistulization after UCF repair. The use of extracellular matrices, such as AmnioCord, a dehydrated human umbilical cord allograft manufactured by MiMedx®, may mitigate high rates of refistulization. OBJECTIVE: To determine whether the use of AmnioCord during UCF repair is associated with reduced incidence of subsequent UCFs among pediatric patients. DESIGN, SETTING, AND PARTICIPANTS: Electronic medical records were retrospectively reviewed among 60 patients who underwent at least one UCF repair at a pediatric hospital in a large urban setting in the U.S. between January 2012-June 2018. Patients were followed through January 2024. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Adjusted generalized estimating equation regression models were used to assess the association between AmnioCord use and rates of refistulization, while controlling for confounding variables. RESULTS: The number of fistula presentations per patient ranged from one to four; 53.3% had one fistula, 30.0% had two, and 16.6% had three or more. Overall fistula repair success rate was 56.8% but significantly differed by AmnioCord use in adjusted modelling; 69.4% of cases that received AmnioCord were successfully repaired, compared to 47.2% of cases that did not receive AmnioCord. In adjusted models, patients who received AmnioCord had 2.66 times greater odds of surgical success than patients who did not receive AmnioCord (95% CI:1.13-6.24; p = 0.02). CONCLUSIONS: This study demonstrates a positive association between AmnioCord use and successful UCF closure among pediatric patients.


Asunto(s)
Fístula Cutánea , Hipospadias , Complicaciones Posoperatorias , Cordón Umbilical , Enfermedades Uretrales , Fístula Urinaria , Humanos , Masculino , Estudios Retrospectivos , Fístula Urinaria/etiología , Fístula Urinaria/cirugía , Fístula Urinaria/epidemiología , Fístula Cutánea/etiología , Fístula Cutánea/cirugía , Fístula Cutánea/epidemiología , Preescolar , Hipospadias/cirugía , Enfermedades Uretrales/cirugía , Enfermedades Uretrales/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Cordón Umbilical/cirugía , Lactante , Resultado del Tratamiento , Niño , Procedimientos Quirúrgicos Urológicos Masculinos/métodos , Aloinjertos
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