Expert Consensus on Pediatric Urodynamics Reporting Using Modified Delphi Technique.

PURPOSE: Urodynamic testing (UDS) is an important tool in the management of pediatric lower urinary tract conditions. There have been notable efforts to standardize pediatric UDS nomenclature and technique, but no formal guidelines exist on essential elements to include in a clinical report. We sought to identify ideal structure and elements of a pediatric UDS assessment based on expert consensus. MATERIALS AND METHODS: Pediatric urologists regularly performing UDS were queried using a Delphi process. Participants were invited representing varied geographic, experience, and societal involvement. Participants underwent 3 rounds of questionnaires between November 2022 and August 2023 focusing on report organization, elements, definitions, and automated electronic health record clinical decision support. Professional billing requirements were also considered. Consensus was defined as 80% agreeing either in favor of or against a topic. Elements without consensus were discussed in subsequent rounds. RESULTS: A diverse sample of 30 providers, representing 27 institutions across 21 US states; Washington, District of Columbia; and Canada completed the study. Participants reported interpreting an average number of 5 UDS reports per week (range 1-22). The finalized consensus report identifies 93 elements that should be included in a pediatric UDS report based on applicable study conditions and findings. CONCLUSIONS: This consensus report details the key elements and structure agreed upon by an expert panel of pediatric urologists. Further standardization of documentation should aid collaboration and research for patients undergoing UDS. Based on this information, development of a standardized UDS report template using electronic health record implementation principles is underway, which will be openly available for pediatric urologists.

Peripubertal Presentation of Metastatic Testicular Mixed, Nonseminomatous Germ Cell Tumor.

Testicular tumors are relatively rare in children and those in prepubertal children tend to present with different histological types and behaviors than their postpubertal counterparts. The majority of these pre- and peripubertal testicular tumors tend to be benign and those that are malignant, tend to present at low stages, not generally requiring systemic treatment. Here we present a rare case of a peri-pubertal, mixed nonseminomatous germ cell tumor of the testes which was found to be widely metastatic at presentation, classifying as poor risk disease.

Vaginal Rhabdoid Tumor Presenting as Prenatal Lower Urinary Tract Obstruction and Vaginal Mass.

Extracranial malignant rhabdoid tumors (MRT) are very rare and aggressive tumors. They are typically associated with an extremely poor prognosis, particularly when seen in the infant and neonatal population. Here we present the case of a newborn female born with a large vaginal mass and evidence of prenatal lower urinary tract obstruction that was determined to be a MRT of vaginal origin. In this report, we will also discuss an overview of extracranial MRT tumor biology and treatment considerations.

Multifocal Paraganglioma in Teenager Presenting With Hypertension.

Pediatric hypertension represents a rare though increasingly common medical problem. When encountered, a workup to determine the etiology should be conducted. In this report, we detail an unusual case in which a teenager presenting with hypertension was found to have multifocal primary paragangliomas. We illustrate important considerations in management which include appropriate preoperative labs and imaging, collaboration with endocrinology for preoperative alpha-blockade, surgical management with close perioperative hemodynamic control, and genetic evaluation for all patients with paragangliomas.

Elimination of Postoperative Narcotics in Infant Robotic Pyeloplasty Using Caudal Anesthesia and a Non-Narcotic Pain Pathway.

Introduction: Research suggests that narcotic pain medications are dramatically overprescribed. We hypothesize that narcotics are unnecessary for postoperative pain control in most infants undergoing robotic pyeloplasty. In this series, we report our experience combining caudal blocks with a non-narcotic postoperative pathway as a means of eliminating postoperative narcotics after infant robotic pyeloplasty. Methods: We reviewed 24 consecutive patients who underwent robotic pyeloplasty by a single surgeon treated with an end-procedure caudal block followed by a non-narcotic postoperative pain pathway treated between May 2017 and May 2021. The standardized postoperative pathway consisted of an end-procedure caudal block followed by alternating intravenous acetaminophen and ketorolac. We reviewed demographics, outcomes, and unscheduled health care encounters within 30 postoperative days. Results: Sixty-three percent (15/24) of patients were male and average age was 12.1 months (range 4-34 months). Fifty-eight percent (9/15) underwent surgery on the left, and 16.7% (4/24) of patients received a single postoperative dose of narcotics in the postanesthesia care unit. No patient required narcotic prescriptions at discharge or anytime thereafter. The average length of stay was 1.13 days. There was no pain-related unscheduled visits or phone calls after discharge. Conclusions: This series shows that a non-narcotic standardized pain management strategy is a viable option for infants undergoing robotic pyeloplasty. Postprocedure caudal block is a good addition to a non-narcotic pathway. In the future, we intend to expand these findings to other pediatric urologic procedures in the hope of eliminating unnecessary narcotic use.

Prenatally Diagnosed Posterior Urethral Valves: Ethical Dilemmas of Fetal Intervention.

Although anhydramnios due to in utero renal failure has traditionally been considered lethal, in utero interventions offer the potential for pulmonary survival. As fetal interventions become more common, questions arise about how to identify and counsel eligible candidates.  In this report we describe the presentation and management of a 17-year-old pregnant female who presented from out-of-state with severe lower urinary tract obstruction (LUTO) with associated anhydramnios, focusing on the ethical questions that this case raised.

Pudendal Neuromodulation is Feasible and Effective After Pudendal Nerve Entrapment Surgery.

BACKGROUND: Patients with intractable pain in the pudendal nerve distribution may benefit from pudendal neuromodulation; however, some may have previously undergone pudendal nerve entrapment surgery (PNES), potentially altering nerve anatomy and function. AIM: We examined pudendal neuromodulation outcomes in patients with prior PNES. METHODS: Patients with a history of PNES and quadripolar, tined pudendal lead placement for urogenital pain were reviewed. Symptoms and outcomes were collected from existing medical records. OUTCOMES: Patients with pudendal neuromodulation and prior PNES were compared to patients with no prior PNES who had pudendal lead placement. RESULTS: Fifteen patients with a history of 1, 2, or 3 prior PNES (n = 13, 1, and 1, respectively) were evaluated. Most (10; 67%) were female, with bilateral pain (9; 60%), and symptoms of 5-26 years. After trialing the lead, bladder symptoms and pain were improved in 8 of 12 and 9 of 14 patients, respectively, and 80% of patients (12/15) underwent permanent generator implantation. When prior PNES patients were compared to those with no prior PNES (n = 43), gender (67% vs 77% female; P = .50) and age (median 63 vs 58 years; P = .80), were similar; however, BMI differed (mean 24 vs 29; P = .008) and a lower proportion (12/15; 80% vs 42/43; 98%; P = .049) had generator implantation. Importantly, median lead implant time (48 vs 50 minutes; P = .65) did not differ between the 2 groups. CLINICAL IMPLICATIONS: Pudendal neuromodulation has the potential to provide pain relief for a very difficult-to-treat population; furthermore, it does not appear that prior PNES surgery made lead placement significantly more challenging. STRENGTHS & LIMITATIONS: Study strengths include being a tertiary referral center for urogenital pain and having a single surgeon perform all procedures in a regimented way. Limitations include the retrospective study design, small sample size and various approaches to PN CONCLUSION: Chronic pudendal neuromodulation can be a viable option even after prior PNES. Kristen M. Meier, Patrick M. Vecellio, Kim A. Killinger, Judith A. Boura, Kenneth M. Peters. Pudendal Neuromodulation is Feasible and Effective After Pudendal Nerve Entrapment Surgery. J Sex Med 2022;19:995-1001.

Performance of a Paired-End Sequencing-Based Noninvasive Prenatal Screening Test in the Detection of Genome-Wide Fetal Chromosomal Anomalies.

BACKGROUND: Noninvasive prenatal tests (NIPTs) detect fetal chromosomal anomalies with high clinical sensitivity and specificity. We examined the performance of a paired-end sequencing-based NIPT in the detection of genome-wide fetal chromosomal anomalies including common trisomies, sex chromosomal aneuploidies (SCA), rare autosomal aneuploidies (RAAs), and partial deletions/duplications ≥7 Mb. METHODS: Frozen plasma samples from pregnant women were tested using the VeriSeq NIPT Solution v2 assay. All samples were previously tested with a laboratory-developed NIPT and had known clinical outcomes. Individuals performing the sequencing were blinded to clinical outcome data. Clinical sensitivity and specificity were determined for basic (chromosomes 21, 18, 13, X, and Y) and genome-wide screening modes. RESULTS: Of 2335 samples that underwent genome-wide analysis, 28 did not meet QC requirements, resulting in a first-pass assay failure rate of 1.2%. Basic screening analysis, excluding known mosaics, correctly classified 130/130 trisomy 21 samples (sensitivity >99.9%, 95% confidence interval [CI] 97.1%-100%), 41/41 trisomy 18 samples (sensitivity >99.9%, 95% CI 91.4%-100%), and 26/26 trisomy 13 samples (sensitivity >99.9%, 95% CI 87.1%-100%) with 6 false-positive results; specificities ≥99.90% were reported for all 3 trisomies. Concordance for SCAs ranged from 90.5%-100%. Genome-wide screening analysis including known mosaics correctly classified 27/28 RAAs and 20/27 partial deletions/duplications with a specificity of 99.80% for both anomalies, and an overall genome-wide specificity for all anomalies of 99.34%. CONCLUSIONS: The VeriSeq NIPT Solution v2 assay enables accurate identification of fetal aneuploidy, allowing detection of genome-wide fetal chromosomal anomalies with high clinical sensitivities and specificities and a low assay failure rate.Clinical Trial Notification [CTN] identification number [ID]: CT-2018-CTN-01585-1 v1, Protocol: NIPT T05 002.

Understanding Ureteral Access Sheath Use Within a Statewide Collaborative and Its Effect on Surgical and Clinical Outcomes.

Introduction: Ureteral access sheaths (UASs) are frequently used during ureteroscopy (URS), but their use is not without potential risk. We investigated patterns of UAS use and associated outcomes across practices in Michigan within a quality improvement collaborative. Methods: The Michigan Urological Surgery Improvement Collaborative (MUSIC) Reducing Operative Complications from Kidney Stones (ROCKS) initiative maintains a web-based, prospective clinical registry of patients undergoing URS for urinary stone disease (USD). We analyzed all patients undergoing primary URS for renal and ureteral stones from June 2016 to July 2018 in the ROCKS registry. We determined rates of UAS usage across practices and associated outcomes, including 30-day emergency department (ED) visits and hospitalization, as well as stone-free rates. Using multivariate logistical regression, we determined the predictors of UAS use as well as outcomes, including stone-free rates, ED visits, and hospitalizations, associated with UAS use. Results: Of the 5316 URS procedures identified, UASs were used in 1969 (37.7%) cases. Stones were significantly larger and more likely to be located in the kidney in cases with UAS use. UAS use during URS varied greatly across practices (1.9%-96%, p < 0.05). After adjusting for clinical and surgical risk factors, UAS use significantly increased the odds of postoperative ED visits (odds ratio [OR] = 1.50, 95% confidence interval [CI] 1.17-1.93, p < 0.05) and hospitalization (OR = 1.77, 95% CI 1.22-2.56, p < 0.05) as well as decreased the odds of being stone free (OR = 0.75, 95% CI 0.57-0.99, p < 0.05). Conclusions: In the current study, UAS use during URS for USD was not associated with an increased likelihood of being stone free; moreover, it increased the odds of a postoperative ED visit and or hospitalization. Our findings demonstrate that UAS use is not without risk and should be employed judiciously.

Development and Analytical Validation of a DNA Dual-Strand Approach for the US Food and Drug Administration-Approved Next-Generation Sequencing-Based Praxis Extended RAS Panel for Metastatic Colorectal Cancer Samples.

A next-generation sequencing method was developed that can distinguish single-stranded modifications from low-frequency somatic mutations present on both strands of DNA in formalin-fixed paraffin-embedded colorectal cancer samples. We applied this method for analytical validation of the Praxis Extended RAS Panel, a US Food and Drug Administration-approved companion diagnostic for panitumumab, on the Illumina MiSeqDx platform. With the use of the TruSeq amplicon workflow, both strands of DNA from the starting material were interrogated independently. Mutations were reported only if found on both strands; artifacts usually present on only one strand would not be reported. A total of 56 mutations were targeted within the KRAS and NRAS genes. A minimum read depth of 1800× per amplicon is required per sample but averaged >30,000× at maximum multiplexing levels. Analytical validation studies were performed to determine the simultaneous detection of mutations on both strands, reproducibility, assay detection level, precision of the assay across various factors, and the impact of interfering substances. In conclusion, this assay can clearly distinguish single-stranded artifacts from low-frequency mutations. Furthermore, the assay is accurate, precise, and reproducible, can achieve consistent detection of a mutation at 5% mutation frequency, exhibits minimal impact from tested interfering substances, and can simultaneously detect 56 mutations in a single run using 10 samples plus controls.

Genetic lineage tracing of targeted cell populations during enthesis healing.

Rotator cuff supraspinatus tendon injuries are clinically challenging due to the high rates of failure after surgical repair. One key limitation to functional healing is the failure to regenerate the enthesis transition between tendon and bone, which heals by disorganized scar formation. Using two models of supraspinatus tendon injury in mouse (partial tear and full detachment/repair), the purpose of the study was to determine functional gait outcomes and identify the origin of the cells that mediate healing. Consistent with previous reports, enthesis injuries did not regenerate; partial tear resulted in a localized scar defect adjacent to intact enthesis, while full detachment with repair resulted in full disruption of enthesis alignment and massive scar formation between tendon and enthesis fibrocartilage. Although gait after partial tear injury was largely normal, gait was permanently impaired after full detachment/repair. Genetic lineage tracing of intrinsic tendon and cartilage/fibrocartilage cells (ScxCreERT2 and Sox9CreERT2 , respectively), myofibroblasts (αSMACreERT2 ), and Wnt-responsive stem cells (Axin2CreERT2 ) failed to identify scar-forming cells in partial tear injury. Unmineralized enthesis fibrocartilage was strongly labeled by Sox9CreERT2 while Axin2CrERT2 labeled a subset of tendon cells away from the skeletal insertion site. In contrast to the partial tear model, Axin2CreERT2 labeling showed considerable contribution of Axin2lin cells to the scar after full detachment/repair. Clinical Significance: Clinically relevant models of rotator cuff tendon injuries in mouse enable the use of genetic tools; lineage tracing suggests that distinct mechanisms of healing are activated with full detachment/repair injuries versus partial tear. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3275-3284, 2018.

Clinical validation of the next-generation sequencing-based Extended RAS Panel assay using metastatic colorectal cancer patient samples from the phase 3 PRIME study.

PURPOSE: To validate a next-generation sequencing (NGS)-based companion diagnostic using the MiSeqDx® sequencing instrument to simultaneously detect 56 RAS mutations in DNA extracted from formalin-fixed paraffin-embedded metastatic colorectal cancer (mCRC) tumor samples from the PRIME study. The test's ability to identify patients with mCRC likely to benefit from panitumumab treatment was assessed. METHODS: Samples from PRIME, which compared first-line panitumumab + FOLFOX4 with FOLFOX4, were processed according to predefined criteria using a multiplex assay that included input DNA qualification, library preparation, sequencing, and the bioinformatics reporting pipeline. NGS mutational analysis of KRAS and NRAS exons 2, 3, and 4 was performed and compared with Sanger sequencing. RESULTS: In 441 samples, positive percent agreement of the Extended RAS Panel with Sanger sequencing was 98.7% and negative percent agreement was 97.6%. For clinical validation (n = 528), progression-free survival (PFS) and overall survival (OS) were compared between patients with RAS mutations (RAS Positive) and those without (RAS Negative). Panitumumab + FOLFOX4 improved PFS in RAS Negative patients (P = 0.02). Quantitative interaction testing indicated the treatment effect (measured by the hazard ratio of panitumumab + FOLFOX4 versus FOLFOX4) differed for RAS Negative versus RAS Positive for PFS (P = 0.0038) and OS (P = 0.0323). CONCLUSIONS: NGS allows for broad, rapid, highly specific analyses of genomic regions. These results support use of the Extended RAS Panel as a companion diagnostic for selecting patients for panitumumab, and utilization is consistent with recent clinical guidelines regarding mCRC RAS testing. Overall, approximately 13% more patients were detected with the Extended RAS Panel versus KRAS exon 2 alone. CLINICAL TRIAL REGISTRY IDENTIFIER: NCT00364013 (ClinicalTrials.gov).

Pediatric elbow arthroscopy: indications and safety.

BACKGROUND: Elbow arthroscopy is a minimally invasive means by which to treat a variety of acute and chronic elbow conditions. Although the safety and efficacy is well documented in the adult population, comparatively little information is available about the role of elbow arthroscopy in the pediatric population. This study reports the indications for and safety of elbow arthroscopy in a series of pediatric patients. METHODS: A retrospective review was performed from 2001 to 2015 of a surgical database at a single institution. All elbow arthroscopies performed in patients aged 18 years and younger were reviewed. Indications for surgery, perioperative and postoperative complications, further surgical intervention, and descriptive demographic information were recorded. RESULTS: We identified 64 elbow arthroscopic procedures in 59 patients. The average age at the time of surgery was 11.8 years. Indications for the arthroscopic surgery included contracture release (45.3%), closed reduction and fixation for fracture (20.3%), treatment of osteochondritis dissecans (20.3%), diagnostic arthroscopy (7.8%), and débridement (6.3%). The overall complication rate was 17.2%, with a major and minor complication rate of 6.3% and 10.9%, respectively. CONCLUSION: Elbow arthroscopy has applications in the pediatric population with an acceptable safety profile. The techniques and indications continue to evolve.

Day of Surgery and Surgical Start Time Affect Hospital Length of Stay After Total Hip Arthroplasty.

BACKGROUND: The United States spends $12 billion each year on ∼332,000 total hip arthroplasty (THA) procedures with the postoperative period accounting for ∼40% of costs. The purpose of this study was to evaluate the effect of surgical scheduling (day of week and start time) on clinical outcomes, hospital length of stay (LOS), and rate of nonhome discharge in THA patients. METHODS: Analysis of perioperative variables was performed for patients who underwent THA at an urban tertiary care teaching hospital from 2009 to 2014. RESULTS: A total of 580 THA patients were included for analysis. LOS was higher for the Thursday/Friday cohort compared to Monday/Tuesday (3.7 vs 3.4 days; P = .03). Patients who had a surgical start time after 2 PM had longer LOS compared to patients operated on before 2 PM (3.9 vs 3.5 days; P = .03). After controlling for patient comorbidities and THA surgical approach (direct anterior vs posterior), Thursday/Friday THAs were associated with a 3.27 times risk of extended LOS (>75th percentile LOS) compared to Monday/Tuesday THAs (P < .001). Additionally, case start before 2 PM was protective and associated with a 0.46 times odds of extended LOS (P = .01). LOS reduction opportunity for changing surgical start time to before 2 PM was 0.9 days for high-risk patients (American Society of Anesthesiology class 3/4 and/or liver disease) and 0.2 days for low-risk patients (American Society of Anesthesiology class 1/2). CONCLUSION: Patients who underwent THA Thursday/Friday or had start times after 2 PM had significantly extended hospital LOS. Preoperative risk modification along with adjustments to surgical scheduling and/or perioperative staffing may reduce LOS and thus hospital expenditures for THA procedures.

Female bladder outlet obstruction: an update on diagnosis and management.

PURPOSE OF REVIEW: The diagnosis and evaluation of bladder outlet obstruction (BOO) in women remains a challenging topic. The goal of this study is to review recent literature and summarize the diagnosis and management of BOO with special focus on recent progress. RECENT FINDINGS: In recent years, numerous advances in the area of female BOO have taken place including a movement towards unified diagnostic criteria, summary of functional and anatomic causes, and exploration of potential diagnostic options. SUMMARY: This review discusses the known diagnosis and management of female bladder outlet obstruction, yet highlights specific functional causes, new criteria available for diagnosis, and long-term results of treatment options.

Brachialis syndrome: a rare consequence of patient positioning causing postoperative median neuropathy.

BACKGROUND: Poor positioning of patients can result in devastating permanent neurologic deficits. We describe a previously unreported cause of median nerve compression that we have termed the brachialis syndrome, associated with patient positioning that results in permanent median nerve damage. METHODS: We identified this condition affecting 6 median nerves. All patients underwent surgical decompression of the proximal median nerve at the level of the antecubital fossa. RESULTS: Five patients presented with symptoms of median nerve compression; 6 affected median nerves manifested brachialis syndrome after a lengthy index surgery. Every patient had a similar presentation characterized by a mixed sensory and motor deficit. Average time to symptom presentation postoperatively was 1 hour. Two patients had delayed time to decompression, one of 25 days and one of 92 days. In the additional patients, the average time to decompression was 19.7 hours. At median nerve decompression, the brachialis was found to have varying degrees of muscle necrosis. In the patients whose decompression was delayed, there was only partial neurologic recovery at follow-up to 1 year. In the patients expeditiously decompressed, full neurologic recovery occurred in 1 to 14 days. CONCLUSIONS: This is the first description of the brachialis syndrome. During surgery, arms were placed into full extension, compressing the brachialis against the trochlea. The brachialis reliably developed necrosis, resulting in swelling, compressing the median nerve against the lacertus fibrosus. Two patients with delayed decompression had poor neurologic outcomes. This supports modification of patient positioning, postoperative vigilance, and timely surgical management of brachialis syndrome.

The effects of short-term vitamin D supplementation on glucose metabolism in dialysis patients: a systematic review and meta-analysis.

PURPOSE: We tested whether short-term vitamin D supplementation improves insulin resistance in patients with kidney disease, a condition with little intrinsic vitamin D activity. METHODS: PubMed, EMBASE and CENTRAL were searched for relevant observational studies and randomized clinical trials (RCTs). Random-effects models were employed for meta-analysis, and effect sizes were summarized as standardized mean difference (SMD) with 95% confidence intervals. Separate analyses were done for RCTs and non-randomized intervention studies (NRIS). RESULTS: Seventeen studies (5 RCTs and 12 NRIS) were included. The meta-analysis population (n = 131) was mostly middle aged (40-50 years), male and non-diabetic, and on hemodialysis. The duration (4-12 weeks) and type of supplementation varied between studies. Among RCTs, compared to placebo, vitamin D supplementation was associated with significant decrease in fasting glucose [SMD -1.13, (-2.11 to -0.11)] and PTH levels [SMD -1.50, (-2.95 to -0.04)] but no difference in fasting insulin levels [SMD 1.32, (-0.15 to 2.79)]. Among NRIS, there was only a significant decrease in PTH levels [SMD -1.68, (-2.55 to -0.82)] between pre- and post-vitamin D treatment levels. CONCLUSIONS: Short-term (4-12 weeks) supplementation with vitamin D is associated with lower fasting glucose levels in ESRD with no change in fasting insulin levels. However, the findings from this study are limited by the studies that were used in the meta-analysis, which were mostly small, used multiple different vitamin D compounds and dosing regimens, and had large heterogeneity, and funnel plots showed that there was a dearth of studies with null or negative finding. Therefore, larger RCTs need to be performed to answer this important clinical question.