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Rationale: Non-cystic fibrosis bronchiectasis (NCFB) may originate in bronchiolar regions of the lung. Accordingly, there is a need to characterize the morphology and molecular characteristics of NCFB bronchioles. Objectives: Test the hypothesis that NCFB exhibits a major component of bronchiolar disease manifest by mucus plugging and ectasia. Methods: Morphologic criteria and region-specific epithelial gene expression, measured histologically and by RNA in situ hybridization and immunohistochemistry, identified proximal and distal bronchioles in excised NCFB lungs. RNA in situ hybridization and immunohistochemistry assessed bronchiolar mucus accumulation and mucin gene expression. CRISPR-Cas9-mediated IL-1R1 knockout in human bronchial epithelial cultures tested IL-1α and IL-1ß contributions to mucin production. Spatial transcriptional profiling characterized NCFB distal bronchiolar gene expression. Measurements and Main Results: Bronchiolar perimeters and lumen areas per section area were increased in proximal, but not distal, bronchioles in NCFB versus control lungs, suggesting proximal bronchiolectasis. In NCFB, mucus plugging was observed in ectatic proximal bronchioles and associated nonectatic distal bronchioles in sections with disease. MUC5AC and MUC5B mucins were upregulated in NCFB proximal bronchioles, whereas MUC5B was selectively upregulated in distal bronchioles. Bronchiolar mucus plugs were populated by IL-1ß-expressing macrophages. NCFB sterile sputum supernatants induced human bronchial epithelial MUC5B and MUC5AC expression that was >80% blocked by IL-1R1 ablation. Spatial transcriptional profiling identified upregulation of genes associated with secretory cells, hypoxia, interleukin pathways, and IL-1ß-producing macrophages in mucus plugs and downregulation of epithelial ciliogenesis genes. Conclusions: NCFB exhibits distinctive proximal and distal bronchiolar disease. Both bronchiolar regions exhibit bronchiolar secretory cell features and mucus plugging but differ in mucin gene regulation and ectasia.
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Bronquiectasia , Fibrose Cística , Humanos , Bronquíolos , Dilatação Patológica , Bronquiectasia/genética , Mucinas/metabolismo , Interleucina-1beta , Fibrose , RNA , Mucina-5AC/genéticaRESUMO
PURPOSE: Pregnancies complicated by prenatally suspected lower urinary tract obstruction (LUTO) can be associated with high rates of terminations due to potentially poor outcomes. Herein, we assessed autopsy findings of fetuses terminated for suspected LUTO to evaluate the prenatal diagnostic accuracy and spectrum of underlying pathologies. MATERIALS AND METHODS: We performed a retrospective review of all pregnancies referred to a high-risk fetal center in a universal access to care health care system for suspected LUTO that opted for termination of pregnancy between 2009 and 2022. Ultrasound features, genetic investigations, placental findings, and distribution of postmortem diagnoses were assessed. RESULTS: Of a total of 190 pregnancies with suspected LUTO evaluated during the study period, 79 (42%) were terminated. We excluded 35 fetuses with incomplete data, resulting in 44 available for analysis. Pregnancies were terminated at a mean gestation of 22 ± 5 weeks. A LUTO diagnosis was confirmed in 37 (84.1%) fetuses (35 males, 2 females), and the remaining 7 showed other pathologies. Pulmonary hypoplasia was found in 62.2% (n = 23) and placental pathologies in 56.8% of confirmed LUTO compared to 33.4% and 71.4% in non-LUTO cases, respectively. Overall, a total of 31 fetuses underwent additional prenatal investigations with genetic anomalies detected only in fetuses with a confirmed LUTO diagnosis (13.6%). CONCLUSIONS: In our health care system, almost half of prenatally suspected LUTO pregnancies are terminated. The sonographic diagnostic accuracy for LUTO is reasonable at 84%. However, the remaining 16% still had significant pathologies. Genetic abnormalities are uncommon and rarely the trigger for pregnancy terminations.
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Doenças Fetais , Doenças Uretrais , Obstrução Uretral , Sistema Urinário , Masculino , Gravidez , Humanos , Feminino , Doenças Fetais/diagnóstico por imagem , Doenças Fetais/genética , Placenta , Feto , Estudos Retrospectivos , Ultrassonografia Pré-Natal/métodosRESUMO
PURPOSE: We describe long-term outcomes, including UTIs and need for reimplantation, after ureterovesicostomy (UV) as a lasting surgical procedure for children with primary obstructive megaureter (POM). MATERIALS AND METHODS: Children referred to our institution between 2016 and 2023 who underwent refluxing UV were analyzed. POM was defined as hydroureteronephrosis with distal ureteral dilatation > 7 mm and a negative workup for other etiologies of hydronephrosis. We assessed for surgical outcomes, complications, rate of UTI, and improvement in upper tract dilatation. Statistical analyses assessed for change in hydronephrosis metrics over follow-up. RESULTS: Among 183 patients diagnosed with POM, 47 (24%) underwent UV. Median age of presentation, surgery, and follow-up was 2, 9, and 43 months, respectively. A total of 7 patients developed 30-day complications: Clavien-Dindo grade 1 in 2 (transient urinary retention) and grade 2 in 5 (UTIs). During monitoring 14 (30%) developed UTIs and 7 (15%) required ureteral reimplant or UV takedown. After surgery there was a significant decrease in the proportion of patients with high-grade hydronephrosis, anteroposterior renal pelvis diameter, and maximum ureteral dilatation. CONCLUSIONS: Refluxing UV is a safe alternative to cutaneous diversion in POM. Most patients had improvement in upper tract dilatation with an acceptable short-term complication rate and need for reoperation (in comparison to routine later reimplantation). Our experience suggests that monitoring alone after UV is feasible, and that selective subsequent reconstruction is a reasonable strategy.
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Ureter , Obstrução Ureteral , Humanos , Masculino , Feminino , Obstrução Ureteral/cirurgia , Obstrução Ureteral/etiologia , Pré-Escolar , Lactente , Seguimentos , Estudos Retrospectivos , Ureter/cirurgia , Ureter/anormalidades , Ureter/diagnóstico por imagem , Resultado do Tratamento , Derivação Urinária/métodos , Derivação Urinária/efeitos adversos , Refluxo Vesicoureteral/cirurgia , Refluxo Vesicoureteral/etiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Hidronefrose/etiologia , Hidronefrose/cirurgia , Reimplante/métodos , Reimplante/efeitos adversos , Cistostomia/métodosRESUMO
OBJECTIVE: We sought to determine the effect of secondary management strategies in addition to urotherapy on bowel bladder dysfunction outcomes. STUDY DESIGN: The review protocol was prospectively registered (CRD42023422168). MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL, and Scopus (database initiation until June 2023) were searched. Comparative studies of secondary management strategies vs conventional urotherapy alone were included. Two authors independently screened titles, abstracts, and reviewed full-text articles. Two authors extracted data related to study characteristics, methodology, subjects, and results. RESULTS: In this systematic review and meta-analysis of 18 studies and 1228 children, secondary management strategies (home-based education, biofeedback, and physical therapy) were associated with reduced symptom burden, fewer recurrent urinary tract infections, and improved uroflowmetry findings than children treated solely with urotherapy for conservative management. CONCLUSIONS: Although there is significant reporting heterogeneity, secondary conservative management strategies such as home education, biofeedback or cognitive behavioral therapy, and physiotherapy-based education are associated with less urinary incontinence, fewer infections, and fewer abnormal uroflowmetry findings.
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OBJECTIVE: To sensitively predict the risk of renal obstruction on diuretic renography using routine reported ultrasonography (US) findings, coupled with machine learning approaches, and determine safe criteria for deferral of diuretic renography. PATIENTS AND METHODS: Patients from two institutions with isolated hydronephrosis who underwent a diuretic renogram within 3 months following renal US were included. Age, sex, and routinely reported US findings (laterality, kidney length, anteroposterior diameter, Society for Fetal Urology [SFU] grade) were abstracted. The drainage half-times were collected from renography and stratified as low risk (<20 min, primary outcome), intermediate risk (20-60 min), and high risk of obstruction (>60 min). A random Forest model was trained to classify obstruction risk, here named the 'Artificial intelligence Evaluation of Renogram Obstruction' (AERO). Model performance was determined by measuring area under the receiver-operating-characteristic curve (AUROC) and decision curve analysis. RESULTS: A total of 304 patients met the inclusion criteria, with a median (interquartile range) age of diuretic renogram at 4 (2-7) months. Of all patients, 48 (16%) were low risk, 102 (33%) were intermediate risk, 156 (51%) were high risk of obstruction based on diuretic renogram. The AERO achieved a binary AUROC of 0.84, multi-class AUROC of 0.74 that was superior to the SFU grade, and external validation (n = 64) binary AUROC of 0.76. The most important features for prediction included age, anteroposterior diameter, and SFU grade. We deployed our application in an easy-to-use application (https://sickkidsurology.shinyapps.io/AERO/). At a threshold probability of 30%, the AERO would allow 66 more patients per 1000 to safely avoid a renogram without missing significant obstruction compared to a strategy in which a renogram is routinely performed for SFU Grade ≥3. CONCLUSIONS: Coupled with machine learning, routine US findings can improve the criteria to determine in which children with isolated hydronephrosis a diuretic renogram can be safely avoided. Further optimisation and validation are required prior to implementation into clinical practice.
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Hidronefrose , Obstrução Ureteral , Humanos , Criança , Lactente , Inteligência Artificial , Hidronefrose/diagnóstico por imagem , Renografia por Radioisótopo , Ultrassonografia , Diuréticos/uso terapêutico , Aprendizado de Máquina , Obstrução Ureteral/diagnóstico por imagem , Estudos RetrospectivosRESUMO
BACKGROUND: Children with prune belly syndrome (PBS) are at higher risk of developing kidney dysfunction and requiring kidney replacement therapy (KRT). While studies have described surgical and survival outcomes in these populations, there has yet to be a focused synthesis of evidence regarding kidney outcomes in this population. Here, the focus of this scoping review was to highlight knowledge gaps and report standards on kidney outcomes in PBS of all ages. METHODS: Following scoping review methodology, EMBASE, MEDLINE, and Scopus were searched for peer-reviewed literature that describe kidney outcomes in PBS. All studies with a broad set of kidney outcomes (such as kidney function measures, chronic kidney disease (CKD), KRT and associated outcomes) were included. Findings were summarized and qualitatively synthesized. RESULTS: Of the 436 unique records identified, 25 were included for synthesis. A total of 17 studies (441 patients) reported on kidney insufficiency outcomes, with an estimated prevalence of CKD ranging from 8 to 66%. A total of 15 studies (314 patients) described KRT, primary kidney transplant, and outcomes. Of these, the age for KRT ranged from 4 to 21 years, and graft survival ranged from 22 to 87% by last follow-up (range 1.3-27 years). CONCLUSIONS: There is significant variability in studies reporting kidney outcomes in PBS which limits meaningful synthesis. There is a need for future studies with comprehensive reporting of confounders and drivers for kidney insufficiency in PBS.
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Transplante de Rim , Síndrome do Abdome em Ameixa Seca , Insuficiência Renal Crônica , Criança , Humanos , Pré-Escolar , Adolescente , Adulto Jovem , Adulto , Síndrome do Abdome em Ameixa Seca/complicações , Transplante de Rim/efeitos adversos , Rim/cirurgia , Terapia de Substituição Renal/métodos , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/complicaçõesRESUMO
INTRODUCTION: A nomogram for predicting the diagnosis of lower urinary tract obstruction (LUTO) based on an antenatal ultrasound index generated from a Bayesian Meta-regression analysis has been in development and noted with superior diagnostic accuracy compared to the keyhole sign (KHS). We aim to assess the accuracy of the nomogram in expanded diagnostic utilization to predict LUTO. METHODOLOGY: The validation of the nomogram for expanded diagnostic utilization was based on data from a prospective institutional antenatal clinic database between January 2020 and June 2022. Diagnostic accuracy indices were determined for confirmed postnatal diagnosis of LUTO or prune belly syndrome (PBS). Receiver operating characteristics (ROC) curves were generated to compare the area under the curve (AUC) of the nomogram versus KHS. RESULTS: Based on 84 male fetuses with antenatal ultrasound of moderate-severe hydronephrosis (PUV n = 15, PBS n = 4), the KHS had 26.3% (95%CI 9.1-51.2) sensitivity and 100% (95%CI 94.4%-100%) specificity, with 14 false-negatives. The nomogram showed a 84.2 (95%CI 60.4%-96.6%) sensitivity and 95.4 (95%CI 87.1%-99%) specificity with three false-positives. The nomogram also had a superior AUC compared to KHS (0.98 vs. 0.63). CONCLUSION: The nomogram can be used as a valuable tool to trigger further postnatal screening and provide individualized risk assessments to families during prenatal counseling.
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Síndrome do Abdome em Ameixa Seca , Sistema Urinário , Humanos , Masculino , Gravidez , Feminino , Nomogramas , Estudos Prospectivos , Teorema de Bayes , Ultrassonografia Pré-NatalRESUMO
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.
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Hipospadia , Pênis , Uretra , Humanos , Hipospadia/classificação , Masculino , Lactente , Fotografação/métodos , Pré-Escolar , Variações Dependentes do Observador , Reprodutibilidade dos Testes , CriançaRESUMO
Introduction: Congenital penile curvature (PC), often concomitant with hypospadias, poses challenges in urology. Surgical correction techniques, including plication and corporotomy, lack standardized guidelines. This study aims to address the paucity of high-level evidence by comprehensively reviewing the outcomes of PC correction procedures in patients with and without hypospadias. This will inform clinical decision-making and provide insights for future research and meta-analyses. Methods: We conducted this scoping review in accordance with the JBI Manual for Evidence Synthesis and PRISMA-ScR guidelines. An extensive literature search was performed and comparative studies published in English up to June 2023 were included. The studies were divided into three categories: PC without hypospadias, PC with hypospadias, and studies comparing two or more materials for covering the ventral corporotomy. Data extraction comprised author details, patient characteristics, study design, interventions, outcomes, and complications. Methodological quality was assessed using the Newcastle-Ottawa Scale. Results: Forty-two studies were included in the review, which collectively comprised 3180 patients. Thirteen comparative studies reported the outcomes of surgery for congenital PC without hypospadias, 22 studies compared different techniques of PC correction in patients with hypospadias and 7 studies compared the type of materials for coverage following ventral corporotomy. In cases of PC without hypospadias, the most commonly reported surgery was the Nesbit's plication. For PC with hypospadias correction, the results of ventral corporotomy were superior to that of dorsal plication in most of the studies. The two-stage repair had better results when compared to the one-stage repair for patients with perineo-scrotal hypospadias. In studies comparing materials for coverage of ventral corporotomy, the tunica vaginalis flap or graft was utilized most commonly. The majority of the studies reported a success rate ranging from 85% to 100%. The methodological quality was high in all but four studies. Conclusion: Plication procedures are generally preferred for PC without hypospadias, but they result in penile shortening. For those with hypospadias, corporotomy is associated with superior outcomes than plication, especially for those with severe curvature and redo procedures. For ventral corporotomy coverage, the tunica vaginalis flap or graft is the most commonly reported tissue in the literature.
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OBJECTIVE: To compare and assess the clinical outcomes between thulium fibre laser (TFL) and holmium: yttrium-aluminium-garnet (Ho:YAG) laser endoscopic lithotripsy of urolithiasis through a meta-analysis of comparative clinical studies. METHODS: A systematic literature search was performed in May 2022, grey literature search in July 2022. Comparative clinical studies were evaluated according to Cochrane recommendations. Assessed outcomes include the stone-free rate (SFR), complication rate, operative time (OT), laser utilisation time (LUT), ablation rate (stone volume/laser time), ablation efficiency (energy use/stone volume), total energy usage, degree of retropulsion, and hospital stay. Risk ratios (RRs) and standardised mean differences (SMDs) were extrapolated. Subgroup analyses, heterogeneity, publication bias, and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessment were performed. International Prospective Register of Systematic Reviews (PROSPERO) registration: CRD42022300788. RESULTS: A total of 15 studies with 1698 cases were included in this review. The outcome of SFR showed no significant between-group difference (RR 1.09, 95% confidence interval [CI] 0.99-1.20). However, subgroup analysis of TFL vs Ho:YAG with no pulse modulation showed a SFR favouring TFL (RR 1.11, 95% CI 1.01-1.23). The composite postoperative complication rate was comparable between the two intervention groups (RR 0.97, 95% CI 0.66-1.43). OT, LUT and ablation rate were significantly better for TFL than Ho:YAG (SMD -1.19, 95% CI -1.85 to -0.52; SMD -1.67, 95% CI -2.62 to -0.72; SMD 0.59, 95% CI 0.15-1.03; respectively). The degree of retropulsion was significantly lower for TFL than Ho:YAG without pulse modulation (SMD -1.23, 95% CI -1.74 to -0.71). Ablation efficiency, total energy usage, and hospital stay were all comparable. Based on GRADE criteria, the evidence certainty was determined to be very low. CONCLUSION: Overall, there was no between-group difference for the SFR. However, compared to Ho:YAG with no pulse modulation, TFL rendered a better SFR. Shorter OT and LUT, a lesser degree of retropulsion, and a better ablation rate were noted in favour of the TFL. There was no overall between-group difference for composite postoperative complication rate, ablation efficiency, total energy usage, and hospital stay. Currently, the available clinical evidence was assessed to be of very low certainty.
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Cálculos , Lasers de Estado Sólido , Litotripsia a Laser , Urolitíase , Humanos , Litotripsia a Laser/efeitos adversos , Túlio/uso terapêutico , Hólmio/uso terapêutico , Revisões Sistemáticas como Assunto , Lasers de Estado Sólido/uso terapêutico , Complicações Pós-Operatórias/epidemiologiaRESUMO
OBJECTIVE: To examine and critique current international clinical practice guidelines (CPGs) on management of paediatric neurogenic lower urinary tract dysfunction (NLUTD) and assess the applicability of these guidelines to clinical practice. MATERIALS AND METHODS: We conducted a systematic review of all CPGs on NLUTD published in English from the year 2010 to 2022. Six reviewers independently used the Appraisal of Guidelines and Research Evaluation (AGREE) II instrument to appraise all eligible CPGs. This instrument is comprised of 23 items organised into six quality domains. The scores for each item and domain were tabulated for each reviewer and interrater reliability was assessed for each domain using the intraclass correlation coefficient (ICC). RESULTS: Six CPGs were appraised and these included: National Institute for Health and Care Excellence (NICE), European Society for Paediatric Urology, International Children's Continence Society, Irish, Spina Bifida Association (SBA), and International Brazilian Journal of Urology guidelines. They had high mean standardised scores in the domain on 'scope and purpose' and 'clarity of presentation' but had low scores in the domain of 'applicability'. The top three CPGs based on overall score were the NICE, Irish and SBA guidelines and the reviewers had high degree of interrater reliability (ICC 0.912, P < 0.001). The mean scores in various domains for the top three guidelines were 95.8 (scope and purpose), 87.5 (stakeholder involvement), 69.1 (rigour of development), 94.0 (clarity of presentation), 68.4 (applicability), and 59.7 (editorial independence). The diagnostic and treatment recommendations of the top three guidelines were presented. CONCLUSION: The existing CPGs on paediatric NLUTD provide high-quality evidence based recommendations. The NICE, Irish and SBA guidelines were the top three CPGs identified. They scored high on most domains except applicability and editorial independence. These domains need to be considered for future updates to improve the utility.
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Sistema Urinário , Urologia , Humanos , Criança , Reprodutibilidade dos TestesRESUMO
PURPOSE: To determine the role of pressure pop-off mechanisms, including vesicoureteral reflux and renal dysplasia (VURD) syndrome, in determining long-term kidney outcomes in boys with posterior urethral valves (PUV). METHODS: A systematic search was performed in December 2022. Descriptive and comparative studies with a defined pressure pop-off group were included. Assessed outcomes included end-stage renal disease (ESRD), kidney insufficiency (defined as chronic kidney disease [CKD] stage 3 + or SCr > 1.5 mg/dL), and kidney function. Pooled proportions and relative risks (RR) with 95% confidence intervals (CI) were extrapolated from available data for quantitative synthesis. Random-effects meta-analyses were performed according to the study design and techniques. The risk of bias was assessed with the QUIPS tool and GRADE quality of evidence. The systematic review was prospectively registered on PROSPERO (CRD42022372352). RESULTS: A total of 15 studies describing 185 patients with a median follow-up of 6.8 years were included. By the last follow-up, overall effect estimates demonstrate the prevalence of CKD and ESRD to be 15.2% and 4.1%, respectively. There was no significant difference in the risk of ESRD in patients with pop-off compared to no pop-off patients [RR 0.34, 95%CI 0.12, 1.10; p = 0.07]. There was a significantly reduced risk for kidney insufficiency in boys with pop-off [RR 0.57, 95%CI 0.34, 0.97; p = 0.04], but this protective effect was not re-demonstrated after excluding studies with inadequate reporting of CKD outcomes [RR 0.63, 95%CI 0.36, 1.10; p = 0.10]. Included study quality was low, with 6 studies having moderate risk and 9 having a high risk of bias. CONCLUSIONS: Pop-off mechanisms may be associated with reducing the risk of kidney insufficiency, but current certainty in the evidence is low. Further research is warranted to investigate sources of heterogeneity and long-term sequelae in pressure pop-offs.
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Falência Renal Crônica , Insuficiência Renal Crônica , Obstrução Uretral , Masculino , Humanos , Falência Renal Crônica/epidemiologia , Rim , Insuficiência Renal Crônica/complicações , Obstrução Uretral/complicações , Progressão da DoençaRESUMO
BACKGROUND: To determine if the implementation of a posterior urethral valves (PUV) clinic and standardized management pathway improves the short-term kidney outcomes of infants with PUV. METHODS: From 2016-2022, 50 consecutive patients were divided into groups after the implementation of the clinic (APUV, n = 29) and before (BPUV, n = 21) during a comparable timeframe. Assessed data included age at initial visit, timing and type of surgery, frequency of follow-up visits, medications, nadir creatinine, and development of CKD/kidney failure. Data are shown as median with interquartile range (IQR) and odds ratios (OR) with 95% confidence interval (CI). RESULTS: APUV had higher rates of prenatal diagnoses (12/29 vs. 1/21; p = 0.0037), earlier initial surgical intervention (8 days; IQR 0, 105 vs. 33 days; IQR 4, 603; p < 0.0001), and higher rates of primary diversions (10/29 vs. 0/21; p = 0.0028). Standardized management led to earlier initiation of alpha blockers (326 days; IQR 6, 860 vs. 991; IQR 149, 1634; p = 0.0019) and anticholinergics (57 days; IQR 3, 860 vs. 1283 days; IQR 477, 1718; p < 0.0001). Nadir creatinine was reached at earlier ages in APUV (105 days; IQR 2, 303 vs. 164 days; IQR 21, 447; p = 0.0192 BPUV). One patient progressed to CKD5 in APUV compared to CKD3, CKD5 and one transplant in BPUV. CONCLUSION: Implementing the PUV clinic with standardized treatment expedited postnatal management and resulted in a higher number of cases detected prenatally, a shift in primary treatment, younger ages at initial treatment, reduced time to nadir creatinine, and timely initiation of supportive medications. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Uretra , Obstrução Uretral , Lactente , Gravidez , Feminino , Humanos , Uretra/cirurgia , Creatinina , Procedimentos Clínicos , Estudos Retrospectivos , Obstrução Uretral/cirurgiaRESUMO
PURPOSE: ß3-adrenergic receptor agonists (ß3 agonists) have been used in treatment of overactive bladder (OAB) and neurogenic detrusor overactivity (NDO) in adults. However, their use in children has only recently been approved by the U.S. Food and Drug Administration for patients with NDO. As in adults, the role of ß3 agonists in children may include conditions such as OAB. This systematic review and meta-analysis aims to understand the intended use, efficacy and safety of ß3 agonists in the pediatric population. MATERIALS AND METHODS: A literature search was performed in February 2021 across MEDLINE®, Embase®, Scopus®, the Cochrane Library and ClinicalTrials.gov. No language restrictions were placed. All records describing the clinical use of ß3 agonists in pediatric patients (<18 years of age) were included, regardless of the methodological design or outcomes assessed. The identified records were screened by 2 independent authors. The reporting was compliant with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Data extraction was performed by 2 independent reviewers, blinded to each other's extractions. The data were pooled using the fixed effects model. RESULTS: Of 367 records identified, 8 studies were included in the review (3 prospective and 5 retrospective). ß3 agonists led to improvements in both urodynamics parameters and self-reported outcomes such as incontinence. Commonly reported side effects were headaches (3%â5.9%), constipation (3.5%â5.7%), rhinitis/nasopharyngitis (1.7%â5.8%) and blurred vision (1.7%â2.9%). Clinically meaningful changes in safety outcomes (blood pressure, heart rate, electrocardiogram-related changes, liver function) were rare. Before and after ß3 agonist use, pooled effect estimates for maximum cystometric capacity for 171 patients were mean difference of +98.84 ml (95% CI 74.72, 122.96); for complete dryness, assessment of 235 patients showed a Peto odds ratio of 8.68 (95% CI 5.22, 14.45). CONCLUSIONS: ß3 agonists appear to be a promising, effective and safe alternative/adjunctive therapy in management of pediatric NDO or OAB, with improvements in both objective urodynamics parameters and subjective patient-reported outcomes following their use.
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Agonistas de Receptores Adrenérgicos beta 3/uso terapêutico , Bexiga Urinaria Neurogênica/tratamento farmacológico , Bexiga Urinária Hiperativa/tratamento farmacológico , Agonistas de Receptores Adrenérgicos beta 3/efeitos adversos , Criança , Humanos , Incontinência Urinária/induzido quimicamente , Urodinâmica/efeitos dos fármacosRESUMO
OBJECTIVE: To identify and critically appraise available clinical practice guidelines (CPGs) targeting male circumcision using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument. STUDY DESIGN: A literature search was conducted using electronic databases, CPG databases, and national/international societies providing recommendations to guide clinical decision making for male circumcision. We selected pediatric-focused CPGs related to male circumcision published between January 2010 and December 2020. Non-English CPGs and publications involving narrative reviews, primary research, training manuals, patient and allied health professional guidelines, and technical guides were excluded from our search. Complete CPG documents (including full-text articles, supplemental documents, and associated information) were reviewed. Quality appraisal of CPGs was conducted in accordance with the AGREE II manual. RESULTS: A total of 163 CPGs were identified, of which 93 were screened and 13 were reviewed. All AGREE II domains demonstrated good to excellent interrater reliability, with intraclass correlation coefficients ranging from 0.82 (95% CI, 0.72-0.89) to 0.93 (95% CI, 0.90-0.95). Most CPGs performed satisfactorily in the clarity of presentation domain and performed poorly in the applicability and editorial independence domains. The top 3 CPGs identified were those of the American Academy of Pediatrics, Centers for Disease Control and Prevention, and Canadian Urological Association. Consistencies among the CPGs were demonstrated across most recommendations. CONCLUSIONS: Current CPGs are of variable quality, and our findings should be taken into consideration by clinicians and health care professionals when selecting appropriate guidelines for male circumcision.
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Circuncisão Masculina , Canadá , Criança , Bases de Dados Factuais , Humanos , Masculino , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To compare the outcomes for laparoscopic vascular hitch (VH) and dismembered pyeloplasty in patients with pelvi-ureteric junction obstruction (PUJO) secondary to crossing vessels (CV). PATIENTS AND METHODS: Patients who underwent laparoscopic management of CV at our institution were identified between 2008 and 2020. Baseline characteristics and outcome measures were compared between those who underwent VH and those who underwent dismembered pyeloplasty. Those who underwent VH were selected intraoperatively by identifying CV in the absence of intrinsic obstruction by assessing resolution of hydronephrosis after cranially displacing the CV away from the PUJ, followed by intraoperative fluid bolus and diuretic test. In addition, a systematic search and meta-analysis were performed in June 2020 (International Prospective Register of Systematic Reviews [PROSPERO] ID CRD42020195833). RESULTS: A total of 20 patients underwent VH and 74 dismembered pyeloplasty. On multivariate analysis, VH was associated with: shorter operative time (P = 0.001; odds ratio [OR] 0.455, 95% confidence interval [CI] 0.294-0.705) and length of stay (P = 0.012; OR 0.383, 95% CI 0.183-0.803), lower use of stents (P < 0.001; OR 0.024, 95% CI 0.004-0.141) and opioid administration (P = 0.005; OR 0.157, 95% CI 0.044-0.567). From our literature search, 194 records were identified and 18 records were included (three comparative and 16 non-comparative). Meta-analysis of the comparative studies and our institutional data showed similar success rates (relative risk [RR] 1.77, 95% CI 0.33-9.52) and complication rates (RR 0.75, 95% CI 0.20-2.82). VH was associated with shorter operative time (standardised mean difference [SMD] -1.65, 95% CI -2.58 to -0.72 h) and hospital stay (SMD -1.41, 95% CI -2.36 to -0.47 days). The VH success rates ranged from 87.5% to 100% in the identified studies. Failure of VH was associated with unrecognised concomitant intrinsic obstruction in addition to CV. CONCLUSIONS: A VH, for well-selected patients with CV without concomitant intrinsic obstruction, offers a high success rate with shorter operative times.
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Laparoscopia , Rim Displásico Multicístico , Obstrução Ureteral , Criança , Humanos , Hidronefrose/congênito , Pelve Renal/cirurgia , Laparoscopia/efeitos adversos , Resultado do Tratamento , Obstrução Ureteral/etiologia , Obstrução Ureteral/cirurgia , Procedimentos Cirúrgicos Urológicos/efeitos adversosRESUMO
OBJECTIVE: To compare the outcomes of pre- vs postnatally diagnosed posterior urethral valves (PUV) at two large paediatric centres in North America to ascertain if the prenatal diagnosis of PUV is associated with better outcomes. PATIENTS AND METHODS: All boys with PUV were identified at two large paediatric institutions in North America between 2000 and 2020 (The Hospital for Sick Children [SickKids, SK] and Children's Hospital of Philadelphia [CHOP]). Baseline characteristics and outcome measures were compared between those diagnosed pre- vs postnatally. Main outcomes of interest included progression of chronic kidney disease (CKD), the need for renal replacement therapy (RRT), and bladder function compromise, as determined by need for clean intermittent catheterisation (CIC). Time-to-event analyses were completed when possible. RESULTS: During the study period, 152 boys with PUV were treated at the SK (39% prenatal) and 216 were treated at the CHOP (71% prenatal). At the SK, there was no difference between the pre- and postnatal groups in the proportion of boys who required RRT, progressed to CKD Stage ≥3, or who were managed with CIC when comparing the timing of diagnosis. The time to event for RRT and CIC was significantly younger for prenatally detected PUV. At the CHOP, significantly more prenatal boys required RRT; however, there was no significant difference in the age this outcome was reached. The proportion of boys managed with CIC was not different but the time to event was significantly earlier in the prenatal group. CONCLUSION: This study represents the largest multi-institutional series of boys with PUV and failed to identify any difference in the outcomes of pre- vs postnatal detection of PUV. A multidisciplinary approach with standardisation of the treatment pathways will help in understanding the true impact of prenatal/early detection on outcomes of PUV.
Assuntos
Insuficiência Renal Crônica , Obstrução Uretral , Criança , Feminino , Humanos , Masculino , Gravidez , Diagnóstico Pré-Natal , Insuficiência Renal Crônica/terapia , Estudos Retrospectivos , UretraRESUMO
OBJECTIVE: To determine through a comprehensive systematic review and meta-analysis the differences in the outcomes of prenatally versus postnatally diagnosed posterior urethral valves (PUV) to ascertain if prenatal detection of PUV has superior outcomes. METHODS: We conducted a systematic review and meta-analysis in March 2022 (PROSPERO ID - CRD42021243546) and included all studies that reported outcomes of prenatally and postnatally diagnosed PUV. However, for meta-analysis, only those studies that described both groups were included. The main outcomes of interest included progression of chronic kidney disease (CKD), need for renal replacement therapy (RRT) and renal transplant, and bladder dysfunction as determined by initiation of clean intermittent catheterization (CIC). Time to event analyses were completed when possible. RESULTS: The systematic review included 49 studies (3820 patients). The pooled effect estimates for progression to CKD (OR 0.75 [95% CI 0.43, 1.31]), need for RRT (OR 1.39 [95% CI 0.64, 2.99]) and need for renal transplant (OR 1.64 [95% CI 0.61, 4.42]) between prenatal and postnatal groups was not different. CICs rates were as high as 32% in the prenatal group and 22% in the postnatal group. Most studies had a moderate or serious risk of bias. CONCLUSION: The existing comparative literature on prenatal versus postnatal presentation of PUV is very heterogeneous. The diagnostic and treatment protocols have not been reported in majority of the studies. The outcome variables are also reported inconsistently. Based on the current evidence, prenatal diagnosis of PUV does not appear to improve the long-term outcomes of these patients.
Assuntos
Transplante de Rim , Insuficiência Renal Crônica , Obstrução Uretral , Feminino , Humanos , Gravidez , Insuficiência Renal Crônica/terapia , Estudos Retrospectivos , Uretra , VitaminasRESUMO
PURPOSE: To develop a model that predicts whether a child will develop a recurrent obstruction after pyeloplasty, determine their survival risk score, and expected time to re-intervention using machine learning (ML). METHODS: We reviewed patients undergoing pyeloplasty from 2008 to 2020 at our institution, including all children and adolescents younger than 18 years. We developed a two-stage machine learning model from 34 clinical fields, which included patient characteristics, ultrasound findings, and anatomical variation. We fit and trained with a logistic lasso model for binary cure model and subsequent survival model. Feature importance on the model was determined with post-selection inference. Performance metrics included area under the receiver-operating-characteristic (AUROC), concordance, and leave-one-out cross validation. RESULTS: A total of 543 patients were identified, with a median preoperative and postoperative anteroposterior diameter of 23 and 10 mm, respectively. 39 of 232 patients included in the survival model required re-intervention. The cure and survival models performed well with a leave-one-out cross validation AUROC and concordance of 0.86 and 0.78, respectively. Post-selective inference showed that larger anteroposterior diameter at the second post-op follow-up, and anatomical variation in the form of concurrent anomalies were significant model features predicting negative outcomes. The model can be used at https://sickkidsurology.shinyapps.io/PyeloplastyReOpRisk/ . CONCLUSION: Our ML-based model performed well in predicting the risk of and time to re-intervention after pyeloplasty. The implementation of this ML-based approach is novel in pediatric urology and will likely help achieve personalized risk stratification for patients undergoing pyeloplasty. Further real-world validation is warranted.
Assuntos
Pelve Renal , Aprendizado de Máquina , Ureter , Obstrução Ureteral , Procedimentos Cirúrgicos Urológicos , Adolescente , Criança , Humanos , Pelve Renal/cirurgia , Laparoscopia , Modelos Biológicos , Recidiva , Estudos Retrospectivos , Medição de Risco , Ureter/cirurgia , Obstrução Ureteral/etiologia , Obstrução Ureteral/cirurgia , Procedimentos Cirúrgicos Urológicos/efeitos adversosRESUMO
INTRODUCTION: To evaluate urethral strictures and to determine appropriate surgical reconstructive options, retrograde urethrograms (RUG) are used. Herein, we develop a convolutional neural network (CNN)-based machine learning algorithm to characterize RUG images between those with urethral strictures and those without urethral strictures. METHODS: Following approval from institutional REB from participating institutions (The Hospital for Sick Children [Toronto, Canada], St. Luke's Medical Centre [Quezon City, Philippines], East Virginia Medical School [Norfolk, United States of America]), retrograde urethrogram images were collected and anonymized. Additional RUG images were downloaded online using web scraping method through Selenium and Python 3.8.2. A CNN with three convolutional layers and three pooling layers were built (Fig. 1). Data augmentation was applied with zoom, contrast, horizontal flip, and translation. The data were split into 90% training and 10% testing set. The model was trained with one hundred epochs. RESULTS: A total of 242 RUG images were identified. 196 were identified as strictures and 46 as normal. Following training, our model achieved accuracy of up to 92.2% with its training data set in characterizing RUG images to stricture and normal images. The validation accuracy using our testing set images showed that it was able to characterize 88.5% of the images correctly. CONCLUSION: It is feasible to use a machine learning algorithm to accurately differentiate between a stricture and normal RUG. Further development of the model with additional RUGs may allow characterization of stricture location and length to suggest optimal operative approach for repair.