Reactive oxygen species, electrode potential and pH affect CoCrMo alloy corrosion and semiconducting behavior in simulated inflammatory environments.

Crevice corrosion in modular taper junctions of hip or knee replacements using cobalt-chrome-molybdenum (CoCrMo) alloys remains a clinical concern. Non-mechanically-driven corrosion has been less explored compared to mechanically assisted crevice corrosion. This study hypothesized that solution chemistry within crevices, inflammation, and cathodic electrode potential shifts during fretting result in low pH and generate reactive oxygen species (ROS), affecting oxide film behavior. This study investigated how resistance and capacitance of the CoCrMo oxide film (i.e., corrosion resistance) are modified in simulated in vivo crevice environments of modular taper junctions. Six solutions were evaluated (two pH levels: 1 and 7.4 and four hydrogen peroxide (H2O2) concentrations: 0, 0.001, 0.01 and 0.1 M). Rp versus voltage and Mott-Schottky plots were created from symmetry-based electrochemical impedance spectroscopy (sbEIS). At pH 1, the semiconductor transition to p-type occurs at more anodic potentials and higher flat band potentials were found. H2O2 decreased the flat band potential and slope in the Mott-Schottky plot. Higher H2O2 in pH 7.4 solution significantly modified the oxide film, leading to increased donor density (p = 0.0004) and a 150-fold reduction in Rp in the cathodic potential range at -1 V (p = 0.0005). The most unfavorable condition (0.1 M H2O2 pH 1) resulted in a 250-fold lower resistance compared to phosphate buffered saline (PBS) pH 7.4 at -1 V (p = 0.0013). This study highlights the corrosion susceptibility of CoCrMo under adverse chemical and potential conditions, identifying increased defects in the oxide film due to ROS, hydrogen ions and electrode potential. STATEMENT OF SIGNIFICANCE: Corrosion of cobalt chrome molybdenum alloy caused by direct chemical attack in the crevice region of hip replacements, such as modular taper junctions, remains a clinical concern. The junction environment contains adverse chemical compositions, including high acidity and reactive oxygen species (ROS) due to inflammatory responses against the corrosion products. We simulate inflammatory environments with different pH levels and hydrogen peroxide, representative of ROS. We employ electrochemical impedance spectroscopy and apply stepwise voltage over the range induced by tribocorrosion processes. We relate the effect of adverse chemical components on corrosion and semiconducting behavior of the oxide film using Mott-Schottky analysis. This study shows how pH and ROS concentration compromises the oxide film potentially leading to non-mechanically induced corrosion.

Titanium-Titanium Junctions in the Knee Corrode, Generating Damage Similar to the Hip.

BACKGROUND: Previous studies identified corrosion between the modular tibial components of total knee arthroplasty devices. However, gaps persist. Compared to the hip, damage modes that occur within taper junctions in the knee remain poorly understood. In this study, we investigated corrosion on total knee arthroplasty components with titanium-titanium junctions. We asked the following question: under typical in vivo cyclic loading conditions, will the same alloy damage modes from total knee arthroplasty devices resemble those documented in the hip? METHODS: A total of 50 paired titanium alloy tibial baseplates and stems were collected and semiquantitatively analyzed using Goldberg corrosion scoring. To characterize damage, a subsection of moderately and severely corroded components was sectioned and imaged using scanning electron and digital optical microscopy. RESULTS: Of the 100 device components, 95% showed visual evidence of corrosion. The initial contact area between the stem and bore generally occurred 3 mm from the stem taper base. Scanning electron microscopy revealed 4 damage modes, including oxide film formation, crevice corrosion, selective dissolution, and pitting. CONCLUSIONS: Each of the damage modes identified in modular titanium-titanium tibial junctions was previously reported by total hip arthroplasty retrieval studies. Cumulatively, our results suggest that mechanically assisted crevice corrosion promoted this damage in vivo.

Increasing temperature accelerates Ti-6Al-4V oxide degradation and selective dissolution: An Arrhenius-based analysis.

Ti-6Al-4V selective dissolution occurs in vivo on orthopedic implants as the leading edge of a pitting corrosion attack. A gap persists in our fundamental understanding of selective dissolution and pre-clinical tests fail to reproduce this damage. While CoCrMo clinical use decreases, Ti-6Al-4V and the crevice geometries where corrosion can occur remain ubiquitous in implant design. Additionally, most additively manufactured devices cleared by the FDA use Ti-6Al-4V. Accelerated preclinical testing, therefore, would aid in the evaluation of new titanium devices and biomaterials. In this study, using temperature, we (1) developed an accelerated pre-clinical methodology to rapidly induce dissolution and (2) investigated the structure-property relationship between the dissolving surface and the oxide layer. We hypothesized that solution temperature and H2O2 concentration would accelerate oxide degradation, increase corrosion kinetics and decrease experimental times. To assess this effect, we selected temperatures above (45 °C), below (24 °C), and at (37 °C) physiological levels. Then, we acquired electrochemical impedance spectra during active ß dissolution, showing significant decreases in oxide polarization resistance (Rp) both over time (p = 0.000) and as temperature increased (p = 0.000). Next, using the impedance response as a guide, we quantified the extent of selective dissolution in scanning electron micrographs. As the temperature increased, the corrosion rate increased in an Arrhenius-dependent manner. Last, we identified three surface classes as the oxide properties changed: undissolved, transition and dissolved. These results indicate a concentration and temperature dependent structure-property relationship between the solution, the protective oxide film, and the substrate alloy. Additionally, we show how supraphysiological temperatures induce structurally similar dissolution to tests run at 37 °C in less experimental time. STATEMENT OF SIGNIFICANCE: Within modular taper junctions of total hip replacement systems, retrieval studies document severe corrosion including Ti-6AL-4V selective dissolution. Current pre-clinical tests and ASTM standards fail to reproduce this damage, preventing accurate screening of titanium-based biomaterials and implant designs. In this study, we induce selective dissolution using accelerated temperatures. Building off previous work, we use electrochemical impedance spectroscopy to rapidly monitor the oxide film during dissolution. We elucidate components of the dissolution mechanism, where oxide degradation precedes pit nucleation within the ß phase. Using an Arrhenius approach, we relate these accelerated testing conditions to more physiologically relevant solution concentrations. In total, this study shows the importance of including adverse electrochemical events like cathodic activation and inflammatory species in pre-clinical testing.

Urology Mythbusters: Does prevalence of vesicoureteral reflux in children vary by race?

In this edition of Mythbusters, we examine the premise that prevalence of vesicoureteral reflux (VUR) in children varies by race. Specifically, we consider whether there is evidence supporting the contention that VUR is more common in White children and less common in Black children. Statements regarding the lower prevalence of VUR in Black children are ubiquitous in both research papers and reviews. Many of the references cited in support of these statements do not actually support the existence of racial variation in VUR, due to uncontrolled single-arm study designs, highly selected samples at risk for bias, or simply not addressing VUR prevalence at all. There is a small group of studies which directly compared VUR prevalence among children undergoing cystography, and these studies have found VUR to be less common among Black children compared to White children. However, the results of such papers can only be considered in the context of a system in which systemic bias and racism may impact access and care delivery in profound ways. Given that race is a social construct that bears little relationship to shared genetic ancestry or underlying biological characteristics, these findings must be approached with extreme caution. The goals of pediatric urological care should be to confer equitable care to all young children regardless of race.

Fretting and Fretting Corrosion Behavior of Additively Manufactured Ti-6Al-4V and Ti-Nb-Zr Alloys in Air and Physiological Solutions.

Additive manufacturing (AM) of orthopedic implants has increased in recent years, providing benefits to surgeons, patients, and implant companies. Both traditional and new titanium alloys are under consideration for AM-manufactured implants. However, concerns remain about their wear and corrosion (tribocorrosion) performance. In this study, the effects of fretting corrosion were investigated on AM Ti-29Nb-21Zr (pre-alloyed and admixed) and AM Ti-6Al-4V with 1% nano yttria-stabilized zirconia (nYSZ). Low cycle (100 cycles, 3 Hz, 100 mN) fretting and fretting corrosion (potentiostatic, 0 V vs. Ag/AgCl) methods were used to compare these AM alloys to traditionally manufactured AM Ti-6Al-4V. Alloy and admixture surfaces were subjected to (1) fretting in the air (i.e., small-scale reciprocal sliding) and (2) fretting corrosion in phosphate-buffered saline (PBS) using a single diamond asperity (17 µm radius). Wear track depth measurements, fretting currents and scanning electron microscopy/energy dispersive spectroscopy (SEM/EDS) analysis of oxide debris revealed that pre-alloyed AM Ti-29Nb-21Zr generally had greater wear depths after 100 cycles (4.67 +/- 0.55 µm dry and 5.78 +/- 0.83 µm in solution) and higher fretting currents (0.58 +/- 0.07 µA). A correlation (R2 = 0.67) was found between wear depth and the average fretting currents with different alloys located in different regions of the relationship. No statistically significant differences were observed in wear depth between in-air and in-PBS tests. However, significantly higher amounts of oxygen (measured by oxygen weight % by EDS analysis of the debris) were embedded within the wear track for tests performed in PBS compared to air for all samples except the ad-mixed Ti-29Nb-21Zr (p = 0.21). For traditional and AM Ti-6Al-4V, the wear track depths (dry fretting: 2.90 +/- 0.32 µm vs. 2.51 +/- 0.51 µm, respectively; fretting corrosion: 2.09 +/- 0.59 µm vs. 1.16 +/- 0.79 µm, respectively) and fretting current measurements (0.37 +/- 0.05 µA vs. 0.34 +/- 0.05 µA, respectively) showed no significant differences. The dominant wear deformation process was plastic deformation followed by cyclic extrusion of plate-like wear debris at the end of the stroke, resulting in ribbon-like extruded material for all alloys. While previous work documented improved corrosion resistance of Ti-29Nb-21Zr in simulated inflammatory solutions over Ti-6Al-4V, this work does not show similar improvements in the relative fretting corrosion resistance of these alloys compared to Ti-6Al-4V.

Oxide degradation precedes additively manufactured Ti-6Al-4V selective dissolution: An unsupervised machine learning correlation of impedance and dissolution compared to Ti-29Nb-21Zr.

Additively manufactured (AM) Ti-6Al-4V devices are implanted with increasing frequency. While registry data report short-term success, a gap persists in our understanding of long-term AM Ti-6Al-4V corrosion behavior. Retrieval studies document ß phase selective dissolution on conventionally manufactured Ti-6Al-4V devices. Researchers reproduce this damage in vitro by combining negative potentials (cathodic activation) and inflammatory simulating solutions (H2 O2 -phosphate buffered saline). In this study, we investigate the effects of these adverse electrochemical conditions on AM Ti-6Al-4V impedance and selective dissolution. We hypothesize that cathodic activation and H2 O2 solution will degrade the oxide, promoting corrosion. First, we characterized AM Ti-6Al-4V samples before and after a 48 h -0.4 V hold in 0.1 M H2 O2 /phosphate buffered saline. Next, we acquired nearfield electrochemical impedance spectroscopy (EIS) data. Finally, we captured micrographs and EIS during dissolution. Throughout, we used AM Ti-29Nb-21Zr as a comparison. After 48 h, AM Ti-6Al-4V selectively dissolved. Ti-29Nb-21Zr visually corroded less. Structural changes at the AM Ti-6Al-4V oxide interface manifested as property changes to the impedance. After dissolution, the log-adjusted constant phase element (CPE) parameter, Q, significantly increased from -4.75 to -3.84 (Scm-2 (s)α ) (p = .000). The CPE exponent, α, significantly decreased from .90 to .84 (p = .000). Next, we documented a systematic decrease in oxide polarization resistance before pit nucleation and growth. Last, using k-means clustering, we established a structure-property relationship between impedance and the surface's dissolution state. These results suggest that AM Ti-6Al-4V may be susceptible to in vivo crevice corrosion within modular taper junctions.

Successful Adolescent Varicocelectomy Improves Total Motile Sperm Count.

BACKGROUND: Management of the adolescent varicocele focuses on optimizing fertility potential, but to date there is limited data on the success of varicocelectomy on optimizing semen parameters for individual adolescent patients. We reviewed our database of over 1600 adolescent varicocele patients to find those with pre- and postoperative semen analyses to determine the impact of varicocele correction. METHODS: 15 Tanner stage V patients with unilateral clinically apparent left-sided with pre- and postoperative semen analyses were identified. Mixed models were used to compare semen parameters pre- and post-varicocelectomy in patients with successful management. RESULTS: Complete elimination of the varicocele was achieved in 12/15 (80%) patients. Three patients had persistent varicocele (with down-grading in two) and declined further intervention. Median time between pre- and postoperative semen analyses was 24.2 months. For those with successful varicocele correction, total motile sperm count (TMSC) improved in all but one (Figure 1), with an average increase of 44.0 million (95% CI: 18.7-69.3) in post-varicocelectomy analyses compared to pre-varicocelectomy (p = 0.0016). Mean percent improvement was 649.2%. It went from abnormal to normal (≥20 million/cc) in 55.6% (5/9). For the three patients with persistent varicocele, one had improved TMSC from abnormal to normal range, one had worsening within normal range, and one had effectively no change. CONCLUSION: Successful correction of adolescent varicocele may improve TMSC. In over half of our institution's cases, an abnormal value normalized. Surgical intervention may be considered for adolescent varicoceles associated with abnormal semen parameters. LEVELS OF EVIDENCE: Level III. TYPE OF STUDY: Treatment study.

Prenatal Diagnoses and Intervention.

Fetal upper tract urinary system dilation is one of the most common findings on prenatal ultrasonography. Rarely, this may represent fetal lower urinary tract obstruction (LUTO), of which posterior urethral valves are the predominant etiology. LUTO is the most dire fetal urologic diagnosis, as it affects not only the baby's management after birth but sometimes the course of the pregnancy itself. A variety of treatment options are available prenatally; these include observation, vesicoamniotic shunt placement, amnioinfusion, and attempts at direct treatment of the valves themselves. All fetal interventions carry substantial risks; caution should attend every discussion of treatment.

Genital Manifestations of Physical Abuse in Male Infants and Children.

We present 3 male patients with genital bruising due to physical abuse to improve recognition of genital trauma as a sentinel injury. In the absence of an underlying medical condition or a clear acceptable accidental mechanism for the genital injury, an evaluation for child abuse is recommended.

Additively manufactured Ti-29Nb-21Zr shows improved oxide polarization resistance versus Ti-6Al-4V in inflammatory simulating solution.

Retrieval studies in the past two decades show severe corrosion of titanium and its alloys in orthopedic implants. This damage is promoted by mechanically assisted crevice corrosion (MACC), particularly within modular titanium-titanium junctions. During MACC, titanium interfaces may be subject to negative potentials and reactive oxygen species (ROS), generated from cathodic activation and/or inflammation. Additive manufacturing (AM) may be able to produce new, corrosion-resistant titanium alloys and admixtures that are less susceptible to these adverse electrochemical events. In this study, we characterize the impedance and corrosion properties of three new AM titanium materials, including Ti-6Al-4V with added 1% nano-yttria stabilized ZrO2 , admixed Ti-29Nb-21Zr, and pre-alloyed Ti-29Nb-21Zr. We aim to elucidate how these materials perform when subjected to high ROS solutions. We include conventionally and additively manufactured Ti-6Al-4V in our study as comparison groups. A 0.1 M H2 O2 phosphate-buffered saline (PBS) solution, simulating inflammatory conditions, significantly increased biomaterial OCP (-0.14 V vs. Ag/AgCl) compared to PBS only (-0.38 V, p = .000). During anodic polarization, Ti-6Al-4V passive current density more than doubled from 1.28 × 10-7 to 3.81 × 10-7 A/cm2 when exposed to 0.1 M H2 O2 . In contrast, Ti-29Nb-21Zr passive current density remained relatively unchanged, slightly increasing from 7.49 × 10-8 in PBS to 9.31 × 10-8 in 0.1 M H2 O2 . Ti-29Nb-21Zr oxide polarization resistance (Rp ) was not affected by 0.1 M H2 O2 , maintaining a high value (1.09 × 106 vs. 1.89 × 106 Ω cm2 ), while Ti-6Al-4V in 0.1 M H2 O2 solution had significantly diminished Rp (4.38 × 106 in PBS vs. 7.24 × 104 Ω cm2 in H2 O2 ). These results indicate that Ti-29Nb-21Zr has improved corrosion resistance in ROS containing solutions when compared with Ti-6Al-4V based biomaterials.

Is cerebral palsy associated with successful ureteral access during the initial attempt at ureteroscopy for urolithiasis in children and young adults?

BACKGROUND: Ureteroscopy is a common treatment for urolithiasis, but initial ureteral access is not always possible, particularly in pediatrics. Clinical experience suggests that neuromuscular conditions such as cerebral palsy (CP) may facilitate access, thus avoiding the need for pre-stenting and staged procedures. OBJECTIVE: We sought to determine if probability of successful ureteral access (SUA) during initial attempted ureteroscopy (IAU) is higher in pediatric patients with CP vs. without CP. STUDY DESIGN: We reviewed IAU cases for urolithiasis (2010-2021) at our center. Patients with pre-stenting, prior ureteroscopy, or urologic surgical history were excluded. CP was defined using ICD-10 codes. SUA was defined as scope access to urinary tract level sufficient to reach stone. Association of CP and other factors with SUA were evaluated. RESULTS: 230 patients (45.7% male, median age: 16 years [IQR: 12-18 y], 8.7% had CP) underwent IAU, with SUA in 183 (79.6%). SUA occurred in 90.0% of patients with CP vs. 78.6% of those without CP (p = 0.38). SUA was 81.7% in patients >12 years (vs. 73.8% in those <12), and the highest SUA was in those >12 years with CP (93.3%), but these differences were not statistically significant. Renal stone location was significantly associated with lower SUA (p = 0.007). Among patients with renal stone only, SUA in those with CP was 85.7% vs. 68.9% in those without CP (p = 0.33). SUA did not differ significantly by gender or BMI. CONCLUSIONS: CP may facilitate ureteral access during IAU in pediatric patients, but we were unable to show a statistically significant difference. Further study of larger cohorts may demonstrate whether CP or other patient factors are associated with successful initial access. Improved understanding of such factors would help preoperative counseling and surgical planning for children with urolithiasis.

Predicting Corrosion Damage in the Human Body Using Artificial Intelligence: In Vitro Progress and Future Applications.

Artificial intelligence (AI) is used in the clinic to improve patient care. While the successes illustrate AI's impact, few studies have led to improved clinical outcomes. In this review, we focus on how AI models implemented in nonorthopedic fields of corrosion science may apply to the study of orthopedic alloys. We first define and introduce fundamental AI concepts and models, as well as physiologically relevant corrosion damage modes. We then systematically review the corrosion/AI literature. Finally, we identify several AI models that may be implemented to study fretting, crevice, and pitting corrosion of titanium and cobalt chrome alloys.

Hybrid Clinics: A New Model for Ambulatory Care to Reduce Infection Risk.

Objectives: To assess the viability of a hybrid clinic model combining in-person examination with video-based consultation to minimize viral transmission risk. Methods: Data were collected prospectively in a pediatric urology clinic for in-person visits from January to April 2018 ("classic") and hybrid visits from October to December 2020 of the COVID-19 pandemic ("hybrid"). Variables included provider, diagnosis, patient type, time of day, prior surgery, postoperative status, and decision-making for surgery. The primary outcome was "room time" or time in-person. The secondary outcome was "total time" or visit duration. Proportion of visits involving close contact (room time ≥15 min) was assessed. Univariate analyses were performed using the Wilcoxon rank-sum test and Fisher's exact test. Mixed models were fitted for visit approach and other covariates as fixed effects and provider as random effect. Results: Data were collected for 346 visits (256 classic, 90 hybrid). Hybrid visits were associated with less room time (median 3 min vs. 10 min, p < 0.001) but greater total time (median 13.5 min vs. 10 min, p = 0.001) as compared with classic visits. On multivariate analysis, hybrid visits were associated with 3 min less room time (95% confidence intervals [CIs]: -5.3 to -1.7, p < 0.001) but 3.8 min more total time (95% CI: 1.5-6.1, p = 0.001). Close contact occurred in 6.7% of hybrid visits, as compared with 34.8% of classic visits (p < 0.001). Conclusions: Hybrid clinic visits reduce room time as compared with classic visits. This approach overcomes the examination limitations of telemedicine while minimizing viral transmission, and represents a viable model for ambulatory care whenever close contact carries infection risk.

Cathodic activation and inflammatory species are critical to simulating in vivo Ti-6Al-4V selective dissolution.

In vivo retrievals of metallic orthopedic implants have shown selective dissolution of Ti-6Al-4V, where the vanadium-rich ß phase preferentially corrodes from the surface. This damage, typically observed in crevices, is not directly caused by wear mechanics and the underlying electrochemical mechanism remains poorly understood. Previous studies show that fretting corrosion can cause negative potential drops, resulting in a decrease in surface oxide passivation resistance and the electrochemical generation of reactive oxygen species (ROS) at metallic surfaces. In this study, we combine cathodic activation and hydrogen peroxide to induce selective dissolution in vitro. After a 600 s -1 V hold and 4 h recovery in 20 °C 1 M H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; solution, the Ti-6Al-4V ß phase was preferentially dissolved. An initial activation threshold of -0.5 V induced a significant increase in ß dissolution (p = 0.000). Above this threshold, little selective dissolution occurred. In an Arrhenius-like fashion, decreasing solution concentration to 0.1 M required 72 h to generate ß dissolution instead of 4 h at 1 M. Heating 0.1 M solution to body temperature (37 °C) resulted in a decrease in the time needed to replicate a similar level of ß dissolution (&amp;gt;90%). Electrochemical impedance shows that both cathodic activation and inflammatory species are necessary to induce selective dissolution, where the combinatorial effect causes a significant drop in oxide passivation resistance from 10&lt;sup&gt;6&lt;/sup&gt; to 10&lt;sup&gt;2&lt;/sup&gt; (p = 0.000). STATEMENT OF SIGNIFICANCE: Though hip arthroplasties are considered a successful procedure, revision rates of 2-4% result in tens of thousands of additional surgeries within the United States, subjecting patients to increased risk of complications. Corrosion is associated with implant failure and retrieval studies show that titanium and its alloys can severely corrode in vivo in ways not yet duplicated in vitro. Here, we reproduce selective dissolution of Ti-6Al-4V ß phase simulating key characteristics of in vivo degradation observed in orthopedic retrievals. We establish both cathodically activated corrosion, a relatively unexplored concept, and the presence of inflammatory species as prerequisites, furthering our understanding of this clinically relevant damage mode. We introduce an Arrhenius-based approach to assess the concentration-temperature-time interactions present.

Comparing Pediatric Ureteroscopy Outcomes with SuperPulsed Thulium Fiber Laser and Low-Power Holmium:YAG Laser.

PURPOSE: The thulium fiber laser is a promising new lithoptripsy technology never before studied in the pediatric population. Our center adopted the first platform in North America, the SuperPulsed thulium fiber laser (SPTF). We aimed to compare outcomes in pediatric ureteroscopy using the SPTF to those using the gold standard, low-power holmium:yttrium-aluminum-garnet (Ho:YAG) laser. MATERIALS AND METHODS: This is a retrospective, consecutive cohort study of unilateral ureteroscopy with laser lithotripsy performed in pediatric patients from 2016 to 2021 as an early adopter of the SPTF. Thirty-day complications and stone-free status, defined as the absence of a stone fragment on followup imaging within 90 days, were analyzed using logistic regression. Operative times were compared using linear regression. Propensity scores for use of SPTF were used in regression analyses to account for potential cohort imbalance. RESULTS: A total of 125 cases were performed in 109 pediatric patients: 93 with Ho:YAG and 32 with SPTF. No significant difference was noted in age (p=0.2), gender (p=0.6), stone burden (p >0.9) or stone location (p=0.1). The overall stone-free rate was 62%; 70% with SPTF and 59% with Ho:YAG. The odds of having a residual stone fragment were significantly lower with SPTF than with Ho:YAG (OR=0.39, 95% CI: 0.19-0.77, p=0.01). There was no significant difference in operative time (p=0.8). Seven (25%) complications were noted with SPTF and 19 (22%) with Ho:YAG (p=0.6). CONCLUSIONS: The SPTF laser was associated with a higher stone-free rate than the low-power Ho:YAG laser without compromising operative time and safety.

Primary hyperoxaluria type 1: urologic and therapeutic management.

While the surgical approaches available in primary hyperoxaluria (PH) are common to all patients requiring intervention for urolithiasis, the indications for treatment and their corresponding toxicities are unique. Being a rare disease, we are guided by case series. This review summarizes the available literature highlighting the important disease-specific considerations. Shockwave lithotripsy (SWL) is of particular interest. It is generally the first-line treatment for stones in children, but here the stones produced will be relatively resistant to fragmentation. In addition, there are concerning reports in children of sudden unilateral decline in function in the treated kidney as measured by nuclear renography. Percutaneous nephrostolithotomy might intuitively seem favorable given the shortest drain duration and the ability to treat larger stones efficiently but, similar to SWL, rapid chronic kidney disease (CKD) progression has been seen postoperatively. Ureteroscopy is therefore generally the safest option, but considerations regarding stent encrustation, the growth of residual fragments and the large volume of stone often faced may limit this approach. The surgeon must balance the above with consideration of the patient's CKD status when considering a plan of monitoring and treating stones in PH.

Comparative effectiveness of paediatric kidney stone surgery (the PKIDS trial): study protocol for a patient-centred pragmatic clinical trial.

INTRODUCTION: The strength of the evidence base for the comparative effectiveness of three common surgical modalities for paediatric nephrolithiasis (ureteroscopy, shockwave lithotripsy and percutaneous nephrolithotomy) and its relevance to patients and caregivers are insufficient. We describe the methods and rationale for the Pediatric KIDney Stone (PKIDS) Care Improvement Network Trial with the aim to compare effectiveness of surgical modalities in paediatric nephrolithiasis based on stone clearance and lived patient experiences. This protocol serves as a patient-centred alternative to randomised controlled trials for interventions where clinical equipoise is lacking. METHODS AND ANALYSIS: The PKIDS is a collaborative learning organisation composed of 26 hospitals that is conducting a prospective pragmatic clinical trial comparing the effectiveness of ureteroscopy, shockwave lithotripsy and percutaneous nephrolithotomy for youth aged 8-21 years with kidney and/or ureteral stones. Embedded within clinical care, the PKIDS trial will collect granular patient-level, surgeon-level and institution-level data, with a goal enrolment of 1290 participants over a 21-month period. The primary study outcome is stone clearance, defined as absence of a residual calculus of >4 mm on postoperative ultrasound. Secondary outcomes include patient-reported physical, emotional and social health outcomes (primarily using the Patient-Reported Outcome Measurement Information System), analgesic use and healthcare resource use. Timing and content of secondary outcomes assessments were set based on feedback from patient partners. Heterogeneity of treatment effect for stone clearance and patient-reported outcomes by participant and stone characteristics will be assessed. ETHICS AND DISSEMINATION: This study is approved by the central institutional review board with reliance across participating sites. Participating stakeholders will review results and contribute to development dissemination at regional, national and international meetings. TRIAL REGISTRATION NUMBER: NCT04285658; Pre-results.