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The COVID-19 pandemic will leave an indelible mark on the careers of current medical trainees. Given the disruptions to medical education, economic impact on institutions, and the uncertainties around future job prospects, trainees are facing unprecedented challenges. This situation is especially concerning for futures of pediatric physician-scientist trainees, where concerns regarding maintaining the pipeline were well documented prior to the emergence of COVID-19. In this Perspectives article, we leverage the unique expertise of our workgroup to address concerns of physician-scientist trainees and to provide suggestions on how to navigate career trajectories in the post-COVID-19 era. We identified and addressed four major areas of concern: lack of in-person conferences and the associated decrease access to mentors and networking activities, decreased academic productivity, diminished job prospects, and mental health challenges. We also suggest actions for trainees, mentors and educational leaders, and institutions to help support trainees during the pandemic, with a goal of maintaining the pediatric physician-scientist pipeline.

Urobiome research has the potential to advance the understanding of a wide range of diseases, including lower urinary tract symptoms and kidney disease. Many scientific areas have benefited from early research method consensus to facilitate the greater, common good. This consensus document, developed by a group of expert investigators currently engaged in urobiome research (UROBIOME 2020 conference participants), aims to promote standardization and advances in this field by the adoption of common core research practices. We propose a standardized nomenclature as well as considerations for specimen collection, preservation, storage, and processing. Best practices for urobiome study design include our proposal for standard metadata elements as part of core metadata collection. Although it is impractical to follow fixed analytical procedures when analyzing urobiome data, we propose guidelines to document and report data originating from urobiome studies. We offer this first consensus document with every expectation of subsequent revision as our field progresses.

The microbial ecosystem within the bladder that can be measured within the urine, or urobiome, is an emerging field of study with little published data regarding children. However, investigations into urobiome research have the potential to significantly impact the understanding of the pathophysiology of genitourinary conditions, as well as potentially identify novel therapeutics. Therefore, both researchers and clinicians should be aware of pediatric urobiome research. The purpose of this review is to highlight the literature around urobiome research in urinary tract infections, nephrolithiasis, and neurogenic bladder; comment on pediatric-specific considerations when reading and interpreting the urobiome literature; and to identify new potential areas of research., Author(s): Elisabeth Cole [sup.1] , Nader Shaikh [sup.1] , Catherine S. Forster [sup.1] Author Affiliations: (1) grid.21925.3d, 0000 0004 1936 9000, Department of Pediatrics, University of Pittsburgh School of Medicine, [...]

Background The sensitivity and specificity of the leukocyte esterase test for the diagnosis of urinary tract infection (UTI) are suboptimal. Recent studies have identified markers that appear to more accurately differentiate children with and without UTI. The objective of this study was to determine the accuracy of these markers, which included CCL3, IL-8, CXCL1, TNF-alpha, IL-6, IFN-gamma, IL-17, IL-9, IL-2, and NGAL, in the diagnosis of UTI. Methods This was a prospective cross-sectional study to compare inflammatory proteins between urine samples from febrile children with a UTI, matched febrile controls without a UTI, and asymptomatic healthy controls. Results We included 192 children (75 with febrile UTI, 69 febrile controls, and 48 asymptomatic healthy controls). Urinary proteins that best discriminated between febrile children with and without UTI were NGAL, a protein that exerts a local bacteriostatic role in the urinary tract through iron chelation; CCL3, a chemokine involved in leukocyte recruitment; and IL-8, a cytokine involved in neutrophil recruitment. Levels of these proteins were generally undetectable in asymptomatic healthy children. Conclusions NGAL, CCL3, and IL-8 may be useful in the early diagnosis of UTI. Trial registration ClinicalTrials.gov (NCT01391793) Graphical abstract, Author(s): Nader Shaikh [sup.1] , Hui Liu [sup.1] , Marcia Kurs-Lasky [sup.1] , Catherine S Forster [sup.1] Author Affiliations: (1) grid.21925.3d, 0000 0004 1936 9000, Division of General Academic Pediatrics, [...]

Background Children who experience more than one urinary tract infection (UTI) are at increased risk of kidney scarring due to their UTIs. Girls are at especially high risk for developing kidney scarring as a result of recurrent UTIs. Prior work suggested that neutrophil gelatinase-associated lipocalin (NGAL) may be lower in children with recurrent UTI compared with those without. The objective of this work was to compare urine NGAL concentrations in matched urine samples in girls with single and recurrent UTIs. Methods Girls less than 6 years of age who presented with signs and symptoms of a UTI were eligible for enrollment. Both acute, obtained from residual urine collected as part of their clinical evaluation, and follow-up urine samples, obtained after the completion of antibiotics when the patient was in their usual state of health, were collected from patients. Acute and follow-up urine NGAL concentrations were compared between girls with single and recurrent UTIs, as well as those with negative cultures who served as controls. Results Seventy girls were included in this study, 6 controls, 43 single UTIs, and 20 girls with recurrent UTIs. Patients in the control group had lower median acute NGAL concentrations than either those with single or recurrent UTI. There were no differences in either acute or follow-up urine NGAL concentrations between those with single and recurrent UTIs. Conclusion In this cohort of girls less than 6 years of age, there is no difference in urine NGAL concentrations between those with single and recurrent UTIs., Author(s): Catherine S. Forster [sup.1] [sup.2] , Allison M. Loechtenfeldt [sup.1] , Samir S. Shah [sup.1] , Stuart Goldstein [sup.1] Author Affiliations: (1) grid.239573.9, 0000 0000 9025 8099, Department of [...]

Background Accurately diagnosing urinary tract infections (UTI) in children with neuropathic bladders can be difficult given the lack of specificity of both clinical symptoms and routine screening tests. We aimed to identify a priori unknown classes/groups of children with neuropathic bladder with respect to symptoms and UA results and examine their relationships with odds of UTI. Methods We used latent class analysis (LCA) to identify unobserved classes/groups of children with neuropathic bladder based on symptoms and urinalysis (UA) results, respectively. Demographic and clinical data were gathered by retrospective chart review of a cohort with neuropathic bladder. Symptoms and UA results were obtained by chart review of visits where urine culture was ordered. Results Around 193 patients were included in UA results analysis and 179 in symptom-based analysis. Two latent classes of patients were identified with respect to symptoms, labeled 'pyelonephritis class' and 'cystitis class,' and two, with respect to UA results, were labeled 'positive UA class' and 'negative UA class.' The pyelonephritis class had significantly higher odds of UTI compared to the asymptomatic class. While odds of UTI in cystitis class were higher than the asymptomatic class, this difference was not statistically significant. Positive UA class had significantly higher odds of UTI compared to negative UA class. Conclusion Two unobserved classes/groups exist in children with neuropathic bladder with respect to symptoms, corresponding to cystitis and pyelonephritis, and two classes of UA results that correspond with either a positive or negative UA. Our results suggest a differential approach to treatments may be considered., Author(s): Catherine S. Forster [sup.1] , Jichuan Wang [sup.2] [sup.3] Author Affiliations: (1) grid.239560.b, 0000 0004 0482 1586, Department of Pediatrics, Children's National Health System, , 111 Michigan Ave NW, [...]

Background Distinguishing between urinary tract infection (UTI) and colonization (UTC) in patients with neurogenic bladders who require clean intermittent catheterization (CIC) is difficult. Urinary neutrophil gelatinase-associated lipocalin concentrations (uNGAL) are increased in UTIs. Our objective was to determine the predictive accuracy of uNGAL for UTI in CIC-dependent children. Methods Cross-sectional study of CIC-dependent patients from August, 2015 to November, 2016. UTI was defined as (1) growth of [greater than or equal to] 50,000 cfu/mL of a uropathogen, (2) > 10 urinary white blood cells/hpf, and (3) [greater than or equal to] 2 of the following: temperature > 38 °C, abdominal pain, back pain, worsened incontinence, pain with catheterization, or malodorous/cloudy urine. Positive urine cultures that did not meet these criteria were grouped as UTC, and negative cultures were grouped as no growth. Results Two hundred one patients were included (no growth = 100, UTC = 77, UTI = 24). Median (interquartile range) uNGAL was higher in the UTI group (UTI 1361 (931, 2516) [mu]g/g creatinine, UTC 246 (106, 548) [mu]g/g creatinine, no growth 36 (11, 179) [mu]g/g creatinine, p < 0.01 for all comparisons). The area under the ROC curve for uNGAL for UTI versus no UTI was 0.89, 95% CI (0.80-0.98). Conclusion uNGAL is elevated in CIC-dependent children with UTI compared to those with negative cultures and those with UTC., Author(s): Catherine S. Forster [sup.1] , Elizabeth Jackson [sup.2] , Qing Ma [sup.1] , Michael Bennett [sup.1] , Samir S. Shah [sup.1] , Stuart L. Goldstein [sup.1] Author Affiliations: (Aff1) [...]

Introduction Children with recurrent urinary tract infections (rUTI) often show no identifiable cause of their infections. Neutrophil gelatinase-associated lipocalin (NGAL) is known to be upregulated within the uroepithelium and kidney of patients with UTI and exhibits a localized bacteriostatic effect through iron chelation. We hypothesize that some patients with rUTI without an identifiable cause of their recurrent infections have locally deficient NGAL production. We therefore explored whether a lack of NGAL production may be a factor in the pathogenesis of rUTI. Materials and methods Patients seen in the urology clinic for rUTI who were Results Fifteen cases and controls were enrolled. Median urinary NGAL levels were significantly decreased in rUTI patients compared with controls [15 (14-29) ng/ml vs 30 (27-61) ng/ml; p = 0.002)] Although comparatively diminished, measurable NGAL levels were present in all patients with rUTI. Conclusions Urinary NGAL is significantly decreased in patients with compared with patients without rUTI. These data suggest that some patients with rUTI may be predisposed to UTI because of a relative local deficiency in urinary NGAL production., Author(s): Catherine S. Forster [sup.1] [sup.2] , Kathryn Johnson [sup.3] , Viral Patel [sup.3] , Rebecca Wax [sup.4] , Nancy Rodig [sup.1] , Jonathan Barasch [sup.4] , Richard Bachur [sup.1] [...]

Neutrophil gelatinase-associated lipocalin (NGAL) is best known as a non-invasive early marker of acute kidney injury (AKI). However, recent published reports have described additional utility of both plasma NGAL (pNGAL) and urine NGAL (uNGAL) in various pathologic conditions within the pediatric urinary tract, including urinary tract infection, vesicoureteral reflux (VUR), renal scarring, and obstructive uropathy. These two forms of NGAL have different applications related to their mechanisms of upregulation: pNGAL can serve as a marker of systemic inflammatory conditions, whereas uNGAL is specific for insults to the renal epithelium. Therefore, pNGAL has good predictive accuracy in systemic inflammation associated with pyelonephritis and renal damage, while uNGAL is an effective marker for identifying infection within the genitourinary environment as well as subclinical renal damage as a result of scarring or obstruction. Continued work should focus on the effect of trending NGAL values in patients with pyelonephritis, VUR, and hydronephrosis, to determine if longitudinal NGAL patterns have value in predicting adverse outcomes., Author(s): Catherine S. Forster [sup.1] , Prasad Devarajan [sup.1] Author Affiliations: (1) 0000 0000 9025 8099grid.239573.9Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, 45229, Cincinnati, OH, USA [...]

Many proteins have been proposed to act as surrogate markers of organ damage, yet for many candidates the essential biomarker characteristics that link the protein to the injured organ have not yet been described. We generated an Ngal reporter mouse by inserting a double-fusion reporter gene encoding luciferase-2 and mCherry (Luc2-mC) into the Ngal (Lcn2) locus. The Ngal-Luc2-mC reporter accurately recapitulated the endogenous message and illuminated injuries in vivo in real time. In the kidney, Ngal-Luc2-mC imaging showed a sensitive, rapid, dose-dependent, reversible, and organ- and cell-specific relationship with tubular stress, which correlated with the level of urinary Ngal (uNgal). Unexpectedly, specific cells of the distal nephron were the source of uNgal. Cells isolated from Ngal-Luc2-mC mice also revealed both the onset and the resolution of the injury, and the actions of NF-kB inhibitors and antibiotics during infection. Thus, imaging of Ngal-Luc2-mC mice and cells identified injurious and reparative agents that affect kidney damage., Organ damage induces the appearance of many different proteins in serum and in urine, and some of these have been proposed as surrogate measures of tissue damage. However, such a [...]