Pathological Findings in Fetuses Terminated for Suspected Lower Urinary Tract Obstruction: Experience From a High-Risk Fetal Center in Canada.

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.

The Role of Secondary Conservative Management Strategies in Bladder and Bowel Dysfunction: A Systematic Review and Meta-analysis.

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.

Optimizing Screening for Intrastriatal Interventions in Huntington's Disease Using Predictive Models.

BACKGROUND: Intrastriatal delivery of potential therapeutics in Huntington's disease (HD) requires sufficient caudate and putamen volumes. Currently, volumetric magnetic resonance imaging is rarely done in clinical practice, and these data are not available in large research cohorts such as Enroll-HD. OBJECTIVE: The objective of this study was to investigate whether predictive models can accurately classify HD patients who exceed caudate and putamen volume thresholds required for intrastriatal therapeutic interventions. METHODS: We obtained and merged data for 1374 individuals across three HD cohorts: IMAGE-HD, PREDICT-HD, and TRACK-HD/TRACK-ON. We imputed missing data for clinical variables with >72% non-missing values and used the model-building algorithm BORUTA to identify the 10 most important variables. A random forest algorithm was applied to build a predictive model for putamen volume >2500 mm3 and caudate volume >2000 mm3 bilaterally. Using the same 10 predictors, we constructed a logistic regression model with predictors significant at P < 0.05. RESULTS: The random forest model with 1000 trees and minimal terminal node size of 5 resulted in 83% area under the curve (AUC). The logistic regression model retaining age, CAG repeat size, and symbol digit modalities test-correct had 85.1% AUC. A probability cutoff of 0.8 resulted in 5.4% false positive and 66.7% false negative rates. CONCLUSIONS: Using easily obtainable clinical data and machine learning-identified initial predictor variables, random forest, and logistic regression models can successfully identify people with sufficient striatal volumes for inclusion cutoffs. Adopting these models in prescreening could accelerate clinical trial enrollment in HD and other neurodegenerative disorders when volume cutoffs are necessary enrollment criteria. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Predicting obstruction risk using common ultrasonography parameters in paediatric hydronephrosis with machine learning.

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.

Kidney function and transplants in prune belly syndrome: a scoping review.

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.

Expert classification of hypospadias: an external validation and evaluation of agreement for Glans-Urethral Meatus-Shaft (GMS) and Hypospadias Objective Penile Evaluation (HOPE) scores.

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.

Deep Learning-Based Model for Identifying Tumors in Endoscopic Images From Patients With Locally Advanced Rectal Cancer Treated With Total Neoadjuvant Therapy.

BACKGROUND: A barrier to the widespread adoption of watch-and-wait management for locally advanced rectal cancer is the inaccuracy and variability of identifying tumor response endoscopically in patients who have completed total neoadjuvant therapy (chemoradiotherapy and systemic chemotherapy). OBJECTIVE: This study aimed to develop a novel method of identifying the presence or absence of a tumor in endoscopic images using deep convolutional neural network-based automatic classification and to assess the accuracy of the method. DESIGN: In this prospective pilot study, endoscopic images obtained before, during, and after total neoadjuvant therapy were grouped on the basis of tumor presence. A convolutional neural network was modified for probabilistic classification of tumor versus no tumor and trained with an endoscopic image set. After training, a testing endoscopic imaging set was applied to the network. SETTINGS: The study was conducted at a comprehensive cancer center. PATIENTS: Images were analyzed from 109 patients who were diagnosed with locally advanced rectal cancer between December 2012 and July 2017 and who underwent total neoadjuvant therapy. MAIN OUTCOME MEASURES: The main outcomes were accuracy of identifying tumor presence or absence in endoscopic images measured as area under the receiver operating characteristic for the training and testing image sets. RESULTS: A total of 1392 images were included; 1099 images (468 of no tumor and 631 of tumor) were for training and 293 images (151 of no tumor and 142 of tumor) for testing. The area under the receiver operating characteristic for training and testing was 0.83. LIMITATIONS: The study had a limited number of images in each set and was conducted at a single institution. CONCLUSIONS: The convolutional neural network method is moderately accurate in distinguishing tumor from no tumor. Further research should focus on validating the convolutional neural network on a large image set. See Video Abstract at http://links.lww.com/DCR/B959 . MODELO BASADO EN APRENDIZAJE PROFUNDO PARA IDENTIFICAR TUMORES EN IMGENES ENDOSCPICAS DE PACIENTES CON CNCER DE RECTO LOCALMENTE AVANZADO TRATADOS CON TERAPIA NEOADYUVANTE TOTAL: ANTECEDENTES:Una barrera para la aceptación generalizada del tratamiento de Observar y Esperar para el cáncer de recto localmente avanzado, es la imprecisión y la variabilidad en la identificación de la respuesta tumoral endoscópica, en pacientes que completaron la terapia neoadyuvante total (quimiorradioterapia y quimioterapia sistémica).OBJETIVO:Desarrollar un método novedoso para identificar la presencia o ausencia de un tumor en imágenes endoscópicas utilizando una clasificación automática basada en redes neuronales convolucionales profundas y evaluar la precisión del método.DISEÑO:Las imágenes endoscópicas obtenidas antes, durante y después de la terapia neoadyuvante total se agruparon en base de la presencia del tumor. Se modificó una red neuronal convolucional para la clasificación probabilística de tumor versus no tumor y se entrenó con un conjunto de imágenes endoscópicas. Después del entrenamiento, se aplicó a la red un conjunto de imágenes endoscópicas de prueba.ENTORNO CLINICO:El estudio se realizó en un centro oncológico integral.PACIENTES:Analizamos imágenes de 109 pacientes que fueron diagnosticados de cáncer de recto localmente avanzado entre diciembre de 2012 y julio de 2017 y que se sometieron a terapia neoadyuvante total.PRINCIPALES MEDIDAS DE VALORACION:La precisión en la identificación de la presencia o ausencia de tumores en imágenes endoscópicas medidas como el área bajo la curva de funcionamiento del receptor para los conjuntos de imágenes de entrenamiento y prueba.RESULTADOS:Se incluyeron mil trescientas noventa y dos imágenes: 1099 (468 sin tumor y 631 con tumor) para entrenamiento y 293 (151 sin tumor y 142 con tumor) para prueba. El área bajo la curva operativa del receptor para entrenamiento y prueba fue de 0,83.LIMITACIONES:El estudio tuvo un número limitado de imágenes en cada conjunto y se realizó en una sola institución.CONCLUSIÓN:El método de la red neuronal convolucional es moderadamente preciso para distinguir el tumor de ningún tumor. La investigación adicional debería centrarse en validar la red neuronal convolucional en un conjunto de imágenes mayor. Consulte Video Resumen en http://links.lww.com/DCR/B959 . (Traducción -Dr. Fidel Ruiz Healy ).

Characteristics of Mismatch Repair-Deficient Colon Cancer in Relation to Mismatch Repair Protein Loss, Hypermethylation Silencing, and Constitutional and Biallelic Somatic Mismatch Repair Gene Pathogenic Variants.

BACKGROUND: Mismatch repair-deficient colon cancer is heterogeneous. Differentiating inherited constitutional variants from somatic genetic alterations and gene silencing is important for surveillance and genetic counseling. OBJECTIVE: This study aimed to determine the extent to which the underlying mechanism of loss of mismatch repair influences molecular and clinicopathologic features of microsatellite instability-high colon cancer. DESIGN: This is a retrospective analysis. SETTINGS: This study was conducted at a comprehensive cancer center. PATIENTS: Patients with microsatellite instability-high colon cancer of stage I, II, or III were included. INTERVENTION: Patients underwent a curative surgical resection. MAIN OUTCOME MEASURES: The main outcome measures were hypermethylation of the MLH1 promoter, biallelic inactivation, constitutional pathogenic variants, and loss of specific mismatch repair proteins. RESULTS: Of the 157 identified tumors with complete genetic analysis, 66% had hypermethylation of the MLH1 promoter, 18% had constitutional pathogenic variants, (Lynch syndrome), 11% had biallelic somatic mismatch repair gene pathogenic variants, and 6% had unexplained high microsatellite instability. The distribution of mismatch repair loss was as follows: MLH1 and PMS2 co-loss, 79% of the tumors; MSH2 and MSH6 co-loss, 10%; MSH6 alone, 3%; PMS2 alone, 2%; other combinations, 2%; no loss, 2%. Tumor mutational burden was lowest in MLH1- and PMS2-deficient tumors. MSH6-deficient tumors had the lowest levels of tumor-infiltrating lymphocytes, lowest MSI scores, and fewest frameshift deletions. Patients with MLH1 promoter hypermethylation were significantly more likely to be older and female and to have right-sided colon lesions than patients with biallelic inactivation. Mutation was the most prevalent second hit in tumors with biallelic inactivation and tumors of patients with Lynch syndrome. LIMITATIONS: This study was limited by potential selection or referral bias, missing data for some patients, and relatively small sizes of some subgroups. CONCLUSIONS: Clinical characteristics of mismatch repair-deficient colon cancer vary with the etiology of microsatellite instability, and its molecular characteristics vary with the affected mismatch repair protein. See Video Abstract at http://links.lww.com/DCR/B984 . CARACTERSTICAS DEL CNCER DE COLON CON DEFICIENCIA EN LA REPARACIN DE ERRORES DE EMPAREJAMIENTO EN RELACIN CON LA PRDIDA DE PROTENAS MMR, SILENCIAMIENTO DE LA HIPERMETILACIN Y LAS VARIANTES PATGENAS SOMTICAS DE GENES MMR CONSTITUCIONAL Y BIALLICO: ANTECEDENTES:El cáncer de colon deficiente en la reparación de errores de emparejamiento es heterogéneo. La diferenciación de las variantes constitucionales heredadas de las alteraciones genéticas somáticas y el silenciamiento de genes es importante para la vigilancia y el asesoramiento genético.OBJETIVO:Determinar hasta qué punto el mecanismo subyacente de pérdida de reparación de desajustes influye en las características moleculares y clinicopatológicas del cáncer de colon con alta inestabilidad de microsatélites.DISEÑO:Análisis retrospectivo.ESCENARIO:Centro integral de cáncer.PACIENTES:Pacientes con cáncer de colon con inestabilidad de microsatélites alta en estadio I, II, o III.INTERVENCIÓN:Resección quirúrgica con intención curativa.PRINCIPALES RESULTADOS Y MEDIDAS:Hipermetilación del promotor MLH1, inactivación bialélica, variante patógena constitucional y pérdida de proteínas específicas reparadoras de desajustes.RESULTADOS:De los 157 tumores identificados con un análisis genético completo, el 66 % tenía hipermetilación del promotor MLH1, el 18 % tenía una variante patogénica constitucional (síndrome de Lynch), el 11 % tenía variantes patogénicas somáticas bialélicas de algún gen MMR y el 6 % tenía una alta inestabilidad de microsatélites sin explicación. La distribución de la pérdida según la proteína de reparación del desajuste fue la siguiente: pérdida conjunta de MLH1 y PMS2, 79 % de los tumores; co-pérdida de MSH2 y MSH6, 10%; MSH6 solo, 3%; PMS2 solo, 2%; otras combinaciones, 2%; sin pérdida, 2%. La carga mutacional del tumor fue más baja en los tumores deficientes en MLH1 y PMS2. Los tumores con deficiencia de MSH6 tenían los niveles más bajos de linfocitos infiltrantes de tumores, las puntuaciones más bajas del sensor de IMS y la menor cantidad de deleciones por cambio de marco. Los pacientes con hipermetilación del promotor MLH1 tenían significativamente más probabilidades de ser mayores y mujeres y de tener lesiones en el colon derecho que los pacientes con inactivación bialélica. La mutación fue el segundo golpe más frecuente en tumores con inactivación bialélica y tumores de pacientes con síndrome de Lynch.LIMITACIONES:Sesgo potencial de selección o referencia, datos faltantes para algunos pacientes y tamaños relativamente pequeños de algunos subgrupos.CONCLUSIONES:Las características clínicas del cáncer de colon deficiente en reparación de desajustes varían con la etiología de la inestabilidad de microsatélites, y sus características moleculares varían con la proteína de reparación de desajustes afectada. Vea Resumen de video en http://links.lww.com/DCR/B984 . (Traducción-Dr. Felipe Bellolio ).

Implementation of a standardized clinical pathway in a dedicated posterior urethral valves clinic: short-term outcomes.

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.

Sensitisation of cancer cells to radiotherapy by serine and glycine starvation.

BACKGROUND: Cellular metabolism is an integral component of cellular adaptation to stress, playing a pivotal role in the resistance of cancer cells to various treatment modalities, including radiotherapy. In response to radiotherapy, cancer cells engage antioxidant and DNA repair mechanisms which mitigate and remove DNA damage, facilitating cancer cell survival. Given the reliance of these resistance mechanisms on amino acid metabolism, we hypothesised that controlling the exogenous availability of the non-essential amino acids serine and glycine would radiosensitise cancer cells. METHODS: We exposed colorectal, breast and pancreatic cancer cell lines/organoids to radiation in vitro and in vivo in the presence and absence of exogenous serine and glycine. We performed phenotypic assays for DNA damage, cell cycle, ROS levels and cell death, combined with a high-resolution untargeted LCMS metabolomics and RNA-Seq. RESULTS: Serine and glycine restriction sensitised a range of cancer cell lines, patient-derived organoids and syngeneic mouse tumour models to radiotherapy. Comprehensive metabolomic and transcriptomic analysis of central carbon metabolism revealed that amino acid restriction impacted not only antioxidant response and nucleotide synthesis but had a marked inhibitory effect on the TCA cycle. CONCLUSION: Dietary restriction of serine and glycine is a viable radio-sensitisation strategy in cancer.

Survival After Induction Chemotherapy and Chemoradiation Versus Chemoradiation and Adjuvant Chemotherapy for Locally Advanced Rectal Cancer.

BACKGROUND: Total neoadjuvant therapy (TNT) improves tumor response in locally advanced rectal cancer (LARC) patients compared to neoadjuvant chemoradiotherapy alone. The effect of TNT on patient survival has not been fully investigated. MATERIALS AND METHODS: This was a retrospective case series of patients with LARC at a comprehensive cancer center. Three hundred and eleven patients received chemoradiotherapy (chemoRT) as the sole neoadjuvant treatment and planned adjuvant chemotherapy, and 313 received TNT (induction fluorouracil and oxaliplatin-based chemotherapy followed by chemoradiotherapy in the neoadjuvant setting). These patients then underwent total mesorectal excision or were entered in a watch-and-wait protocol. The proportion of patients with complete response (CR) after neoadjuvant therapy (defined as pathological CR or clinical CR sustained for 2 years) was compared by the χ2 test. Disease-free survival (DFS), local recurrence-free survival, distant metastasis-free survival, and overall survival were assessed by Kaplan-Meier analysis and log-rank test. Cox regression models were used to further evaluate DFS. RESULTS: The rate of CR was 20% for chemoRT and 27% for TNT (P=.05). DFS, local recurrence-free survival, metastasis-free survival, and overall survival were no different. Disease-free survival was not associated with the type of neoadjuvant treatment (hazard ratio [HR] 1.3; 95% confidence interval [CI] 0.93-1.80; P = .12). CONCLUSIONS: Although TNT does not prolong survival than neoadjuvant chemoradiotherapy plus intended postoperative chemotherapy, the higher response rate associated with TNT may create opportunities to preserve the rectum in more patients with LARC.

ß3-Adrenoceptor Agonist for the Treatment of Bladder Dysfunction in Children: A Systematic Review and Meta-Analysis.

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%‒5.9%), constipation (3.5%‒5.7%), rhinitis/nasopharyngitis (1.7%‒5.8%) and blurred vision (1.7%‒2.9%). 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.

Adoption of Organ Preservation and Surgeon Variability for Patients with Rectal Cancer Does Not Correlate with Worse Survival.

BACKGROUND AND OBJECTIVES: Watch-and-wait is variably adopted by surgeons and the impact of this on outcomes is unknown. We compared the disease-free survival and organ preservation rates of locally advanced rectal cancer patients treated by expert colorectal surgeons at a comprehensive cancer center. METHODS: This study included retrospective data on patients diagnosed with stage II/III rectal adenocarcinoma from January 2013 to June 2017 who initiated neoadjuvant therapy (either with chemoradiation, chemotherapy, or a combination of both) and were treated by an expert colorectal surgeon. RESULTS: Overall, 444 locally advanced rectal cancer patients managed by five surgeons were included. Tumor distance from the anal verge, type of neoadjuvant therapy, and organ preservation rates varied by treating surgeon. There was no difference in disease-free survival after stratifying by the treating surgeon (p = 0.2). On multivariable analysis, neither the type of neoadjuvant therapy nor the treating surgeon was associated with disease-free survival. CONCLUSIONS: While neoadjuvant therapy type and organ preservation rates varied among surgeons, there were no meaningful differences in disease-free survival. These data suggest that among expert colorectal surgeons, differing thresholds for selecting patients for watch-and-wait do not affect survival.

Vascular hitch for paediatric pelvi-ureteric junction obstruction with crossing vessels: institutional analysis and systematic review with meta-analysis.

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.

Personalized application of machine learning algorithms to identify pediatric patients at risk for recurrent ureteropelvic junction obstruction after dismembered pyeloplasty.

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.

Hospitalization following pediatric kidney transplantation: An international comparison among a Canadian pediatric transplant center, North American Pediatric Renal Trials and Collaborative Studies, and Cooperative European Pediatric Renal Transplant Initiative registry data.

BACKGROUND: There are several databases across the world that collect pediatric KT data. We compare the hospitalization outcomes for pediatric KT recipients from a large Canadian transplant center (SickKids database; The Hospital for Sick Children Kidney Transplantation Institutional Database), United States (NAPRTCS), and Europe (CERTAIN registry). METHODS: An institutional retrospective review of KT was performed between 2000 and 2015. Baseline characteristics, duration of initial hospitalization/readmission at 1-5 and 6- to 11-month posttransplant, and 1-year graft survival data were collected. Corresponding data from the NAPRTCS 2014 Annual Transplant Report and CERTAIN registry were compared. RESULTS: Posttransplant, patients from NAPRTCS had the shortest duration of hospitalization within the first month (10.4 days, SE 0.2), followed by SickKids (20.3 days, SE 0.7) and CERTAIN (25.5 days, SE 0.7). For both living and deceased donor populations, patients from SickKids were most likely to be hospitalized at 1- to 5-month posttransplant (82.4% [89/108]; 72.1% [98/136]), followed by Europe (52.1% [198/380]; 61.6% [501/813]) and United States (45.4% [2379/5241]; 51.4% [2517/4896]). Patients from Europe were most likely to be hospitalized at 6- to 12-month posttransplant (42.1% [160/380]; 51.7% [420/813]), followed by SickKids (35.2% [38/108]; 37.5% [51/136]) and United States (28.3% [1387/4901]; 31.6% [1411/4465]). Across all databases, the most commonly addressed issues during readmissions were infectious complications. CONCLUSION: The differences observed in this investigation may reflect the local reimbursement models, resources for outpatient management, and practice variations across a large Canadian transplant center, United States, and European countries.

Omental Procedures During Peritoneal Dialysis Insertion: A Systematic Review and Meta-Analysis.

OBJECTIVES: Peritoneal dialysis (PD) is an option for ultrafiltration for patients with end-stage renal disease. Once placed, PD catheters may malfunction often due to omental wrapping. Omental procedures such as omentectomy and omentopexy may reduce this risk. This investigation aims to perform a systematic review and meta-analysis of the literature on the role of omental procedures on PD catheter insertions. METHODS: Following protocol registration on PROSPERO (CRD42020218950), a systematic review was performed in accordance with the Cochrane Collaboration. A literature search was performed in February 2021 across Medline, EMBASE, Scopus, and Cochrane Library. Records with patients who underwent PD catheter insertion with and without omental manipulation were included. The records underwent screening, full-text review, and data extraction. Study qualities were assessed using RoBINS-I and RoB2. Effect estimates were extracted as risk ratios and corresponding 95% confidence intervals (CI) were pooled using inverse variance method with random-effect model. RESULTS: Of 510 records identified, 15 studies were included in the meta-analysis (1 RCT, 2 prospective, 12 retrospective). With omental procedures, there was decreased the likelihood of failure requiring removal of PD catheter (RR 0.47, 95% CI 0.38, 0.58) and PD catheter obstruction (RR 0.23, 95% CI 0.14, 0.39); there was no difference in likelihood of catheter malposition or migration (RR 0.87, 95% CI 0.23, 3.29) or peritonitis (RR 0.74, 95% CI 0.40, 1.35). CONCLUSION: Based on the current low to moderate quality of evidence, omental manipulation at the time of PD catheter insertion confers benefits of decreased obstruction and failure requiring removal.

Comparison of continuous and interrupted suture techniques in pyeloplasty: a systematic review and meta-analysis.

Pelvi-ureteric anastomosis is a critical step to ensure good outcome of pyeloplasty. Continuous suturing technique, especially for laparoscopic surgeries, may offer faster operative time while allowing water-tight anastomosis and remains an alternative to interrupted suturing technique. There has been mixed data on comparison of outcomes of continuous and interrupted suturing techniques. This systematic review and meta-analysis aim to assess the outcomes of pyeloplasty based on continuous and interrupted suturing techniques. Following protocol registration on PROSPERO (CRD42021269706), a systematic review was performed in accordance with Cochrane Collaboration. A literature search was performed in September 2021 across Medline, EMBASE, Scopus, Cochrane Library, and ClinicalTrials.gov. Records comparing pyeloplasty outcomes between continuous and interrupted suture techniques were included. Five studies were identified for inclusion (2 prospective, 3 retrospective). Three studies involved pediatric patients. Three studies exclusively assessed laparoscopic technique. Four outcomes were meta-analyzed: operative time, length of stay, complications, and pyeloplasty failure. Interrupted sutures had longer OR time (mean difference 33.14 min [95% CI 29.35-36.94], p < 0.0001) and length of stay (mean difference 1.08 days [95% CI 0.84-1.32], p < 0.0001). However, there were similar complication (OR 1.73 [95% CI 0.98-3.06], p = 0.06) and failure rates (OR 1.21 [95% CI 0.43-3.43], p = 0.71) between the two suture types. The overall risk of bias in the studies was high. While limited by the number of studies available, continuous sutures for pelvi-ureteric anastomosis appear to confer benefits of faster operative time and decreased length of stay without increasing complication rates or failures.

Impact of native nephrectomy on hypertension outcomes in pediatric kidney transplant recipients: a 10-year institutional experience.

OBJECTIVE: To assess the role native nephrectomy (NN) in hypertension-related outcomes for pediatric patients undergoing renal transplantation (RT). METHODS: Renal transplants (RT) performed at our institution between 2006 and 2015 were reviewed. RT recipients who underwent NN were compared to those who did not. Primary outcomes were hypertension-related: use/number of medications pre-/post-transplant and hypertension-related readmissions. Secondary outcomes were 1-year outcomes of: readmissions, eGFR, Clavien-Dindo classification ≥ 3 complications, and graft loss. RESULTS: 135 patients were evaluated. 24 underwent NN (Group 1) and 111 did not (Group 2). Baseline characteristics were similar between Groups 1 and 2. The majority of NN indications were hypertension (10/39 kidneys) and proteinuria (12/39 kidneys). There were no differences in use/number of anti-hypertensive medications pre- or post-transplant. However, between Group 2 and subgroup of patients who underwent NN for hypertension, a significant difference was seen in medication use/numbers but not post-transplant. Number of readmissions due to hypertension was similar (7.2% vs. 12.5%). The only difference in secondary outcomes was higher readmission rates with bacterial infections for group 1 (45.8% vs. 23.4%, p = 0.041). CONCLUSION: NN, when offered to patients at higher risk of post-RT hypertension, may allow high-risk patients to achieve similar hypertension outcomes as those at lower risk.

Time to event analysis for post-hypospadias repair complications: a single-surgeon experience.

OBJECTIVE: The optimal follow-up duration and frequency following hypospadias repair is unclear within the pediatric urology community. This analysis aims to delineate the time to various complications following primary hypospadias repairs. MATERIALS AND METHODS: A retrospective review of a single-surgeon hypospadias database over 2001-2017 was performed. The primary outcome of the study was determining the significant factors leading to complications over time. As a secondary outcome, subgroup analysis was performed to determine whether there was a significant difference in time to detecting voiding-related complications (fistula, stricture/stenosis, and diverticulum) based on age. RESULTS: Eight hundred and thirty-two patients were identified. The complication rates for distal, midshaft, and proximal hypospadias were 17.9% (112/625), 36.7% (40/109), and 55.1% (49/89), respectively (p < 0.0001). Survival analysis using Kaplan-Meier curves showed significance in three variables for time to complication: hypospadias severity (p < 0.0001), technique (p < 0.0001), and penile curvature > 30° (p < 0.0001). Cox-regression analysis showed that hypospadias severity and penile curvature were significantly contributing to the model (p < 0.0001, p = 0.044). Patients with proximal hypospadias and penile curvature developed complications earlier than other patients, with approximately 95% of complications occurring within 2 years. CONCLUSIONS: Complications from repair of proximal hypospadias with curvature > 30° are likely to occur within 2 years of surgery. Surgeons may consider more frequent follow-up within the first 2 years of surgery to detect these complications.