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.

Application of STREAM-URO and APPRAISE-AI reporting standards for artificial intelligence studies in pediatric urology: A case example with pediatric hydronephrosis.

INTRODUCTION: Artificial intelligence (AI) and machine learning (ML) in pediatric urology is gaining increased popularity and credibility. However, the literature lacks standardization in reporting and there are areas for methodological improvement, which incurs difficulty in comparison between studies and may ultimately hurt clinical implementation of these models. The "STandardized REporting of Applications of Machine learning in UROlogy" (STREAM-URO) framework provides methodological instructions to improve transparent reporting in urology and APPRAISE-AI in a critical appraisal tool which provides quantitative measures for the quality of AI studies. The adoption of these will allow urologists and developers to ensure consistency in reporting, improve comparison, develop better models, and hopefully inspire clinical translation. METHODS: In this article, we have applied STREAM-URO framework and APPRAISE-AI tool to the pediatric hydronephrosis literature. By doing this, we aim to describe best practices on ML reporting in urology with STREAM-URO and provide readers with a critical appraisal tool for ML quality with APPRAISE-AI. By applying these to the pediatric hydronephrosis literature, we provide some tutorial for other readers to employ these in developing and appraising ML models. We also present itemized recommendations for adequate reporting, and critically appraise the quality of ML in pediatric hydronephrosis insofar. We provide examples of strong reporting and highlight areas for improvement. RESULTS: There were 8 ML models applied to pediatric hydronephrosis. The 26-item STREAM-URO framework is provided in Appendix A and 24-item APPRAISE-AI tool is provided in Appendix B. Across the 8 studies, the median compliance with STREAM-URO was 67 % and overall study quality was moderate. The highest scoring APPRAISE-AI domains in pediatric hydronephrosis were clinical relevance and reporting quality, while the worst were methodological conduct, robustness of results, and reproducibility. CONCLUSIONS: If properly conducted and reported, ML has the potential to impact the care we provide to patients in pediatric urology. While AI is exciting, the paucity of strong evidence limits our ability to translate models to practice. The first step toward this goal is adequate reporting and ensuring high quality models, and STREAM-URO and APPRAISE-AI can facilitate better reporting and critical appraisal, respectively.

Organ Preservation and Survival by Clinical Response Grade in Patients With Rectal Cancer Treated With Total Neoadjuvant Therapy: A Secondary Analysis of the OPRA Randomized Clinical Trial.

Importance: Assessing clinical tumor response following completion of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer is paramount to select patients for watch-and-wait treatment. Objective: To assess organ preservation (OP) and oncologic outcomes according to clinical tumor response grade. Design, Setting, and Participants: This was secondary analysis of the Organ Preservation in Patients with Rectal Adenocarcinoma trial, a phase 2, nonblinded, multicenter, randomized clinical trial. Randomization occurred between April 2014 and March 2020. Eligible participants included patients with stage II or III rectal adenocarcinoma. Data analysis occurred from March 2022 to July 2023. Intervention: Patients were randomized to induction chemotherapy followed by chemoradiation or chemoradiation followed by consolidation chemotherapy. Tumor response was assessed 8 (±4) weeks after TNT by digital rectal examination and endoscopy and categorized by clinical tumor response grade. A 3-tier grading schema that stratifies clinical tumor response into clinical complete response (CCR), near complete response (NCR), and incomplete clinical response (ICR) was devised to maximize patient eligibility for OP. Main Outcomes and Measures: OP and survival rates by clinical tumor response grade were analyzed using the Kaplan-Meier method and log-rank test. Results: There were 304 eligible patients, including 125 patients with a CCR (median [IQR] age, 60.6 [50.4-68.0] years; 76 male [60.8%]), 114 with an NCR (median [IQR] age, 57.6 [49.1-67.9] years; 80 male [70.2%]), and 65 with an ICR (median [IQR] age, 55.5 [47.7-64.2] years; 41 male [63.1%]) based on endoscopic imaging. Age, sex, tumor distance from the anal verge, pathological tumor classification, and clinical nodal classification were similar among the clinical tumor response grades. Median (IQR) follow-up for patients with OP was 4.09 (2.99-4.93) years. The 3-year probability of OP was 77% (95% CI, 70%-85%) for patients with a CCR and 40% (95% CI, 32%-51%) for patients with an NCR (P < .001). Clinical tumor response grade was associated with disease-free survival, local recurrence-free survival, distant metastasis-free survival, and overall survival. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, most patients with a CCR after TNT achieved OP, with few developing tumor regrowth. Although the probability of tumor regrowth was higher for patients with an NCR compared with patients with a CCR, a significant proportion of patients achieved OP. These findings suggest the 3-tier grading schema can be used to estimate recurrence and survival outcomes in patients with locally advanced rectal cancer who receive TNT. Trial Registration: ClinicalTrials.gov Identifier: NCT02008656.

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.

Trends in Management of Fetuses with Suspected Lower Urinary Tract Obstruction (LUTO): A High-Risk Fetal and Pediatric Center Experience in a Universal-Access-to-Care System.

INTRODUCTION: Neonates with lower urinary tract obstruction (LUTO) experience high morbidity and mortality associated with the development of chronic kidney disease. The prenatal detection rate for LUTO is less than 50%, with late or missed diagnosis leading to delayed management and long-term sequelae in the remainder. We aimed to explore the trends in prenatal detection and management at a high-risk fetal center and determine if similar trends of postnatal presentations were noted for the same period. METHODS: Prenatal and postnatal LUTO databases from a tertiary fetal center and its associated pediatric center between 2009 and 2021 were reviewed, capturing maternal age, gestational age (GA) at diagnosis, and rates of termination of pregnancy (TOP). Time series analysis using autocorrelation was performed to investigate time trend changes for prenatally suspected and postnatally confirmed LUTO cases. RESULTS: A total of 161 fetuses with prenatally suspected LUTO were identified, including 78 terminations. No significant time trend was found when evaluating the correlation between time periods, prenatal suspicion, and postnatal confirmation of LUTO cases (Durbin-Watson [DW] = 1.99, p = 0.3641 and DW = 2.86, p = 0.9113, respectively). GA at referral was 20.0 weeks (interquartile range [IQR] 12, 35) and 22.0 weeks (IQR 13, 37) for TOP and continued pregnancies (p < 0.0001). GA at initial ultrasound was earlier in terminated fetuses compared to continued (20.0 [IQR 12, 35] weeks vs. 22.5 [IQR 13, 39] weeks, p < 0.0001). While prenatal LUTO suspicion remained consistently higher than postnatal presentations, the rates of postnatal presentations and terminations remained stable during the study years (p = 0.7913 and 0.2338), as were GA at TOP and maternal age at diagnosis (p = 0.1710 and 0.1921). CONCLUSION: This study demonstrated that more severe cases of LUTO are referred earlier and are more likely to undergo TOP. No significant trend was detected between time and prenatally suspected or postnatally confirmed LUTO, highlighting the need for further studies to better delineate factors that can increase prenatal detection.

Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.To assess long-term risk of local tumor regrowth, we report updated organ preservation rate and oncologic outcomes of the OPRA trial (ClinicalTrials.gov identifier: NCT02008656). Patients with stage II/III rectal cancer were randomly assigned to receive induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Patients who achieved a complete or near-complete response after finishing treatment were offered watch-and-wait (WW). Total mesorectal excision (TME) was recommended for those who achieved an incomplete response. The primary end point was disease-free survival (DFS). The secondary end point was TME-free survival. In total, 324 patients were randomly assigned (INCT-CRT, n = 158; CRT-CNCT, n = 166). Median follow-up was 5.1 years. The 5-year DFS rates were 71% (95% CI, 64 to 79) and 69% (95% CI, 62 to 77) for INCT-CRT and CRT-CNCT, respectively (P = .68). TME-free survival was 39% (95% CI, 32 to 48) in the INCT-CRT group and 54% (95% CI, 46 to 62) in the CRT-CNCT group (P = .012). Of 81 patients with regrowth, 94% occurred within 2 years and 99% occurred within 3 years. DFS was similar for patients who underwent TME after restaging (64% [95% CI, 53 to 78]) and patients in WW who underwent TME after regrowth (64% [95% CI, 53 to 78]; P = .94). Updated analysis continues to show long-term organ preservation in half of the patients with rectal cancer treated with total neoadjuvant therapy. In patients who enter WW, most cases of tumor regrowth occur in the first 2 years.

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.

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.

Compliance and Toxicity of Total Neoadjuvant Therapy for Rectal Cancer: A Secondary Analysis of the OPRA Trial.

PURPOSE: Patients with locally advanced rectal cancer treated with total neoadjuvant therapy (TNT) may achieve organ preservation without a compromise to oncologic outcomes. However, reports on patient compliance with TNT and with treatment-related toxicities are limited. METHODS AND MATERIALS: The OPRA trial assessed organ preservation rates and oncologic outcomes in patients with clinical stage II/III rectal adenocarcinoma randomized to induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Systemic chemotherapy consisted of 8 cycles (16 weeks) of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or 5 cycles (15 weeks) of capecitabine and oxaliplatin (CAPEOX). Patients received >4500 cGy of radiation with sensitizing capecitabine or fluorouracil. In this report, we compare compliance and treatment-related toxicity in patients receiving INCT-CRT versus CRT-CNCT. Additionally, we evaluate the association of compliance to chemotherapy, compliance to chemoradiation, and toxicity with organ preservation and disease-free survival (DFS). RESULTS: Of the 324 patients randomized, fewer patients started chemoradiation in the INCT-CRT group compared with the CRT-CNCT group (93% vs 98%, P = .03), and fewer patients started systemic chemotherapy in the CRT-CNCT group compared with the INCT-CRT group (94% vs 99%, P = .04). Order of TNT did not affect the ability to complete all intended cycles of FOLFOX (86% INCT-CRT vs 83% CRT-CNCT, P = .60) or CAPEOX (74% INCT-CRT vs 77% CRT-CNCT, P = .80). A total of 97% of INCT and 98% of CRT-CNCT patients received >4500 cGy radiation (P = .93). Sixty-four patients (41%) treated with INCT-CRT and 57 CRT-CNCT patients (34%) experienced a grade 3+ adverse event (P = .30). Compliance and toxicity were not associated with organ preservation or DFS. CONCLUSIONS: We identified only minor differences in treatment compliance between patients treated with INCT-CRT and CRT-CNCT. No difference in adverse events was observed between groups. Treatment compliance and toxicity did not correlate with organ preservation rates or DFS.

Development and use of machine learning models for prediction of male sling success A proof-of-concept institutional evaluation.

INTRODUCTION: For mild to moderate male stress urinary incontinence (SUI), transobturator male slings remain an effective option for management. We aimed to use a machine learning (ML )-based model to predict those who will have a long-term success in managing SUI with male sling. METHODS: All transobturator male sling cases from August 2006 to June 2012 by a single surgeon were reviewed. Outcome of interest was defined as 'cure': complete dryness with 0 pads used, without the need for additional procedures. Clinical variables included in ML models were: number of pads used daily, age, height, weight, race, incontinence type, etiology of incontinence, history of radiation, smoking, bladder neck contracture, and prostatectomy. Model performance was assessed using area under receiver operating characteristic curve (AUROC), area under precision-recall curve (AUPRC), and F1-score. RESULTS: A total of 181 patients were included in the model. The mean followup was 56.4 months (standard deviation [SD ] 41.6). Slightly more than half (53.6%, 97/181) of patients had procedural success. Logistic regression, K-nearest neighbor (KNN ), naive Bayes, decision tree, and random forest models were developed using ML. KNN model had the best performance, with AUROC of 0.759, AUPRC of 0.916, and F1-score of 0.833. Following ensemble learning with bagging and calibration, KNN model was further improved, with AUROC of 0.821, AUPRC of 0.921, and F-1 score of 0.848. CONCLUSIONS: ML-based prediction of long-term transobturator male sling is feasible. The low numbers of patients used to develop the model prompt further validation and development of the model but may serve as a decision-making aid for practitioners in the future.

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.

ChatGPT and large language model (LLM) chatbots: The current state of acceptability and a proposal for guidelines on utilization in academic medicine.

INTRODUCTION: There is currently no clear consensus on the standards for using large language models such as ChatGPT in academic medicine. Hence, we performed a scoping review of available literature to understand the current state of LLM use in medicine and to provide a guideline for future utilization in academia. MATERIALS AND METHODS: A scoping review of the literature was performed through a Medline search on February 16, 2023 using a combination of keywords including artificial intelligence, machine learning, natural language processing, generative pre-trained transformer, ChatGPT, and large language model. There were no restrictions to language or date of publication. Records not pertaining to LLMs were excluded. Records pertaining to LLM ChatBots and ChatGPT were identified and evaluated separately. Among the records pertaining to LLM ChatBots and ChatGPT, those that suggest recommendations for ChatGPT use in academia were utilized to create guideline statements for ChatGPT and LLM use in academic medicine. RESULTS: A total of 87 records were identified. 30 records were not pertaining to large language models and were excluded. 54 records underwent a full-text review for evaluation. There were 33 records related to LLM ChatBots or ChatGPT. DISCUSSION: From assessing these texts, five guideline statements for LLM use was developed: (1) ChatGPT/LLM cannot be cited as an author in scientific manuscripts; (2) If use of ChatGPT/LLM are considered for use in academic work, author(s) should have at least a basic understanding of what ChatGPT/LLM is; (3) Do not use ChatGPT/LLM to produce entirety of text in manuscripts; humans must be held accountable for use of ChatGPT/LLM and contents created by ChatGPT/LLM should be meticulously verified by humans; (4) ChatGPT/LLMs may be used for editing and refining of text; (5) Any use of ChatGPT/LLM should be transparent and should be clearly outlined in scientific manuscripts and acknowledged. CONCLUSION: Future authors should remain mindful of the potential impact their academic work may have on healthcare and continue to uphold the highest ethical standards and integrity when utilizing ChatGPT/LLM.

Assessing the Utility of Tamsulosin in Delaying Progression to Clean Intermittent Catheterization and End-stage Renal Disease in Patients With Posterior Urethral Valves: Are We Postponing the Inevitable?

OBJECTIVE: To assess whether tamsulosin may aid emptying of the lower urinary tract in posterior urethral valves patients, mitigating the likelihood of progressing to clean intermittent catheterization (CIC) or need for renal replacement therapy. METHODS: We reviewed a prospective institutional database containing posterior urethral valves patients treated between January 2000 and January 2022. After assessing baseline characteristics, Kaplan-Meier survival curves and log-rank tests were generated to assess differences in clinically significant outcomes (progression to CIC, dialysis, or kidney transplantation) between those prescribed tamsulosin and those who were not. RESULTS: A total of 179 patients were included. Fifty-nine patients received tamsulosin prior to initiation of CIC (group 1), and 120 did not (group 2). The baseline characteristics were similar between the two groups, except for anticholinergic use (tamsulosin group - 35/59 vs no tamsulosin - 32/120, P < .001). The median age at tamsulosin initiation was 26.0 months (IQR 15.5-48.6) and the median time from initiation of tamsulosin to progression to CIC was 52.6 months (IQR 10.1-69.3). Kaplan-Meier survival curves showed that patients on tamsulosin were less likely to progress to CIC (P = .021), however, there was no difference in progression to dialysis or kidney transplantation. A Cox-regression analysis controlling for baseline characteristics, including age, anticholinergic use, vesicoureteral reflux severity, and CKD stage at 1-year of life, showed a consistent effect of tamsulosin in delaying progression to CIC (HR 0.444 95%CI 0.218-0.902, P = .025). CONCLUSION: While tamsulosin may delay CIC, it does not appear to delay progression to end-stage renal disease. Additional studies exploring specific patient factors are required to determine the timing and subset who may benefit the most from tamsulosin.

Does VURD syndrome impact voiding efficiency in posterior urethral valves?

INTRODUCTION: There is debate regarding the effect of VURD syndrome, consisting of vesicoureteral reflux (VUR) and ipsilateral kidney dysplasia, on long-term outcomes in boys with posterior urethral valve (PUV). Here, we assessed whether VURD syndrome played a "protective" role on long-term bladder outcomes and voiding efficiency in boys with PUV. MATERIALS AND METHOD: A retrospective chart review was conducted for toilet-trained children with PUV managed at our institution between 2000 and 2022, only excluding cases without recorded uroflowmetry studies. Patients were stratified by VUR status and by the presence of VURD syndrome (high-grade VUR + ipsilateral kidney dysplasia). Outcomes included initial and final uroflowmetry parameters, and initiation of clean-intermittent catheterization (CIC). RESULTS: We identified a total of 101 patients who met study inclusion criteria, with an overall median follow-up of 114 months (IQR 67, 169). The median age of first and last uroflowmetry was 57 months (IQR 48, 82) and 120 months (IQR 89, 160), respectively. Patients with VURD syndrome had similar flow velocity, post-void residuals, and bladder voiding efficiency to other PUV patients at last follow-up uroflowmetry. On survival analysis, patients with VURD syndrome had no significant difference in risk of requiring CIC compared to patients without pop-offs (p = 0.06). DISCUSSION: Like more contemporary studies on pressure pop-offs, we show that this population is not at higher risk of poorer voiding and intermittent catheterization than others. VURD syndrome does not confer protection against poorer bladder function. Instead, our study suggests an independent association between kidney dysplasia and bladder outcomes which requires further attention. CONCLUSIONS: Among boys with PUV, VURD syndrome was not associated with significantly different uroflowmetry findings or rates of CIC by last follow-up.

Primary ablation versus urinary diversion in posterior urethral valve: Systematic review and meta-analysis.

PURPOSE: To determine differences in long-term kidney and bladder outcomes in boys with posterior urethral valves (PUV) managed by a primary valve ablation or primary urinary diversion. MATERIALS AND METHODS: A systematic search was performed in March 2021. Comparative studies were evaluated according to Cochrane collaboration recommendations. Assessed measures included kidney outcomes (chronic kidney disease, end-stage renal disease, kidney function) and bladder outcomes. Odds ratios (OR) and mean difference (MD) with 95% confidence interval (CI) were extrapolated from available data for quantitative synthesis. Random-effects meta-analysis and meta-regression were performed according to study design, and potential covariates were assessed with subgroup analysis. The systematic review was prospectively registered on PROSPERO (CRD42021243967). RESULTS: Thirty unique studies describing 1547 boys with PUV were included in this synthesis. Overall effect estimates demonstrate that patients undergoing primary diversion have significantly increased odds of developing renal insufficiency [OR 0.60, 95% CI 0.44, 0.80; p < 0.001]. However, when adjusting for baseline kidney function between intervention groups, there was no significant difference in long term kidney outcomes [p = 0.09, 0.35], or the development of bladder dysfunction or requiring clean-intermittent catheterization with primary ablation rather than diversion [OR 0.89, 95% CI 0.49, 1.59; p = 0.68]. CONCLUSIONS: Current low-quality evidence suggests that medium-term kidney outcomes in children are similar between primary ablation and primary diversion after adjusting for baseline kidney function, while bladder outcomes are highly heterogenous. Further research with covariate control is warranted to investigate sources of heterogeneity. LEVEL OF EVIDENCE: Level III.

Assessing the role of upside-down (inverted) renal allografts in pediatric kidney transplantation: a propensity-score matched analysis.

OBJECTIVE: To evaluate the implications of inverted (upside-down) kidney configuration in pediatric renal transplantation employing a comparative analysis with at least 1-year follow-up. METHODS: Patients who underwent kidney transplantation at our institution between January 2011 and June 2021 were reviewed. Patients who had an inverted renal transplant were propensity-score matched (PSM) in 1:2 ratio with those who had traditional orientation transplant. The outcomes assessed included delayed graft function (DGF), urine leak, lymphocele, rejection, allograft calculus, ureteric stricture, and nadir creatinine. RESULTS: A total of 24 patients with inverted orientation were identified. Following PSM, 41 patients were matched, with exclusions due to incompatible propensity scores. Baseline characteristics were appropriately matched, and no significant differences were noted between the two groups. There were no differences in: delayed graft function (0/24 vs. 3/41, p = 0.290), urine leak (3/24 vs. 2/41, p = 0.350), lymphocele (2/24 vs. 4/41, p = 1.000), rejection (3/24 vs. 5/41, p = 1.000), graft calculus (2/24 vs. 0/41, p = 0.133), and ureteric stricture (0/24 vs. 2/41, p = 0.527). The two cases of renal calculus seen in the inverted transplant group occurred on post-operative day 13 and 1584, both were managed without complications. There was no difference in nadir creatinine (median 34umol/L IQR23-57 vs. 35 umol/L IQR 20-50, p = 0.624) or time to nadir creatinine (8 days IQR 6-12 vs. 8 days IQR 7-28, p = 0.315). CONCLUSION: Inverting a renal allograft does not appear to significantly contribute to increased risk of post-operative adverse outcomes. When aiming to achieve the best anatomical placement to secure a comfortable vascular anastomosis, inverting the allograft should be considered.

Nephron-sparing surgery for renal cell carcinoma in children and young adults: A systematic review.

OBJECTIVE: To determine the patient characteristics and role of nephron-sparing surgery (NSS) in the treatment of children and young adults with renal cell carcinoma (RCC). METHODS: A systematic search of Embase, MEDLINE, and Scopus databases was conducted in December 2021 according to Cochrane collaboration recommendations. All included manuscripts were assessed for patient characteristics and all reported outcomes for patients undergoing partial nephrectomy (PN), and radical nephrectomy (RN) outcomes were abstracted as a comparison group. Primary outcomes included surgical outcomes, overall survival, kidney outcomes. Outcomes were pooled with weighted mean and ranges. Meta-analysis was not performed given study quality. This systematic review was prospectively registered on PROSPERO (CRD42022300261). RESULTS: We found a total of 16 studies describing 119 and 559 unique patients undergoing PN and RN, respectively, with a mean age of 12.2 years and mean follow-up of 59.1 months. The mean tumor size for patients undergoing PN was 3.5 cm. Of the 113 patients undergoing PN with available data, 109 were alive at follow-up (98%). No studies reported long-term kidney outcomes, and four studies reported surgical outcomes. All studies had at least moderate risk of bias. CONCLUSIONS: The use of NSS in children and young adults with RCC is feasible in selected patients. However, small sample sizes, confounding, and low study quality limit clinical recommendation on NSS in this population. There are significant opportunities for future research on the use of NSS in RCC, especially with systematic reporting of oncological, kidney, and surgical outcomes.

The effect of primary urinary diversion on kidney function in posterior urethral valve: A matched comparison.

OBJECTIVE: To determine long-term kidney outcomes in boys with posterior urethral valve (PUV) undergoing either primary valve ablation or urinary diversion with matched baseline kidney function. METHODS: After retrospective review of patients managed for PUV at our institution, propensity score matched analysis was conducted using nadir serum creatinine with logistic regression analysis. Nearest neighbor matching was used to allocate boys to primary urinary diversion and primary ablation groups. Primary outcomes included kidney function by creatinine or estimated glomerular filtration rate, chronic kidney disease, and end-stage renal disease. Comparative statistics by odds ratio (OR) and hazard ratios on survival analysis were calculated. RESULTS: A total of 21 boys undergoing primary diversion were matched with 42 boys undergoing ablation using nadir serum creatinine and follow-up time with a median follow-up of 4.8 years. After matching, there was no significant difference in last follow-up kidney function by creatinine (P = .99) or estimated glomerular filtration rate (P = .98). Primary diversion was not associated with increased likelihood of developing chronic kidney disease stage 3 (OR 1.33; P = .31) or end-stage renal disease (OR 1.88; P = .35 and hazard ratios 1.85; P = .30) compared to primary ablation. CONCLUSIONS: Our propensity matched study suggests that long-term kidney function and kidney outcomes are similar between primary ablation and primary diversion after adjusting for baseline kidney function in boys with PUV.

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 ).