Deferring gonadectomy in patients with turner syndrome with a genetic Y component is not a safe practice.

INTRODUCTION: Patients with Turner syndrome who harbor Y chromosome material are known to be at increased risk of developing germ cell neoplasms. The optimal timing to perform gonadectomy to reduce the risk of cancer development in these patients is not well defined. We present outcomes of Turner with a Y component (TSY) patients who underwent gonadectomy at our institution. HYPOTHESIS/OBJECTIVE: We hypothesized that tumors could occur in a significant portion of TSY patients at any age and gonadectomy can be safely performed at diagnosis rather than deferred. STUDY DESIGN: We performed an IRB-approved retrospective single center study in which we queried our institutions electronic health record to identify all patients with TSY who underwent gonadectomy at our institution from 2012 to 2021. RESULTS: In our series of 18 consecutive TSY patients, a tumor was identified in 6 patients (33.3%): 4 (22.2%) with dysgerminoma (DG) [Fig. 1] and 2 (11.1%) with gonadoblastoma (GB). DISCUSSION: Our cohort of 18 consecutive TSY who underwent gonadectomy over a 9-year period is the largest published single site cohort to date. Additionally, our patient who was found to have GB at 40 days is to our knowledge the youngest TSY patient to be diagnosed with GB in the literature. This patient's remarkably early incidence of tumor occurrence illustrates the urgency of protective gonadectomy. Given the high incidence of tumor formation in this population and the minimal morbidity associated with gonadectomy, we do not recommend delaying gonadectomy in this population for any reason. Our study is vulnerable to selection bias and confounding innate to any retrospective study. There was variation with respect to the frequency and timing of pre-operative imaging as a strict preoperative imaging protocol with sequential studies was not in place at our institution. Additionally, we do not have a comparison cohort of patients who are being followed without operative intervention as all TSY patients at our institution have undergone gonadectomy. CONCLUSION: TSY patients cannot be safely observed for tumor formation based on clinical factors such as imaging or age. Gonadectomy is safe with a low complication rate and without tumor recurrence during three-year follow-up. We continue to recommend bilateral gonadectomy in this patient population at the time of diagnosis.

Single institution experience with telemedicine for pediatric urology outpatient visits: Adapting to COVID-19 restrictions, patient satisfaction, and future utilization.

INTRODUCTION: Widespread utilization of telemedicine in our practice to date has been limited to the evaluation of certain post-surgical patients. The COVID-19 pandemic acutely stressed our established system and required us to enhance our utilization of telemedicine. We hypothesized that expansion of telemedicine to new and follow up patient visits for pediatric urology could be done effectively in a way that satisfied patient and parental expectations. MATERIALS AND METHODS: Using a pre-COVID-19 established telemedicine program based in our electronic medical record (EMR), patients and providers transitioned to primarily virtual visits when clinically appropriate. Guidelines were formulated to direct patient scheduling, provider and staff education was provided, including a process map designed for multiple providers to complete video visits (VV), and the EMR was redesigned to incorporate telehealth terminology. The number of VV per provider was recorded using the electronic medical record, and patient reported outcomes (PRO) were measured using a standardized questionnaire. RESULTS: A total of 631 VV met inclusion criteria during the period of May 2018-April 2020. This included 334 follow up, 172 new, and 125 postoperative visits. The median age of patients at time of visit was 7 years (IQR 2-12 years), median visit time was 20 min (IQR 15-30 min), and the median travel distance saved by performing a VV was 12.2 miles (IQR 6.3-26.8 miles). Diagnoses were varied and included the entire breadth of a standard pediatric urology practice. The PRO questionnaire was completed for 325 of those patient visits. Families reported a high overall satisfaction with the video visits (median score of 10 out of 10) and felt that the visit met their child's medical needs. 90% stated that they would strongly recommend a telehealth visit to other families. Patients and parents reported benefits of VV including decreased travel costs and less time taken off from work and school. CONCLUSION: The EMR enabled nimble redirection of clinical care in the setting of a global pandemic. The enhanced use of telemedicine has proved to be an alternative method to provide care for pediatric urology patients. Families indicate a high degree of satisfaction with this technology in addition to significant time and cost savings. Telemedicine should remain a key aspect of medical care and expanded from post-operative visits to new patient and follow up visits, even as we return to our normal practices as the pandemic restrictions soften.

Reducing post-operative opioids in children undergoing outpatient urologic surgery: A quality improvement initiative.

INTRODUCTION: Opioid prescriptions have been implicated as one of the proximate causes of the national opioid epidemic. Children and adolescents and their families are at risk for increased opioid exposure through prescriptions after surgery. In pediatric urologic surgery, indications for postoperative opioids can vary widely and a focus on opioid stewardship is important to reduce potential harms. OBJECTIVE: To measure the efficacy of a quality improvement initiative aimed to reduce post-operative opioids for pain management in a large pediatric surgical cohort. STUDY DESIGN: Patients undergoing ambulatory pediatric urologic surgery at a tertiary children's hospital between July 2016 to June 2019 were analyzed. Structured physician peer-to-peer comparisons, electronic health record redesign and a standardized pain management protocol were implemented. Rate of opioid prescriptions per month, utilization of non-opioid analgesia, unplanned encounters in the emergency department and/or office during implementation were aggregated. Opioid doses and prescribed opioid days before and after protocol implementation were analyzed. A subcohort, from October-December 2018 was administered a patient-reported outcome questionnaire focused on pain management and return to baseline activity. RESULTS: A total of 6684 consecutive outpatient urologic cases were included (median age = 3.3 years old (IQR 0.9-9.2) and 92.3% male). Comparing 6 months pre-intervention and the post-intervention latest 6 month intervals, opioid prescription rate decreased from 43.9% to 2.3% (p < 0.001). Additionally, non-opioid analgesia with ketorolac increased from 30.7% to 50.6% (p < 0.001). Concurrently, no differences in the rate of office visits within 5 days, overall ED visits, ED visits for pain or for bleeding within 30 days after implementation were identified. Between October to December 2018, 373 cases were performed and a Patient-Reported Outcome (PRO) questionnaire was completed for 128 of those patients (34%). Families reported a low patient pain score of 3.7 (SD 2.4) and a rapid postoperative recovery time of a median 2 (IQR 1-4) days to full resumption of pre-operative level of activity. High satisfaction with opioid reduction in post-operative pain management was reported (median score of 10 (IQR 8-10)). CONCLUSION: Opioid prescriptions and utilization may be minimized without increasing unplanned encounters or adversely affecting quality of life. The QI framework utilized in this process can be implemented to reduce opioid exposure in other surgical patient populations.

A stochastic epigenetic switch controls the dynamics of T-cell lineage commitment.

Cell fate decisions occur through the switch-like, irreversible activation of fate-specifying genes. These activation events are often assumed to be tightly coupled to changes in upstream transcription factors, but could also be constrained by cis-epigenetic mechanisms at individual gene loci. Here, we studied the activation of Bcl11b, which controls T-cell fate commitment. To disentangle cis and trans effects, we generated mice where two Bcl11b copies are tagged with distinguishable fluorescent proteins. Quantitative live microscopy of progenitors from these mice revealed that Bcl11b turned on after a stochastic delay averaging multiple days, which varied not only between cells but also between Bcl11b alleles within the same cell. Genetic perturbations, together with mathematical modeling, showed that a distal enhancer controls the rate of epigenetic activation, while a parallel Notch-dependent trans-acting step stimulates expression from activated loci. These results show that developmental fate transitions can be controlled by stochastic cis-acting events on individual loci.

Asynchronous combinatorial action of four regulatory factors activates Bcl11b for T cell commitment.

During T cell development, multipotent progenitors relinquish competence for other fates and commit to the T cell lineage by turning on Bcl11b, which encodes a transcription factor. To clarify lineage commitment mechanisms, we followed developing T cells at the single-cell level using Bcl11b knock-in fluorescent reporter mice. Notch signaling and Notch-activated transcription factors collaborate to activate Bcl11b expression irrespectively of Notch-dependent proliferation. These inputs work via three distinct, asynchronous mechanisms: an early locus 'poising' function dependent on TCF-1 and GATA-3, a stochastic-permissivity function dependent on Notch signaling, and a separate amplitude-control function dependent on Runx1, a factor already present in multipotent progenitors. Despite their necessity for Bcl11b expression, these inputs act in a stage-specific manner, providing a multitiered mechanism for developmental gene regulation.