Are children with food allergies more likely to have lower urinary tract symptoms? A case-control study.

INTRODUCTION: There are multiple historic reports linking lower urinary tract symptoms (LUTS) in children with food allergies (FA), but contemporary studies are sparse. The objective of this study was to evaluate a potential link between FA and LUTS in the pediatric population. We hypothesized that children with FAs are more likely to have LUTS. MATERIALS AND METHODS: After local IRB approval, pediatric patients (6-17 years [y]) with FAs proven by positive skin prick and/or serum IgE testing were invited to participate. A control group of pediatric patients without FAs was also recruited. All families/legal guardians signed informed consent, and all children signed written assent. Each participant filled out the Vancouver Symptom Score (VSS), a validated questionnaire for dysfunctional elimination syndrome, and the Pediatric Incontinence Questionnaire (PinQ), a validated quality of life assessment for children with bladder dysfunction. Demographic and clinical information were obtained retrospectively. RESULTS: From 2019-2020, 26 children with FAs and 57 without agreed to participate. Mean age was 9.3 y (IQR 7.9 y-13.5 y). There were no differences in gender, age, or race between the two cohorts. There were no significant differences between the two groups in mean VSS score or mean PinQ score. Four children with FAs (15%) and 15 children without (26%) had VSS score ≥ 11 (p = 0.339), indicating dysfunctional elimination. The median PinQ score was 0 (IQR 0-2) in both cohorts. CONCLUSIONS: This study did not identify an association between FAs and LUTS in a population of pediatric patients with laboratory proven FAs.

Understanding factors influencing primary treatment with intradetrusor onabotulinumtoxinA versus augmentation cystoplasty in patients with spina bifida.

PURPOSE: Surgical interventions in the urologic management of children with neurogenic bladder secondary to spina bifida aim to preserve upper tract function, prevent urinary tract infections, and optimize quality of life. However, since the introduction of intravesical onabotulinumtoxinA (Botox) in the management of these patients, the indications for choosing Botox over augmentation cystoplasty (AC) remain undefined. The objective of this study was to determine which factors lead patients to undergo Botox versus AC as a primary surgical treatment after failing medical management. METHODS: We retrospectively reviewed the records of pediatric patients with myelomeningocele undergoing either primary Botox or primary AC at our institution between 2013 and 2018. We recorded demographic and clinical information. We identified 10 important clinical decision-making factors: bladder trabeculation, vesicoureteral reflux, or hydronephrosis on imaging; end-filling pressure (EFP) ≥40 cm H2O, detrusor overactivity, detrusor-sphincter dyssynergia, or reduced capacity on urodynamic studies; physician-perceived bladder hostility; and patient/family desire for continence and independence. The presence of these factors was compared between patients undergoing either primary Botox or primary AC. RESULTS: We identified 14 and 50 myelomeningocele patients who underwent primary AC and primary Botox, respectively. We found no significant differences in age, sex, race, or history of reconstructive surgery (antegrade continence enema or catheterizable channel). For the 10 decision-making factors, desire for independence/continence (p = <0.001) and reduced capacity (p = 0.002) were significantly associated with AC, while trabeculation (p = 0.006), EFP ≥40 cm H2O (p = 0.029), rising slope (p = 0.019), and physician-perceived hostility (p = 0.012) were significantly more common with Botox. CONCLUSIONS: At our institution, quality of life measures prompted AC over objective urodynamic or imaging findings before attempting Botox. These findings support a shared decision-making approach when considering surgical intervention for neurogenic bladder secondary to myelomeningocele.

Gonadal tumors in a contemporary cohort of patients with differences in sex development undergoing surgery - A multi-site study from the Pediatric Urologic Oncology Working Group of the societies for pediatric urology.

BACKGROUND: Disturbances in gonadal development lead to increased risk of gonadal malignancy in some but not all patients with differences in sex development (DSD). However, the natural history of these tumors is poorly described, and the literature remains sparse. OBJECTIVE: The objective of this study was to describe the incidence of germ cell neoplasia in situ (GCNIS) and germ cell tumor (GCT) in a contemporary cohort of patients with DSD undergoing surgery and to provide long-term oncologic outcomes for these patients. STUDY DESIGN: Patients with DSD who have undergone gonadectomy or gonadal biopsy were identified at four institutions. Clinical characteristics, pathology, and treatment details were obtained retrospectively. Patients were stratified into risk categories based on DSD diagnosis. Oncologic treatment and outcomes were recorded. Descriptive statistics are reported using parametric methods. RESULTS: 83 patients were identified. Distribution of diagnoses is summarized in the summary table. 14 (16.9%) patients underwent gonadal biopsy, and 71 (85.5%) patients underwent gonadectomy (50/71 gonadectomies were bilateral). 8/83 (9.6%) patients had GCNIS or GCT (7 GCNIS, 1 GCT). Median age at surgery was 2.95 years (y) (interquartile range [IQR] 0.6-12.2) and 14y (IQR 0.85-16.9) in patients without and with GCNIS/GCT, respectively. All 8 patients with GCNIS/GCT had high or intermediate risk DSD diagnoses (4 mixed gonadal dysgenesis, 3 Turner with Y, 1 partial gonadal dysgenesis). Of the patients with high-risk diagnoses, 8/54 (15%) had GCNIS/GCT. No patient received adjuvant therapy, no patient had a recurrence, and all patients were living with mean follow up 6.4y. DISCUSSION: The risk of gonadal malignancy is heterogeneous in the DSD population and can vary based on DSD diagnosis as well as maturation, testicularization, and location of the gonads. The most recent consensus recommendations on gonadal management emphasize risk stratification and consideration of gonadal surveillance based on gender of rearing, but supporting literature remains sparse. In this contemporary cohort of DSD patients who underwent gonadal surgery, most patients did not have evidence of adverse pathology, all patients with malignant or premalignant pathology had a high/intermediate risk DSD diagnosis, and all patients with GCNIS/GCT were treated with surgery alone without recurrence. CONCLUSIONS: The distribution of patients with premalignant and malignant gonadal pathology and DSD in this cohort aligns with prior literature, and oncologic outcomes were excellent. These data add valuable information to the current literature and highlight the necessity to develop appropriate screening regimens for retained gonads.

Increasing utilization of the TWIST score in workup of patients with acute scrotal pain: Role in diagnosis and risk stratification.

INTRODUCTION: The TWIST score is a 5-component physical examination score used to aid in diagnosis of testicular torsion (TT) and could lessen need for radiologic testing in certain clinical scenarios. OBJECTIVE: TWIST use was not previously widespread at our institution. The primary objective of this quality improvement study was to achieve 100% compliance in TWIST utilization among urology and ED residents and to assess for score concordance between ED and urology assessments. Secondary goals were correlation of TWIST components with need for orchiectomy. METHODS: ED staff were educated about the TWIST score and asked to complete assessment for patients presenting with acute scrotal pain. Simultaneously, an electronic medical record-based dot phrase was introduced for urology trainees to complete an independent TWIST evaluation. Spearman correlation was performed to assess association between ED and Urology TWIST scores. Multivariable logistic regression was performed to assess association of TWIST score components and need for orchiectomy. RESULTS: 103 patients presented to the ED from 3/2018-11/2020 with a complaint of acute scrotal pain; 47 were diagnosed with torsion. As compared to our retrospective cohort, the documentation rate of complete TWIST score components on exam rose from 9% to 98% (P < 0.001) on ED evaluation and 16%-66% on urology evaluation (P < 0.001). Rates of repeat ultrasound for patient's transferred between facilities was similar (58% vs. 63%; p = 0.66) as was median time to OR (160 min vs. 145 min; p = 0.5). Using TWIST cutoff of >5 yielded a specificity of 94.5% for diagnosis of torsion, with corresponding strong correlation between ED and urology scores (rho = 0.71). A firm testicle was noted on urology evaluation in 100% of orchiectomy patients (vs. 61% of salvage patients) with persistent association after controlling for duration of symptoms (OR 28.1; P = 0.016). DISCUSSION: Through two-pronged quality improvement efforts, we significantly improved utilization of the TWIST score by ED and urology staff for workup of patients with acute testicular pain. We confirmed the high sensitivity and specificity of the TWIST score and demonstrated inter-rater reliability between ED and urology assessments. On prospective analysis, testicular firmness on exam was predictive of need for orchiectomy. CONCLUSION: The TWIST score is an accurate diagnostic tool for both ED and urology providers in workup of children with acute scrotal pain, with a normal score essentially ruling out the condition. Future work should aim at minimizing unnecessary testing in patients demonstrated to be at high risk for torsion.

Inhibition of hypoxia-inducible factor-prolyl hydroxylation protects from cyclophosphamide-induced bladder injury and urinary dysfunction.

Disruption of the blood-urine barrier can result in acute or chronic inflammatory bladder injury. Activation of the oxygen-regulated hypoxia-inducible factor (HIF) pathway has been shown to protect mucosal membranes by increasing the expression of cytoprotective genes and by suppressing inflammation. The activity of HIF is controlled by prolyl hydroxylase domain (PHD) dioxygenases, which have been exploited as therapeutic targets for the treatment of anemia of chronic kidney disease. Here, we established a mouse model of acute cyclophosphamide (CYP)-induced blood-urine barrier disruption associated with inflammation and severe urinary dysfunction to investigate the HIF-PHD axis in inflammatory bladder injury. We found that systemic administration of dimethyloxalylglycine or molidustat, two small-molecule inhibitors of HIF-prolyl hydroxylases, profoundly mitigated CYP-induced bladder injury and inflammation as assessed by morphological analysis of transmural edema and urothelial integrity and by measuring tissue cytokine expression. Void spot analysis to examine bladder function quantitatively demonstrated that HIF-prolyl hydroxylase inhibitor administration normalized micturition patterns and protected against CYP-induced alteration of urinary frequency and micturition patterns. Our study highlights the therapeutic potential of HIF-activating small-molecule compounds for the prevention or therapy of bladder injury and urinary dysfunction due to blood-urine barrier disruption.NEW & NOTEWORTHY Disruption of the blood-urine barrier can result in acute or chronic inflammatory bladder injury. Here, we demonstrate that pharmacological inhibition of hypoxia-inducible factor (HIF)-prolyl hydroxylation prevented bladder injury and protected from urinary dysfunction in a mouse model of cyclophosphamide-induced disruption of the blood-urine barrier. Our study highlights a potential role for HIF-activating small-molecule compounds in the prevention or therapy of bladder injury and urinary dysfunction and provides a rationale for future clinical studies.

Functional Analysis and Treatment of Pica on a Preschool Playground.

Appropriate use of function-based assessments and interventions is crucial for improving educational outcomes and ensuring the well-being of children who engage in dangerous problem behaviors such as pica. A function-based assessment was conducted for a child engaging in pica in an inclusive childcare setting. Results suggest pica was maintained by access to adult attention. Function-based interventions were developed, assessed, and shared with the child's teaching team. Follow-up data suggest that his teachers continued to use the intervention and that levels of pica remained low.

Pelvic floor biofeedback therapy in children: Assessment of symptom scores in responders and non-responders.

INTRODUCTION: Pelvic Floor Biofeedback Therapy (PFBT) can be an effective treatment for pediatric lower urinary tract symptoms (LUTS). Due to differing perceptions of efficacy and practice patterns, we sought to further evaluate PFBT in our practice. We hypothesized that PFBT results in quiescence of EMG activity during voiding and improves questionnaire scores in patients with LUTS. METHODS: We retrospectively reviewed all patients undergoing PFBT and refined the analysis to females ≥6 years old with ≥2 sessions with completed voiding questionnaires pre- and post-treatment, active EMG during voiding, with non-neurogenic urinary tract complaints refractory to standard urotherapy. Validated Bladder Bowel Dysfunction (BBD) questionnaires were collected at each visit. Quiescence of EMG activity and changes in BBD score were the primary outcomes. RESULTS: 229 patients underwent ≥1 PFBT session, of which 64 females ≥6 years of age with ≥2 PFBT sessions and completed pre and post PFBT voiding questionnaires were identified. In this group, mean age at PFBT start was 10.1 (6.2-17.0). Patients completed 3.1 sessions (2-6). No difference was seen in post-void residual (PVR) between first and last session (23.8 vs 22.6 mL, P = 0.55). Median questionnaire score decreased from 18 (4-42) before to 13 (2-28) following PFBT (P < 0.0001). Responders, characterized by silencing of the EMG after PFBT, occurred in 31% (20/64). Non-responders were younger (P = 0.007) with higher pre-PFBT questionnaire scores. CONCLUSION: The use of PFBT appears to result in a significant reduction in symptom scores, though quiescence of EMG was observed following therapy in less than 1/3 of patients.

Urologic-Induced Complications of Prophylactic Ureteral Localization Stent Placement for Colorectal Surgery Cases.

PURPOSE: A prophylactic ureteral localization stent (PULSe) placed by urologists aids in intraoperative localization and detection of suspected ureteral injury during complex colorectal surgery (CRS) cases. We evaluated the incidence and management of urologic-induced complications secondary to PULSe placement during CRS cases at a single center. MATERIALS AND METHODS: We performed a retrospective review of all patients who underwent cystoscopy and PULSe placement at the time of CRS over a 12-month period. Bilateral 5 French ×70-cm TigerTail® (Bard Medical Division, Covington, GA) PULSe devices were placed without assistance of routine fluoroscopy. RESULTS: Ninety-nine patients (mean age, 58.1 years; range, 17-88 years) underwent bilateral PULSe placement, with a male:female ratio of 44:55 and a mean body mass index of 26.8 (17.0-38.6) kg/m(2). Mean pre- and postprocedural creatinine levels were 0.91 and 1.01 mg/dL, respectively. Twenty-two of 99 (22%) cases utilized a guidewire to aid in placement of PULSe. Four Clavien grade IIIb complications occurred: mucosal edema, reflex anuria, ureteral perforation, and ureteral obstruction secondary to significant clot burden. Three of the grade IIIb complications were managed endoscopically with double-J stent placement. The ureteral perforation case required percutaneous nephrostomy tube placement. Subgroup analysis of the four grade IIIb complications revealed a mean age of 62.3 years, body mass index of 26.98 kg/m(2), and pre- and postprocedural creatinine levels of 0.95 and 4.83 mg/dL, respectively. Only one of the four grade IIIb complications utilized a guidewire prior to PULSe placement. CONCLUSIONS: The incidence of Clavien grade III urologic-induced complications during PULSe placement is approximately 2% (4/188). Mandatory adoption of fluoroscopy and guidewires may be required to minimize complications of PULSe placement.

Impact of fellowship training on robotic-assisted laparoscopic partial nephrectomy: benchmarking perioperative safety and outcomes.

To provide perioperative benchmark data for surgeons entering practice from formal robotic training and performing robotic-assisted laparoscopic partial nephrectomy (RAPN). Perioperative outcomes of the first 100 RAPN from a surgeon entering into practice directly from robotic fellowship training were analyzed. Postoperative complications were categorized by Clavien-Dindo grade. Surgical "trifecta scores" and Margin, Ischemia, and Complication (MIC) scoring were utilized to assess surgical outcomes. Statistical analyses were performed using SAS (version 9.2; SAS Institute, Inc., Cary, North Carolina). Median age of the cohort was 63 years (22-81 years), and 34 (34.3%) patients were over age 65. Forty-one (41.4%) patients had a BMI > 30. Thirteen (13.1%) had RENAL 10-12 tumors, 22 of which (22.2%) were >4 cm in size. Median warm ischemia time was 17 min, and 13 patients had resection without warm ischemia. Five patients were converted to open partial nephrectomy, and 1 patient was converted to laparoscopic nephrectomy. Twenty-one patients (21.2%) experienced a complication, 6 of whom had a major (Clavien grade 3 or higher) complication with one grade 5 complication. Operating room time decreased with experience, but surgical complications and hospital stay did not change with experience. MIC score of renal cell carcinoma (RCC) patients was 74.7%, while the surgical trifecta was reached in 71.3 % of RCC patients. Surgeons may enter practice directly from formal robotic training and perform RAPN with perioperative outcomes, surgical complications, surgical trifecta scores, and MIC scoring in line with those the most experienced robotic partial nephrectomists.

Laparoscopic and robotic calyceal diverticulectomy: outcomes and modifications of technique.

OBJECTIVE: To examine the technique and outcomes of robotic and laparoscopic calyceal diverticulectomy in the management of symptomatic calyceal diverticula at a single center. SUBJECTS AND METHODS: Perioperative outcomes of six minimally invasive calyceal diverticulectomies (four laparoscopic and two robotic) between March 2011 and May 2014 were analyzed. Postoperative complications were categorized by Clavien-Dindo grade. RESULTS: The median age of the cohort was 35 years (range, 24-51 years), and mean body mass index was 24 kg/m(2). All 6 patients were female and presented with ipsilateral flank pain, and 3 of the 6 had coexisting recurrent urinary tract infections attributed to the calyceal diverticulum. Five of the 6 patients had failed prior surgical intervention with either endoscopic intervention or extracorporeal shock wave lithotripsy. Hilar clamping was performed in 2 of the 6 cases, with a mean warm ischemia time of 12 minutes (range, 10-14 minutes). Mean operative time was 162 minutes (range, 121-270 minutes), with no intraoperative complications. Mean blood loss was 150 mL (range, 50-300 mL), with no blood transfusions. There was one Clavien grade 1 complication and no major (Clavien grade 3 or higher) complications. Mean hospital stay was 2 days (range, 1-4 days). Four of the 6 patients were seen in follow-up, and all had complete resolution of flank pain and urinary tract infections, with no residual stones on imaging. CONCLUSIONS: Laparoscopic and robotic calyceal diverticulectomies for symptomatic calyceal diverticulum are safe, effective treatment options for symptomatic calyceal diverticula.

Accuracy and efficiency of determining urinary calculi composition using dual-energy computed tomography compared with Hounsfield unit measurements for practicing physicians.

OBJECTIVE: To compare speed and accuracy for determining urinary calculi composition between dual-energy computed tomography (DECT) and Hounsfield unit (HU) measurements of calculi by a set of reviewers at varying levels of training and practice. MATERIALS AND METHODS: Sixteen patients with known stone composition were randomly selected. Fourteen reviewers of varying levels of practice interpreted DECT and HU images from the selected patients to predict stone composition in 2 sessions (day 1: tutorial or flow sheet available for image interpretation and day 2: tutorial or flow sheet not available). Reviewers recorded HU values, stone color, and predicted stone composition as they were timed. Accuracy of image interpretation, determination of calculi composition, and interpretation time were compared. RESULTS: DECT accuracy: image interpretation 100% (day 1) and 94% (day 2); predicted stone composition: 100% (day 1) and 73% (day 2). Mean interpretation time was the same for both days, 21 seconds per study (range, 11-40 seconds). HU accuracy: image interpretation 97% (day 1) and 91% (day 2); predicted stone composition was 45% accurate on both days. Mean interpretation time was 53 seconds per study (range, 28-79 seconds) and 41 seconds per study (range, 19-71 seconds) on days 1 and 2, respectively. Overall accuracy of determination of stone composition and interpretation time for DECT were essentially double those of the HU images (87% vs 45% and 21 vs 47 seconds, respectively). Reviewer's experience level did not affect accuracy or speed. CONCLUSION: DECT is easier to learn, faster to interpret, and more accurate than HU in determining urinary calculi composition for physicians at various levels of training and practice.

Assessment of virtual reality robotic simulation performance by urology resident trainees.

OBJECTIVES: To examine resident performance on the Mimic dV-Trainer (MdVT; Mimic Technologies, Inc., Seattle, WA) for correlation with resident trainee level (postgraduate year [PGY]), console experience (CE), and simulator exposure in their training program to assess for internal bias with the simulator. DESIGN: Residents from programs of the Southeastern Section of the American Urologic Association participated. Each resident was scored on 4 simulator tasks (peg board, camera targeting, energy dissection [ED], and needle targeting) with 3 different outcomes (final score, economy of motion score, and time to complete exercise) measured for each task. These scores were evaluated for association with PGY, CE, and simulator exposure. SETTING: Robotic skills training laboratory. PARTICIPANTS: A total of 27 residents from 14 programs of the Southeastern Section of the American Urologic Association participated. RESULTS: Time to complete the ED exercise was significantly shorter for residents who had logged live robotic console compared with those who had not (p = 0.003). There were no other associations with live robotic console time that approached significance (all p ≥ 0.21). The only measure that was significantly associated with PGY was time to complete ED exercise (p = 0.009). No associations with previous utilization of a robotic simulator in the resident's home training program were statistically significant. CONCLUSIONS: The ED exercise on the MdVT is most associated with CE and PGY compared with other exercises. Exposure of trainees to the MdVT in training programs does not appear to alter performance scores compared with trainees who do not have the simulator.

Structure of insoluble rat sperm glyceraldehyde-3-phosphate dehydrogenase (GAPDH) via heterotetramer formation with Escherichia coli GAPDH reveals target for contraceptive design.

Sperm glyceraldehyde-3-phosphate dehydrogenase has been shown to be a successful target for a non-hormonal contraceptive approach, but the agents tested to date have had unacceptable side effects. Obtaining the structure of the sperm-specific isoform to allow rational inhibitor design has therefore been a goal for a number of years but has proved intractable because of the insoluble nature of both native and recombinant protein. We have obtained soluble recombinant sperm glyceraldehyde-3-phosphate dehydrogenase as a heterotetramer with the Escherichia coli glyceraldehyde-3-phosphate dehydrogenase in a ratio of 1:3 and have solved the structure of the heterotetramer which we believe represents a novel strategy for structure determination of an insoluble protein. A structure was also obtained where glyceraldehyde 3-phosphate binds in the P(s) pocket in the active site of the sperm enzyme subunit in the presence of NAD. Modeling and comparison of the structures of human somatic and sperm-specific glyceraldehyde-3-phosphate dehydrogenase revealed few differences at the active site and hence rebut the long presumed structural specificity of 3-chlorolactaldehyde for the sperm isoform. The contraceptive activity of alpha-chlorohydrin and its apparent specificity for the sperm isoform in vivo are likely to be due to differences in metabolism to 3-chlorolactaldehyde in spermatozoa and somatic cells. However, further detailed analysis of the sperm glyceraldehyde-3-phosphate dehydrogenase structure revealed sites in the enzyme that do show significant difference compared with published somatic glyceraldehyde-3-phosphate dehydrogenase structures that could be exploited by structure-based drug design to identify leads for novel male contraceptives.