RESUMO
Ovotesticular syndrome is a rare disorder of sex development characterized by the presence of testicular and ovarian tissue. The histologic characteristics of human testicular tissue are well defined by the presence of seminiferous cords or tubules containing TSPY-positive germ cells and Sox9-positive Sertoli cells surrounded by interstitial tissue containing cytochrome P450-positive Leydig cells and smooth muscle α-actin-positive peritubular myoid cells. The histological characteristics of the ovary can be defined by germ cell nests and the development of follicles. In contrast to the testis, the ovary has a paucity of defined specific protein markers, with the granulosa cell marker FOXL2 being the most widely used. In practice, defining the ovarian component of the ovotestis can be quite difficult. We developed a model of human ovotesticular syndrome by combining fetal human testis and ovary in a xenograft model. Ovotesticular xenografts were grown under the renal capsules of gonadectomized athymic nude mice for 6-32 weeks along with age matched control grafts of fetal testis and ovary. Forty ovotesticular xenografts and their controls were analyzed by histology, immunohistochemistry, and fluorescent in situ hybridization to determine the protein expression and karyotype of the cells within the grafts. The ovotesticular xenografts exhibited recognizable testicular and ovarian tissue based on testis-specific and ovary-specific markers defined above. The xenografts simulated a bipolar ovotestis in which the testicular and ovarian elements retain their separate histological characteristics and are separated by a well-defined border. This contrasts with the compartmentalized ovotestis previously described in the literature where the testicular tissue is surrounded by ovarian tissue or a mixed histology where testicular and ovarian tissues are interspersed throughout the gonad. In conclusion, we have characterized a human model of ovotestis which will allow a deeper understanding of ovotestis development in humans and facilitate a more accurate diagnosis of the ovotesticular syndrome.
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Transtornos Ovotesticulares do Desenvolvimento Sexual , Testículo , Feminino , Animais , Camundongos , Humanos , Masculino , Camundongos Nus , Hibridização in Situ Fluorescente , Gônadas , Ovário , Transtornos Ovotesticulares do Desenvolvimento Sexual/diagnóstico , Transtornos Ovotesticulares do Desenvolvimento Sexual/metabolismo , Transtornos Ovotesticulares do Desenvolvimento Sexual/patologiaRESUMO
A comprehensive immunohistochemical ontogeny of the developing human fetal testis has remained incomplete in the literature to date. We collected human fetal testes from 8 to 21 weeks of fetal age, as well as postnatal human testes at minipuberty, pre-pubertal, and pubertal stages. Immunohistochemistry was performed with a comprehensive panel of antigens targeting gonadocytes, Sertoli cells, fetal Leydig cells, peritubular myoid cells, and other hormonal and developmental targets. Testicular cords, precursor structures to seminiferous tubules, developed from 8 to 14 weeks of fetal age, separating the testis into the interstitial and intracordal compartments. Fetal gonadocytes were localized within the testicular cords and evaluated for Testis-Specific Protein Y, Octamer-binding transcription factor 4, Sal-like protein 4, and placental alkaline phosphatase expression. Fetal Sertoli cells were also localized in the testicular cords and evaluated for SRY-box Transcription Factor 9, inhibin, and anti-Mullerian hormone expression. Fetal Leydig cells were present in the interstitium and stained for cytochrome p450c17 and calretinin, while interstitial peritubular myoid cells were examined using smooth muscle α-actin staining. Androgen receptor expression was localized close to the testicular medulla at 8 weeks and then around the testicular cords in the interstitium as they matured in structure. Postnatal staining showed that Testis-Specific Protein Y remained positive of male gonadocytes throughout adulthood. Anti-Mullerian hormone, SRY-box Transcription Factor 9, and Steroidogenic factor 1 are expressed by the postnatal Sertoli cells at all ages examined. Leydig cell markers cytochrome p450c17 and calretinin are expressed during mini-puberty and puberty, but not expressed during the pre-pubertal period. Smooth muscle α-actin and androgen receptor were not expressed during mini-puberty or pre-puberty, but again expressed during the pubertal period. The ontogenic map of the human fetal and postnatal testicular structure and expression patterns described here will serve as a reference for future investigations into normal and abnormal testicular development.
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Receptores Androgênicos , Testículo , Recém-Nascido , Humanos , Masculino , Feminino , Gravidez , Adulto , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Calbindina 2/metabolismo , Hormônio Antimülleriano/metabolismo , Actinas/genética , Actinas/metabolismo , Placenta/metabolismo , Células de Sertoli , Antígenos de Diferenciação/metabolismo , Diferenciação Celular/genética , Fatores de Transcrição/metabolismo , Citocromos/metabolismoRESUMO
A definition of normal human fetal and early postnatal ovarian development is critical to the ability to accurately diagnose the presence or absence of functional ovarian tissue in clinical specimens. Through assembling an extensive histologic and immunohistochemical developmental ontogeny of human ovarian specimens from 8 weeks of gestation through 16 years of postnatal, we present a comprehensive immunohistochemical mapping of normal protein expression patterns in the early fetal through post-pubertal human ovary and detail a specific expression-based definition of the early stages of follicular development. Normal fetal and postnatal ovarian tissue is defined by the presence of follicular structures and characteristic immunohistochemical staining patterns, including granulosa cells expressing Forkhead Box Protein L2 (FOXL2). However, the current standard array of immunohistochemical markers poorly defines ovarian stromal tissue, and additional work is needed to identify new markers to advance our ability to accurately identify ovarian stromal components in gonadal specimens from patients with disorders of sexual differentiation.
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Folículo Ovariano , Ovário , Feminino , Humanos , Antígenos de Diferenciação/metabolismo , Diferenciação Celular , Células da Granulosa/metabolismo , Folículo Ovariano/crescimento & desenvolvimento , Ovário/crescimento & desenvolvimentoRESUMO
PURPOSE: Cystoscopic injection of botulinum neurotoxin (BoNT) is typically performed under general anesthesia in pediatric patients with neurogenic bladder, accumulating anesthetic exposures and operating room costs. As most of these patients already tolerate clean intermittent catheterization (CIC), it has become our practice to offer a trial of awake injection. We report our initial experience here. We hypothesized that higher sensory level, female sex and absence of mental health issues or cognitive delay might predict successful first awake injection and decreased operative times. MATERIALS AND METHODS: Surgical records from 2 academic hospitals from 2018-2020 were reviewed. Generalized linear models were fit to determine predictors of success and procedural length. RESULTS: Trial of awake injection was offered to 22 patients. Eighteen patients (8 female, 10 male, 4-20 years old) elected to proceed. All 18 patients were managed with CIC at baseline, 14 had anxiety or behavioral issues, 10 had cognitive delay and 7 had sensory level below S2. Two patients (11%) required conversion to general anesthesia and one of these subsequently opted for a repeat awake injection trial. Fifteen of the 18 patients (83%) had or planned subsequent injections awake. Of the remaining, 1 proceeded to bladder augment, 1 is considering ileovesicostomy and 1 requested subsequent injections under anesthesia. No intraoperative complications occurred. CONCLUSIONS: Awake BoNT injection is feasible in pediatric patients with neurogenic bladder managed with CIC, even in the setting of intact sensation, well-managed mental health issues or cognitive delay, thereby increasing the viability of BoNT as an early tool in the management of neurogenic bladder.
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Toxinas Botulínicas Tipo A , Fármacos Neuromusculares , Bexiga Urinaria Neurogênica , Bexiga Urinária Hiperativa , Administração Intravesical , Adolescente , Adulto , Toxinas Botulínicas Tipo A/uso terapêutico , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Humanos , Masculino , Fármacos Neuromusculares/uso terapêutico , Resultado do Tratamento , Bexiga Urinaria Neurogênica/tratamento farmacológico , Bexiga Urinária Hiperativa/tratamento farmacológico , Vigília , Adulto JovemRESUMO
The Jost hypothesis states that androgens are necessary for normal development of the male external genitalia. In this review, we explore the complementary hypothesis that estrogens can elicit abnormal development of male external genitalia. Herein, we review available data in both humans and mice on the deleterious effects of estrogen on external genitalia development, especially during the "window of susceptibility" to exogenous estrogens. The male and female developing external genitalia in both the human and mouse express ESR1 and ESR2, along with the androgen receptor (AR). Human clinical data suggests that exogenous estrogens can adversely affect normal penile and urethral development, resulting in hypospadias. Experimental mouse data also strongly supports the idea that exogenous estrogens cause penile and urethral defects. Despite key differences, estrogen-induced hypospadias in the mouse displays certain morphogenetic homologies to human hypospadias, including disruption of urethral fusion and preputial abnormalities. Timing of estrogenic exposure, or the "window of susceptibility," is an important consideration when examining malformations of the external genitalia in both humans and mice. In addition to a review of normal human and mouse external genital development, this article aims to review the present data on the role of estrogens in normal and abnormal development of the mouse and human internal and external genitalia. Based on the current literature for both species, we conclude that estrogen-dependent processes may play a role in abnormal genital development.
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Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Estrogênios/metabolismo , Genitália Masculina/crescimento & desenvolvimento , Receptores Androgênicos/genética , Animais , Estrogênios/genética , Feminino , Genitália Masculina/metabolismo , Humanos , Masculino , Camundongos , Organogênese/genética , Pênis/crescimento & desenvolvimento , Pênis/metabolismoRESUMO
To better understand how the human fetal penis and clitoris grows and remodels, we undertook an investigation to define active areas of cellular proliferation and programmed cell death spatially and temporally during development of human fetal external genitalia from the indifferent stage (8 weeks) to 18 weeks of gestation. Fifty normal human fetal penile and clitoral specimens were examined using macroscopic imaging, scanning electron microscopy and immunohistochemical localization for the cellular proliferation and apoptotic markers, Ki67 and Caspase-3. A number of hot spots of cellular proliferation characterized by Ki67 localization are present in the penis and clitoris especially early in development, most notably in the corporal body, glans, remodeling glanular urethra, the urethral plate, the roof of the urethral groove and the fully formed penile urethra. The 12-fold increase in penile length over 10 weeks of growth from 8 to 18 weeks of gestation based on Ki67 labelling appears to be driven by cellular proliferation in the corporal body and glans. Throughout all ages in both the developing penis and clitoris Ki67 labeling was consistently elevated in the ventral epidermis and ventral mesenchyme relative to the dorsal counterparts. This finding is consistent with the intense morphogenetic activity/remodeling in the ventral half of the genital tubercle in both sexes involving formation of the urethral/vestibular plates, canalization of the urethral/vestibular plates and fusion of the urethral folds to form the penile urethra. Areas of reduced or absent Ki67 staining include the urethral fold epithelium that fuses to form the penile tubular urethra. In contrast, the urethral fold mesenchyme is positive for Ki67. Apoptosis was rarely noted in the developing penis and clitoris; the only area of minimal Caspase-3 localization was in the epithelium of the ventral epithelial glanular channel remodeling.
Assuntos
Clitóris/embriologia , Clitóris/metabolismo , Morfogênese , Pênis/embriologia , Pênis/metabolismo , Receptores Androgênicos/metabolismo , Receptores de Estrogênio/metabolismo , Clitóris/ultraestrutura , Feminino , Humanos , Masculino , Microscopia Eletrônica de Varredura , Pênis/ultraestruturaRESUMO
To better understand how the human fetal penis and clitoris grows and remodels, we undertook an investigation to define active areas of cellular proliferation and programmed cell death spatially and temporally during development of human fetal external genitalia from the indifferent stage (8 weeks) to 18 weeks of gestation. Fifty normal human fetal penile and clitoral specimens were examined using macroscopic imaging, scanning electron microscopy and immunohistochemical localization for the cellular proliferation and apoptotic markers, Ki67 and Caspase-3, respectively. A number of hot spots of cellular proliferation characterized by Ki67 localization are present in the penis and clitoris especially early in development, most notably in the corporal body, glans, remodeling glanular urethra, the urethral plate, the roof of the urethral groove and the fully formed penile urethra. The 12-fold increase in penile length over 10 weeks of growth from 8 to 18 weeks of gestation based on Ki67 labelling appears to be driven by cellular proliferation in the corporal body and glans. Throughout all ages in both the developing penis and clitoris Ki67 labeling was consistently elevated in the ventral epidermis and ventral mesenchyme relative to the dorsal counterparts. This finding is consistent with the intense morphogenetic activity/remodeling in the ventral half of the genital tubercle in both sexes involving formation of the urethral/vestibular plates, canalization of the urethral/vestibular plates and fusion of the urethral folds to form the penile urethra. Areas of reduced or absent Ki67 staining include the urethral fold epithelium that fuses to form the penile tubular urethra. In contrast, the urethral fold mesenchyme is positive for Ki67. Apoptosis was rarely noted in the developing penis and clitoris; the only area of minimal Caspase-3 localization was in the epithelium of the ventral epithelial glanular channel remodeling.
Assuntos
Caspase 3/genética , Clitóris/crescimento & desenvolvimento , Antígeno Ki-67/genética , Pênis/crescimento & desenvolvimento , Apoptose/genética , Proliferação de Células/genética , Clitóris/metabolismo , Desenvolvimento Embrionário , Epitélio/crescimento & desenvolvimento , Epitélio/metabolismo , Feminino , Feto , Regulação da Expressão Gênica no Desenvolvimento/genética , Genitália Feminina/crescimento & desenvolvimento , Genitália Feminina/metabolismo , Humanos , Masculino , Microscopia Eletrônica de Varredura , Pênis/metabolismo , Uretra/crescimento & desenvolvimento , Uretra/metabolismoRESUMO
PURPOSE OF REVIEW: Active surveillance is becoming more widely accepted as an initial management option for carefully selected men with favorable intermediate-risk prostate cancer (PCa). As prospective active surveillance cohorts mature sufficiently to begin evaluating longer-term outcomes, consensus on more precise evidence-based guidelines is needed to identify the patient cohorts who may be safely managed with active surveillance and what the ideal surveillance protocol entails. RECENT FINDINGS: Long-term outcomes updates have suggested a trend toward worse 15-year survival outcomes for intermediate-risk patients on active surveillance compared with definitive treatment, but 'intermediate-risk' is a broad category and there is a subset of favorable intermediate-risk patients for whom survival outcomes remain equivalent. Promising updates to current risk stratification include consideration of genomic classifiers, advanced imaging and more nuanced interpretation of biopsy results. SUMMARY: Despite widespread acknowledgement of the pitfalls of overtreatment in clinically localized PCa, utilization of active surveillance in the intermediate-risk population remains marginal, in part due to the absence of easily interpretable consensus recommendations. As more long-term outcomes data become available for this subgroup, the field is now poised to refine the definition of favorable intermediate-risk patients for whom active surveillance is a safe, evidence-based first-line management option.
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Neoplasias da Próstata/diagnóstico , Medição de Risco/métodos , Conduta Expectante , Intervalo Livre de Doença , Humanos , Masculino , Gradação de Tumores , Antígeno Prostático Específico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Fatores de RiscoRESUMO
The human penis and clitoris develop from the ambisexual genital tubercle. To compare and contrast the development of human penis and clitoris, we used macroscopic photography, optical projection tomography, light sheet microscopy, scanning electron microscopy, histology and immunohistochemistry. The human genital tubercle differentiates into a penis under the influence of androgens forming a tubular urethra that develops by canalization of the urethral plate to form a wide diamond-shaped urethral groove (opening zipper) whose edges (urethral folds) fuse in the midline (closing zipper). In contrast, in females, without the influence of androgens, the vestibular plate (homologue of the urethral plate) undergoes canalization to form a wide vestibular groove whose edges (vestibular folds) remain unfused, ultimately forming the labia minora defining the vaginal vestibule. The neurovascular anatomy is similar in both the developing human penis and clitoris and is the key to successful surgical reconstructions.
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Clitóris/crescimento & desenvolvimento , Microscopia Eletrônica de Varredura/métodos , Pênis/crescimento & desenvolvimento , Uretra/crescimento & desenvolvimento , Clitóris/ultraestrutura , Feminino , Humanos , Masculino , Pênis/ultraestrutura , Uretra/ultraestruturaRESUMO
Recent studies in our lab have utilized three imaging techniques to visualize the developing human fetal urogenital tract in three dimensions: optical projection tomography, scanning electron microscopy and lightsheet fluorescence microscopy. We have applied these technologies to examine changes in morphology and differential gene expression in developing human external genital specimens from the ambisexual stage (<9 weeks fetal age) to well-differentiated male and female organs (>13 weeks fetal age). This work outlines the history and function of each of these three imaging modalities, our methods to prepare specimens for each and the novel findings we have produced thus far. We believe the images in this paper of human fetal urogenital organs produced using lightsheet fluorescence microscopy are the first published to date.
Assuntos
Desenvolvimento Fetal/genética , Imageamento Tridimensional/métodos , Diferenciação Sexual/genética , Sistema Urogenital/ultraestrutura , Feminino , Humanos , Masculino , Microscopia Eletrônica de Varredura , Sistema Urogenital/crescimento & desenvolvimentoRESUMO
We recently described a two-step process of urethral plate canalization and urethral fold fusion to form the human penile urethra. Canalization ("opening zipper") opens the solid urethral plate into a groove, and fusion ("closing zipper") closes the urethral groove to form the penile urethra. We hypothesize that failure of canalization and/or fusion during human urethral formation can lead to hypospadias. Herein, we use scanning electron microscopy (SEM) and analysis of transverse serial sections to better characterize development of the human fetal penile urethra as contrasted to the development of the human fetal clitoris. Eighteen 7-13 week human fetal external genitalia specimens were analyzed by SEM, and fifteen additional human fetal specimens were sectioned for histologic analysis. SEM images demonstrate canalization of the urethral/vestibular plate in the developing male and female external genitalia, respectively, followed by proximal to distal fusion of the urethral folds in males only. The fusion process during penile development occurs sequentially in multiple layers and through the interlacing of epidermal "cords". Complex epithelial organization is also noted at the site of active canalization. The demarcation between the epidermis of the shaft and the glans becomes distinct during development, and the epithelial tag at the distal tip of the penile and clitoral glans regresses as development progresses. In summary, SEM analysis of human fetal specimens supports the two-zipper hypothesis of formation of the penile urethra. The opening zipper progresses from proximal to distal along the shaft of the penis and clitoris into the glans in identical fashion in both sexes. The closing zipper mechanism is active only in males and is not a single process but rather a series of layered fusion events, uniquely different from the simple fusion of two epithelial surfaces as occurs in formation of the palate and neural tube.
Assuntos
Epitélio/ultraestrutura , Desenvolvimento Fetal , Pênis/ultraestrutura , Uretra/ultraestrutura , Clitóris/crescimento & desenvolvimento , Clitóris/ultraestrutura , Epitélio/crescimento & desenvolvimento , Feminino , Genitália Feminina/crescimento & desenvolvimento , Genitália Feminina/ultraestrutura , Humanos , Hipospadia/fisiopatologia , Masculino , Microscopia Eletrônica de Varredura , Pênis/crescimento & desenvolvimento , Uretra/crescimento & desenvolvimentoRESUMO
This review details methods for utilizing D & C suction abortus specimens as a source of human fetal organs to study the morphogenetic and molecular mechanisms of human fetal organ development. By this means it is possible to design experiments elucidating the molecular mechanisms of human fetal organ development and to compare and contrast human developmental mechanisms with that of laboratory animals. Finally human fetal organs can be grown in vivo as grafts to athymic mice, thus allowing ethical analysis of potential adverse effects of environmental toxicants.
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Feto Abortado/transplante , Diferenciação Celular/genética , Organogênese/genética , Animais , Ecotoxicologia , Regulação da Expressão Gênica no Desenvolvimento , Humanos , CamundongosRESUMO
PURPOSE: We characterized the early gestation development of the female external genitalia using optical projection tomography to visualize anatomical structures at high resolution. MATERIALS AND METHODS: First and early second trimester human female fetal external genitalia were collected with consent after voluntary termination. Specimens labeled with anti-E-Cadherin antibody underwent analysis with optical projection tomography. Histological sections were immunostained for androgen receptor, 5α-reductase, Ki67 for proliferation and Caspase 3 for apoptosis. RESULTS: Three-dimensional reconstructions demonstrated proximal to distal canalization of the epithelial vestibular plate and formation of a vestibular groove, which remained open. Ki67 was observed throughout with greatest density in the dorsal vestibular plate at the level of the opening groove. Staining for Caspase 3 was minimal in all sections. Androgen receptor staining was seen throughout the mesenchyme and in the apical epithelium of the dorsal vestibular groove. Throughout the epithelium and epidermis 5α-reductase staining was observed. CONCLUSIONS: Early development of the external genitalia in the female is analogous to that in the male, demonstrating a similar opening zipper driving canalization of the vestibular plate with localized epithelial proliferation in the absence of significant apoptosis. Thus we hypothesize that the mechanism underlying the opening zipper must be androgen independent and the absence of androgen driven urethral fusion characterizes the normal development of the human clitoris.
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Clitóris/embriologia , Feminino , Idade Gestacional , Humanos , Imageamento Tridimensional , Tomografia Óptica , Uretra/embriologiaRESUMO
Urethral atresia is a rare but clinically significant cause of congenital lower urinary tract obstruction. Initial management options include urinary diversion until definitive urethral reconstruction or progressive urethral dilation. Given the overall rarity of the condition, there are no evidence-based guidelines for the immediate and long-term management of urethral atresia, and clinical practice varies widely. We present an illustrative case managed with progressive urethral dilation alongside urinary diversion to highlight key factors in shared clinical decision making. Ultimately, pooled multi-institutional long-term outcomes data are needed to better guide practice for these patients and their families.
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Síndrome do Abdome em Ameixa Seca , Doenças Uretrais , Derivação Urinária , Humanos , Uretra/cirurgia , Dilatação , Derivação Urinária/métodosRESUMO
There is a broad range of variant phenotypes that can occur within the bladder exstrophy and epispadias complex spectrum. Accurate prenatal detection helps prepare families and to coordinate subspecialty resources. Here, we present the case of a patient with prenatally diagnosed patient with covered cloacal exstrophy variant along with four additional cases illustrating the nonlinear spectrum from isolated epispadias to cloacal exstrophy. Given the rarity of these variants overall and of each subtype within the spectrum, there is a need for long-term multi-institutional outcomes data to improve detection, characterization, and prognostication for these patients.
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Malformações Anorretais , Extrofia Vesical , Epispadia , Gravidez , Feminino , Humanos , Epispadia/diagnóstico , Epispadia/cirurgia , Extrofia Vesical/diagnóstico , Extrofia Vesical/cirurgiaRESUMO
INTRODUCTION: Robot-assisted Laparoscopic Appendicovesicostomy (RALAPV) is increasingly performed as a minimally invasive alternative to the open appendicovesicostomy (OPAV), but questions remain regarding the efficacy of the RALAPV compared to OPAV. OBJECTIVE: To assess and compare outcomes for non-augmented RALAPV to the open surgical approach. MATERIALS AND METHODS: An IRB approved prospective registry was retrospectively examined to abstract all patients who underwent APV without augment between 2012 and 2023. Baseline demographics, intra and post-operative characteristics, and long-term outcomes were aggregated and compared. P-values were two sided and a p-value <0.05 was considered statistically significant. RESULTS: 52 children were identified, 19 (36.5%) OAPV and 33 (63.5%) RALAPV. The median age at surgery was 8.5 years for OAPV and 9.3 years for RALAPV (p = 0.29). Longer operative time was noted in the RALPAV group (346 min vs 289 min, p = 0.04), with a lower estimated blood loss (5 cc vs 30 cc, p = 0.003), shorter median length of hospital stay (4 days vs 5 days, p = 0.07), and lower IV morphine administration (0.04 mg/kg/d vs 0.09 mg/kg/d, p = 0.01). Similar surgical reintervention rate was seen in both cohorts (42% OAPV vs 36% RALAPV, p = 0.77). At the end of follow-up, continence was achieved in 18 (95%) OAPV and 33 (100%) RALAPV patients (p = 0.37) CONCLUSIONS: RALAPV shows comparable success to patients who underwent OPAV procedures. The longer follow-up interval for OPAV highlights minimally invasive surgery as a recent adoption.
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INTRODUCTION/BACKGROUND: Ureteroceles are often diagnosed antenatally and incidentally and treated in a minimally invasive fashion with endoscopic puncture. Recent literature suggests that observation, or non-operative management, is an effective and viable management option in select patients with ureteroceles and certain radiologic findings, however there is no consensus on how to best select patients for non-operative management. OBJECTIVE: To 1) determine if pediatric ureteroceles managed non-operatively require less or sooner secondary surgical intervention than those managed with up-front incision, 2) describe characteristics of success and failure in pediatric ureteroceles managed non-operatively, and 3) identify risk factors associated with receiving intervention and time to intervention. RESULTS: Of 287 ureteroceles, 65 (23%) were managed non-operatively and underwent secondary surgical intervention less frequently (9% vs. 34%, P < 0.01) and later (median age 40 vs. 20 months) than those managed with puncture. Successful non-operative management was associated with fewer comorbidities, smaller ureterocele size, absence of vesicoureteral reflux (VUR) and high-grade VUR, single collecting system, lesser degree of hydronephrosis, ipsilateral MCDK and intravesical location. For all ureteroceles, high-grade VUR, duplex system, and female sex were associated with shorter time to secondary intervention (intervention after initial management). DISCUSSION: In the largest retrospective review of ureterocele management, smaller ureterocele size, absence of high-grade VUR, single system, ipsilateral MCDK and minimal hydronephrosis were factors that increased the efficacy of non-operative management of select pediatric ureteroceles. Furthermore, time to event analysis showed that non-operative management did not predispose patients to sooner secondary intervention (Figure). Lack of a standardized protocol for ureterocele management is a limitation of this single institution retrospective study as it introduces selection bias to the results, however few patients with low risk characteristics underwent puncture and no high risk patients were observed. CONCLUSION: Smaller ureterocele size, absence of high-grade VUR, single system, ipsilateral MCDK and minimal hydronephrosis are factors that may increase the efficacy of non-operative management of select pediatric ureteroceles, which may delay or avoid secondary surgical intervention.
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We have much to learn from other living organisms when it comes to engineering strategies to combat bacterial infections. This study describes the fabrication of cicada wing-inspired nanotopography on commercially pure (CP) nitrile sheets and nitrile gloves for medical use using the reactive ion etching (RIE) technique. Antibacterial activity against P. aeruginosa was tested using two different surface morphologies. It was observed that the etched nitrile surfaces effectively minimized bacterial colonization by inducing membrane damage. Our findings demonstrate a single-step dry etching method for creating mechanobactericidal topographies on nitrile-based surfaces. These findings have utility in designing next-generation personal protective gear in the clinical setting and for many other important applications in the age of antimicrobial resistance.
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Anti-Infecciosos , Nitrilas , Nitrilas/farmacologia , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Luvas Protetoras , Equipamento de Proteção Individual , Pseudomonas aeruginosaRESUMO
CONTEXT: The current EAU/ESPU and recently retired AAP pediatric UTI guidelines recommend renal bladder ultrasound after first febrile UTI in children to screen for structural abnormalities, regardless of findings on prenatal ultrasound. OBJECTIVE: Test the hypothesis that a normal prenatal ultrasound could rule out urinary tract abnormality on post-UTI ultrasound. DATA SOURCES: Medline, Embase, Cochrane Library. STUDY SELECTION: Studies including pediatric patients with first febrile UTI who had both prenatal and post-UTI ultrasound. DATA EXTRACTION: Anatomical abnormalities detected by prenatal and post-UTI ultrasound as reported per individual study criteria were extracted. Meta-analyses of 9 studies (2981 patients) were performed using a random-effects model and composite estimates of the negative predictive value (NPV) of prenatal ultrasound were calculated. RESULTS: Overall summary NPV of prenatal ultrasound for all pediatric patients was 77%, with heterogeneity score (I2) 97.9%. Summary NPV of prenatal ultrasound for all patients under two years of age was similar at 75%, with I2 98.2% For the 4 studies to which we could apply a more stringent definition of abnormality, summary NPV was 85% and I2 97.5% for prediction of moderate post-UTI ultrasound abnormalities and summary NPV was 93% and I2 90.4% for severe abnormalities. DISCUSSION: While we calculated an 85% NPV for a normal prenatal ultrasound to rule out significant postnatal abnormality as defined within individual studies, substantial heterogeneity amongst publications limited the precision of our estimates. This highlights the need for more rigorous investigations with attention to timing of ultrasound and the application of clinically meaningful definitions for abnormal prenatal and post-UTI studies. This may allow judicious use of prenatal ultrasound to guide clinical management for children with first febrile UTI and minimize redundant imaging with potential for false positive results. Until then, the current guidelines are justified based on the limited and heterogenous data from the currently available published studies.
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Infecções Urinárias , Sistema Urinário , Anormalidades Urogenitais , Humanos , Criança , Gravidez , Lactente , Feminino , Valor Preditivo dos Testes , Infecções Urinárias/complicações , Infecções Urinárias/diagnóstico por imagem , Sistema Urinário/diagnóstico por imagem , Rim/diagnóstico por imagem , Febre/etiologia , Ultrassonografia Pré-NatalRESUMO
OBJECTIVE: To rank percentages of underrepresented residents in surgical subspecialties and understand the experience of mentees and mentors who participated in the inaugural University of California, San Francisco Urology UnderRepresented Trainees Entering Residency (UReTER) Mentorship Program for Black, Indigenous, and/or LatinX medical students applying into urology. METHODS: Medical student mentees across the country were recruited via social media and email listservs. Demographic information and photos of mentors were presented on the UReTER website. Medical students could choose a mentor, and once matched, both parties were notified. A survey was emailed to all participants on Urology Match Day 2021. RESULT: The 2018 -2019 ACGME Databook showed underrepresented minority residents made up 7.6% of urology residents, lagging behind neurosurgery, vascular surgery, general surgery, and obstetrics and gynecology. 71 mentees and 101 mentors volunteered for the UReTER Mentorship Program (71 mentor-mentee couplets). Overall response rate was 51% [33 mentors and 32 mentees]. Of mentees who completed the survey, 16 (47%) participated in the 2021 Urology Match; 15 (94%) matched and 6 (38%) felt that UReTER helped them match. CONCLUSION: Feedback on this pilot program was very positive including a high match rate among those who participated. Future changes to the program include expanded student outreach, increased structure, broadened mentor network. The implementation of a low-cost program to increase underrepresented applicants into Urology has great potential to increase representation and improve the field. This program can and should be replicated in all subspecialties.