Current and emerging strategies to curb antibiotic-resistant urinary tract infections.

Rising rates of antibiotic resistance in uropathogenic bacteria compromise patient outcomes and prolong hospital stays. Consequently, new strategies are needed to prevent and control the spread of antibiotic resistance in uropathogenic bacteria. Over the past two decades, sizeable clinical efforts and research advances have changed urinary tract infection (UTI) treatment and prevention strategies to conserve antibiotic use. The emergence of antimicrobial stewardship, policies from national societies, and the development of new antimicrobials have shaped modern UTI practices. Future UTI management practices could be driven by the evolution of antimicrobial stewardship, improved and readily available diagnostics, and an improved understanding of how the microbiome affects UTI. Forthcoming UTI treatment and prevention strategies could employ novel bactericidal compounds, combinations of new and classic antimicrobials that enhance bacterial killing, medications that prevent bacterial attachment to uroepithelial cells, repurposing drugs, and vaccines to curtail the rising rates of antibiotic resistance in uropathogenic bacteria and improve outcomes in people with UTI.

Murine Ribonuclease 6 Limits Bacterial Dissemination During Experimental Urinary Tract Infection.

INTRODUCTION: The Ribonuclease (RNase) A superfamily encodes cationic antimicrobial proteins with potent microbicidal activity toward uropathogenic bacteria. Ribonuclease 6 (RNase6) is an evolutionarily conserved, leukocyte-derived antimicrobial peptide with potent microbicidal activity toward uropathogenic Escherichia coli (UPEC), the most common cause of bacterial urinary tract infections (UTI). In this study, we generated Rnase6 deficient mice to investigate the hypothesis that endogenous RNase 6 limits host susceptibility to UTI. METHODS: We generated a Rnase6EGFP knock-in allele to identify cellular sources of Rnase6 and determine the consequences of homozygous Rnase6 deletion on antimicrobial activity and UTI susceptibility. RESULTS: We identified monocytes and macrophages as the primary cellular sources of Rnase6 in bladders and kidneys of Rnase6EGFP/+ mice. Rnase6 deficiency (i.e., Rnase6EGFP/EGFP) resulted in increased upper urinary tract UPEC burden during experimental UTI, compared to Rnase6+/+ controls. UPEC displayed increased intracellular survival in Rnase6 deficient macrophages. CONCLUSION: Our findings establish that RNase6 prevents pyelonephritis by promoting intracellular UPEC killing in monocytes and macrophages and reinforce the overarching contributions of endogenous antimicrobial RNase A proteins to host UTI defense.

Surgeon, and Institution Characteristics Associated Surgical Preferences in the Pediatric KIDney Stone Care Improvement Network.

OBJECTIVE: To reveal barriers and opportunities to implement evidence for the management of pediatric kidney stone disease, we determined surgeon and institutional factors associated with preferences for the type of surgical intervention for kidney and ureteral stones. METHODS: We conducted a cross-sectional study of urologists participating in the Pediatric KIDney Stone Care Improvement Network (PKIDS) trial. Questionnaires ascertained strengths of urologists' preferences for types of surgery as well as characteristics of participating urologists and institutions. The outcome was the strength of preferences for ureteroscopy, shockwave lithotripsy, and percutaneous nephrolithotomy for four scenarios for which two alternative procedures are recommended by the AUA guidelines: (1) 2 cm kidney stone, (2) 9 mm proximal ureteral stone, (3) 1.5 cm lower pole kidney stone, (4) 1 cm nonlower pole kidney stone. Principal component analysis was performed to identify unique clusters of factors that explain surgical preferences. RESULTS: One hundred forty-eight urologists at 29 sites completed surveys. Stated preferences were highly skewed except for the choice between ureteroscopy and percutaneous nephrolithotomy for a 1.5 cm kidney stone. Shockwave lithotripsy ownership and local practice patterns most frequently associated with the strength of surgeons' preferences for the type of surgery. Principal component analysis revealed that three clusters of stone, patient, and heterogenous characteristics explained 30% of the variance in preferences. CONCLUSION: There is wide variation in the strengths of preferences for surgical interventions supported by current guidelines that are partially explained by surgeon and institutional characteristics. These results reveal opportunities to develop strategies for guidelines that consider real-world drivers of care.

Elevating pediatric urology care: The crucial role of nursing research in quality improvement.

This educational article highlights the critical role of pediatric urology nursing research in improving the care of children with urological conditions. It discusses the multifaceted nature of pediatric urology nursing, addresses challenges such as limited nurse scientists and resource constraints, and highlights the need to overcome barriers to increase research involvement. The authors emphasize the importance of prioritizing research areas, the promotion of collaboration, and the provision of adequate funding and academic time for pediatric nurses to contribute to evidence-based practice, to improve patient outcomes. Furthermore, it highlights the importance of research in advancing nursing practice, shaping protocols, and advocating for the rights and needs of children with urological conditions and their families.

Concentration of novel urinary tract infection biomarkers in neonates.

Urinary tract infections (UTIs) are a common comorbidity in hospitalized neonates. The current UTI diagnostics have several limitations including invasive collection of urinary samples to ensure sterility, risk of contamination and lack of consensus definitions of UTI based on urine culture. Antimicrobial peptides (AMPs) have been recently utilized as novel biomarkers that can efficiently and accurately diagnose pediatric UTI. However, the concentration of AMPs in neonatal urine is not well-defined. Urine from neonates admitted to a single level IV neonatal intensive care unit was obtained to determine baseline concentration of two AMPs, Ribonuclease 7 (RNase 7) and Beta Defensin-1 (BD-1) and to define the relationship between AMP concentration and gestational age (GA). AMP levels were normalized to urine creatinine. RNase 7 and BD-1 were expressed in neonatal urine (n = 66) regardless of GA and as early as 22 weeks gestation. Urinary concentrations of both AMPs decreased as GA and birthweight increased. The overall median urinary RNase 7/UCr and BD-1/UCr values were 271 ng/mg, and 116 ng/mg, respectively. Median urinary concentrations of RNase 7/UCr for infants born at < 27, 27-32, 33-35 and ≥ 36 weeks were 569, 308, 254, and 124 ng/mg respectively. Similarly, the concentrations of BD-1/UCr at these GA were 166, 115, 108, and 14 ng/mg, respectively. Baseline neonatal urinary concentration of two AMPs (RNase 7 and BD-1) and the variation by GA were identified. This is an essential first step toward the potential utilization of AMPs in improving neonatal UTI diagnostics.

Distinguishing characteristics of pediatric patients with primary hyperoxaluria type 1 in PEDSnet.

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inborn error of metabolism that causes oxalate deposition, leading to recurrent calcium oxalate kidney stones, chronic kidney disease and systemic oxalosis, which produces a broad range of serious life-threatening complications. Patients with PH1 have delayed diagnosis due to the rarity of the disease and the overlap with early-onset kidney stone disease not due to primary hyperoxaluria. OBJECTIVE: The objective of this study was to determine the clinical features of individuals <21 years of age with PH1 that precede its diagnosis. We hypothesized that a parsimonious set of features could be identified that differentiate patients with PH1 from patients with non-primary hyperoxaluria-associated causes of early-onset kidney stone disease. STUDY DESIGN: We determined the association between clinical characteristics and PH1 diagnosis in a case-control study conducted between 2009 and 2021 in PEDSnet, a clinical research network of eight US pediatric health systems. Each patient with genetically confirmed PH1 was matched by sex and PEDSnet institution to up to 4 control patients with kidney stones without PH of any type. We obtained patient characteristics and diagnostic test results occurring before to less than 6 months after study entrance from a centralized database query and from manual chart review. Differences were examined using standardized differences and multivariable regression. RESULTS: The study sample included 37 patients with PH1 and 147 controls. Patients with PH1 were younger at diagnosis (median age of 3 vs 13.5 years); 75 % of children with PH1 were less than 8 years-old. Patients with PH1 were more likely to have combinations of nephrocalcinosis on ultrasound or CT (43 % vs 3 %), lower eGFR at diagnosis (median = 52 mL/min/1.73 m2 vs 114 mL/min/1.73 m2), and have normal mobility. Patients with PH1 had higher proportion of calcium oxalate monohydrate kidney stones than controls (median = 100 % vs 10 %). There were no differences in diagnosis of failure to thrive, stone size, or echocardiography results. CONCLUSIONS: Children with PH1 are characterized by presentation before adolescence, nephrocalcinosis, decreased eGFR at diagnosis, and calcium oxalate monohydrate stone composition. If externally validated, these characteristics could facilitate earlier diagnosis and treatment of children with PH1.

Robotic retroperitoneal lymph node dissection for paratesticular rhabdomyosarcoma in adolescents: a case series.

Robotic assisted (RA) retroperitoneal lymph node dissection (RPLND) has grown in popularity as it offers decreased morbidity and faster recovery compared to the open technique. Proponents of open surgery raised concerns about the oncological fidelity of the RA approach for testicular tumors where complete resection is needed. In boys > 10 years with paratesticular rhabdomyosarcoma (RMS), RPLND is indicated for staging purposes only. In this population, the RA technique should provide its benefits without concerns for oncological compromise. We present an analysis of RA-RPLND for boys with paratesticular RMS. We queried our institution's prospectively collected database of pediatric robotic cases for patients undergoing RA-RPLND post-radical orchiectomy for paratesticular mass, confirmed by pathology as RMS. Demographic, surgical, follow-up, and oncological outcomes were evaluated between 2017 and 2023. Five patients underwent RA-RPLND for paratesticular RMS. The median age was 16.1 years (15-17), with median OR time of 456 min (357-508). No conversions to open occurred. Inpatient median total opioid use was 1.8 (0.4-2.7) morphine equivalent/kg. The median lymph node yield was 27 (8-44) and post-op length of stay was 3 days (2-5). The median time to initiating adjuvant chemotherapy was 10.5 days (7-13). One patient had complications: pneumothorax attributed to central line placement and chyle leak that resolved in 1 week with dietary restriction. Our series demonstrates the feasibility, safety, and efficacy of the RA approach for RPLND in pediatric patients with paratesticular RMS. This is the most extensive case series currently in the literature and the only one exclusively done for paratesticular RMS.

Human Ribonuclease 6 Has a Protective Role during Experimental Urinary Tract Infection.

Mounting evidence suggests that antimicrobial peptides and proteins (AMPs) belonging to the RNase A superfamily have a critical role in defending the bladder and kidney from bacterial infection. RNase 6 has been identified as a potent, leukocyte-derived AMP, but its impact on urinary tract infection (UTI) in vivo has not been demonstrated. To test the functional role of human RNase 6, we generated RNASE6 transgenic mice and studied their susceptibility to experimental UTI. In addition, we generated bone marrow-derived macrophages to study the impact of RNase 6 on antimicrobial activity within a cellular context. When subjected to experimental UTI, RNASE6 transgenic mice developed reduced uropathogenic Escherichia coli (UPEC) burden, mucosal injury, and inflammation compared to non-transgenic controls. Monocytes and macrophages were the predominant cellular sources of RNase 6 during UTI, and RNASE6 transgenic macrophages were more proficient at intracellular UPEC killing than non-transgenic controls. Altogether, our findings indicate a protective role for human RNase 6 during experimental UTI.

Marketing yourself in social media as a global health organization: lessons to be learned.

PURPOSE: To evaluate whether X, formerly known as Twitter, is being used effectively to advance the goals of International Volunteers in Urology (IVUmed). How is X activity associated with end-user engagement? METHODS: Monthly analytics of the X account @IVUmed were reviewed between September 2014 and November 2022 using https://analytics.twitter.com/ . Outcomes included tweets, mentions, impressions, engagements, interactions, followers, and profile visits. Statistical analysis using Mann-Whitney U test and Spearman's rank-order correlation was performed. Top tweet content between December 2020 and November 2022 was also analyzed and assigned one of seven different categories: research, workshops, mission statement, educational materials, fundraising, individual spotlight, and other. RESULTS: Of @IVUmed's 1668 followers, 1334 (80.0%) were individuals. One thousand one hundred twenty-six (84.4%) individuals listed their locations with the majority (79.8%) residing in high-income countries. Tweet impressions have increased over time; they were significantly higher (p < 0.01) on average after the onset of COVID-19 in March 2020. From December 2020 to November 2022, new followers were positively correlated with tweet impressions (p < 0.01), total mentions (p < 0.01), and profile visits (p < 0.01). Profile visits were positively correlated with total tweets (p < 0.01). The content categories for monthly top tweets that proportionally garnered the most engagements were workshops (50%) and individual spotlight (29%), despite not being the most tweeted about content categories. CONCLUSION: Non-profit organizations wishing to increase their web-based outreach can benefit from increased primary X activity. While not evaluated in this study, it may also improve fundraising capabilities. Nevertheless, periodic review of account activity is important to ensure engagement of the targeted audience.

Outcomes after dextranomer/hyaluronic acid bladder neck injection in patients with urethral incontinence following bladder neck repair.

INTRODUCTION: Many patients who undergo surgery for bladder neck (BN) incompetence may still experience incontinence postoperatively. Dextranomer/hyaluronic acid (Dx/HA) is widely used for endoscopic treatment of vesicoureteral reflux in children; however, few studies have reported its use in treating incontinence after BN surgery. OBJECTIVE: The aim of this study was to evaluate outcomes after Dx/HA bladder neck injection in patients with persistent outlet incompetency following BN Repair. STUDY DESIGN: We retrospectively reviewed patients at a single pediatric tertiary care center with history of prior bladder neck surgery and reported persistent incontinence who then underwent endoscopic bladder neck Dx/HA injection from 2013 to 2018 and had subsequent follow-up post-injection. We described primary outcomes of reported incontinence as "wet" (leakage similar to before injection), "improved" (wet but leakage improved), and "dry" (no leakage). Our secondary outcome was need for a secondary procedure after Dx/HA injection, including Dx/HA injection or bladder neck closure (BNC). RESULTS: At first follow-up (median 2.3 months post-op), 7/19 were wet, 6/19 were improved, and 6/19 were dry. At last follow-up (median of 34.7 months), only three patients (16%) were dry. Only one patient who received a single surgery for Dx/HA injection was "dry", though nearly 2/3rds (12) were initially "improved" in their continence. Overall, seven patients had another intervention or surgery after first injection. Five patients had multiple Dx/HA injections after first procedure, which resulted in dryness by last assessment in two of these. Four patients (21%) in the overall cohort required subsequent BNC. DISCUSSION: Longer-term follow-up in our study demonstrated that only one patient who received a single procedure of Dx/HA injection remained dry. Several studies had follow up for greater than 1 year after initial bladder neck Dx/HA injection; rates of dryness after a single surgery for injection were variable and reported between 20 and 40% over follow-up times ranging from 1.5 to 7 years (Alova et al., 2012; DaJusta et al., 2013; Lottmann et al., 2006a; Lottmann et al., 2006b; Kitchens et al., 2007). Our st udy does have inherent limitations. This study was performed at a single institution in a retrospective manner, with a single surgeon reviewing the medical record to determine operative techniques and continence outcomes. The patient population is small, although relatively comparable to other previously reported studies. Outcomes were based on documentation of patient reports and are therefore lacking in objectivity. CONCLUSION: In patients with prior unsuccessful BN repair, long-lasting dryness after single Dx/HA BN injection is unlikely, although one-third may demonstrate relatively durable improvement in incontinence.

A Case of Multicystic Dysplastic Kidney Presenting as a Single Midline Pelvic Cyst.

We present an unusual case of a female neonate presenting with a single midline pelvic cyst. Prenatal imaging was suggestive of multicystic dysplastic kidney (MCDK), but postnatal imaging was atypical for this diagnosis given the location and singular cyst noted. The patient ultimately underwent surgical exploration and was diagnosed with an ectopic MCDK. Ectopic MCDK should be considered in the differential diagnosis of unilocular cystic pelvic lesions identified in the perinatal period.

The real world experience of pediatric primary hyperoxaluria patients in the PEDSnet clinical research network.

The rarity of primary hyperoxaluria (PH) challenges our understanding of the disease. The purpose of our study was to describe the course of clinical care in a United States cohort of PH pediatric patients, highlighting health service utilization. We performed a retrospective cohort study of PH patients < 18 years old in the PEDSnet clinical research network from 2009 to 2021. Outcomes queried included diagnostic imaging and testing related to known organ involvement of PH, surgical and medical interventions specific to PH-related renal disease, and select PH-related hospital service utilization. Outcomes were evaluated relative to cohort entrance date (CED), defined as date of first PH-related diagnostic code. Thirty-three patients were identified: 23 with PH type 1; 4 with PH type 2; 6 with PH type 3. Median age at CED was 5.0 years (IQR 1.4, 9.3 years) with the majority being non-Hispanic white (73%) males (70%). Median follow-up between CED and most recent encounter was 5.1 years (IQR 1.2, 6.8). Nephrology and Urology were the most common specialties involved in care, with low utilization of other sub-specialties (12%-36%). Most patients (82%) had diagnostic imaging used to evaluate kidney stones; 11 (33%) had studies of extra-renal involvement. Stone surgery was performed in 15 (46%) patients. Four patients (12%) required dialysis, begun in all prior to CED; four patients required renal or renal/liver transplant.    Conclusion: In this large cohort of U.S. PH children, patients required heavy health care utilization with room for improvement in involving multi-disciplinary specialists. What is Known: • Primary hyperoxaluria (PH) is rare with significant implications on patient health. Typical involvement includes the kidneys; however, extra-renal manifestations occur. • Most large population studies describe clinical manifestations and involve registries. What is New: • We report the clinical journey, particularly related to diagnostic studies, interventions, multispecialty involvement, and hospital utilization, of a large cohort of PH pediatric patients in the PEDSnet clinical research network. • There are missed opportunities, particularly in that of specialty care, that could help in the diagnosis, treatment, and even prevention of known clinical manifestations.

Caregiver disclosure of common early childhood pediatric urologic surgeries.

BACKGROUND: Certain pediatric urologic diagnoses can have serious long-term adverse health outcomes. As a result, it is important for a child to be aware of their diagnosis and a prior surgery. When children have surgery prior to the age of memory formation, it is incumbent upon their caregiver to disclose this surgery. When and how to disclose this information and even if this occurs, is not clear. OBJECTIVE: We developed a survey to assess caregiver plans to disclose early childhood pediatric urologic surgery and evaluate for predictors of disclosure and resources needed. METHODS: A questionnaire was distributed to caregivers of male children ≤4 years old undergoing single stage repair of hypospadias, inguinal hernia, chordee, or cryptorchidism as part of an IRB approved research study. These surgeries were chosen due to being outpatient surgeries with potential long-term complications and impact. The age criteria was chosen due to likely being before patient memory formation and thus reliance on caregiver disclosure of prior surgery. Surveys were collected the day of surgery and contained information on caregiver demographics, validated health literacy screening, and plans to disclose surgery. RESULTS: 120 survey responses were collected (Summary Table). The majority of caregivers responded affirmatively to planning to disclose their child's surgery (108; 90%). There was no impact of caregiver age, gender, race, marital status, education level, health literacy, or personal surgical history on plans to disclose surgery (p ≥ 0.05). Plan to disclose was also not different across urologic surgery type. Race was significantly associated with being "concerned or nervous about disclosing the surgery to the patient". The median patient age for planned disclosure was 10 years (IQR: 7-13). Only 17 respondents (14%) stated they received any information about how to discuss this surgery with the patient, however 83 (69%) felt this information would be helpful. CONCLUSIONS: Our study suggests that most caregivers plan to discuss early childhood urologic surgeries with children, however want further guidance in how to talk to their child. While no specific surgery or demographic factor was found to be significantly associated with plans to disclose surgery, it is concerning that one in ten patients will potentially never learn about impactful surgery they had as a child. There is an opportunity for us to better counsel our patients' families about surgical disclosure and fill this gap with quality improvement efforts.

Ureteral Stent Placement Prior to Definitive Stone Treatment Is Associated With Higher Postoperative Emergency Department Visits and Opioid Prescriptions for Youth Having Ureteroscopy or Shock Wave Lithotripsy.

PURPOSE: Little is known about the impact of ureteral stents on youth having stone surgery. We evaluated the association of ureteral stent placement before or concurrent with ureteroscopy and shock wave lithotripsy with emergency department visits and opioid prescriptions among pediatric patients. MATERIALS AND METHODS: We conducted a retrospective cohort study of individuals aged 0-24 years who underwent ureteroscopy or shock wave lithotripsy from 2009-2021 at 6 hospitals in PEDSnet, a research network that aggregates electronic health record data from children's health systems in the United States. The exposure, primary ureteral stent placement, was defined as a stent placed concurrent with or within 60 days before ureteroscopy or shock wave lithotripsy. Associations between primary stent placement and stone-related ED visits and opioid prescriptions within 120 days of the index procedure were evaluated with mixed-effects Poisson regression. RESULTS: Two-thousand ninety-three patients (60% female; median age 15 years, IQR 11-17) had 2,477 surgical episodes; 2,144 were ureteroscopy and 333 were shock wave lithotripsy. Primary stents were placed in 1,698 (79%) ureteroscopy episodes and 33 (10%) shock wave lithotripsy episodes. Ureteral stents were associated with a 33% higher rate of emergency department visits (IRR 1.33; 95% CI 1.02-1.73) and a 30% higher rate of opioid prescriptions (IRR 1.30; 95% CI 1.10-1.53). The magnitudes of both associations were greater for shock wave lithotripsy. Results were similar for age <18 and were lost when restricted to concurrent stent placement. CONCLUSIONS: Primary ureteral stent placement was associated with more frequent emergency department visits and opioid prescriptions, driven by pre-stenting. These results support elucidating situations where stents are not necessary for youth with nephrolithiasis.

Reducing Opioid Prescriptions after Common Outpatient Pediatric Urologic Surgeries: A Quality Improvement Assessment.

Pediatric patients undergoing outpatient surgeries often receive prescriptions for postoperative pain, including opioid medications. As a result, the American Academy of Pediatrics formally challenged all pediatric surgeons to decrease opioid prescribing for common specialty-specific outpatient procedures at discharge. To meet this challenge, we designed a quality improvement project to decrease the average number of opioid doses administered to pediatric patients undergoing 3 common outpatient urologic surgeries: circumcision, orchiopexy, and inguinal hernia repair (IHR). Methods: We formally challenged providers at our institution to reduce opioid doses per prescription and administration to patients overall. We performed a retrospective chart review at our single pediatric institution to establish baseline opioid prescribing values from July 2017 to March 2018. We aimed to reduce this value by 50% in 6 months and sustain this decrease throughout the project duration. Results: We performed 1,518 orchiopexies, 1,505 circumcisions, and 531 IHRs. The percent change in the average number of opioid doses prescribed per patient from baseline values assessed to 2021 was statistically significant for orchiopexies (P < 0.0001), IHRs (P < 0.0001), and circumcisions (P < 0.0001). In addition, the change in the percentage of patients prescribed opioids from baseline was statistically significant for all 3 procedures (P < 0.001). Conclusions: This project demonstrated that through an organized quality improvement initiative, the average number of opioid medications prescribed and the total percentage of patients prescribed opioids following common outpatient pediatric urologic procedures can be decreased by at least 50% and sustained through project duration.