High-Throughput in vitro Gel-Based Plate Assay to Screen for Calcium Oxalate Stone Inhibitors.

OBJECTIVE: Kidney stones are a common medical condition that is increasing in prevalence worldwide. Approximately, ∼80% of urinary calculi are composed of calcium oxalate (CaOx). There is a growing interest toward identifying therapeutic compounds that can inhibit the formation of CaOx crystals. However, some chemicals (e.g., antibiotics and bacterial metabolites) may directly promote crystallization. Current knowledge is limited regarding crystal promoters and inhibitors. Thus, we have developed an in vitro gel-based diffusion model to screen for substances that directly influence CaOx crystal formation. MATERIALS AND METHODS: We used double diffusion of sodium oxalate and calcium chloride-loaded paper disks along an agar medium to facilitate the controlled formation of monohydrate and dihydrate CaOx crystals. A third disk was used for the perpendicular diffusion of a test substance to assess its influence on CaOx crystal formation. RESULTS: We confirmed that citrates and magnesium are effective inhibitors of CaOx crystals. We also demonstrated that 2 strains of uropathogenic Escherichia coli are able to promote crystal formation. While the other tested uropathogens and most antibiotics did not change crystal formation, ampicillin was able to reduce crystallization. CONCLUSION: We have developed an inexpensive and high-throughput model to evaluate substances that influence CaOx crystallization.

Point-of-care ultrasonography for the diagnosis of testicular torsion: a practical resident curriculum.

Background: Prompt Doppler ultrasonography to aid in diagnosis is often key to managing testicular torsion, but there may be delays in access; a faster, more widely available alternative is point-of-care ultrasonography (POCUS). The purpose of this study was to develop and evaluate a scrotal POCUS curriculum for urology and emergency medicine residents. Methods: Content experts in urology, emergency medicine and diagnostic imaging collaborated in a modified Delphi method to design a practical didactic curriculum for scrotal POCUS for the identification of testicular torsion. Training included 3 online video teaching modules and a 1-hour hands-on teaching session with standardized adult patients. We evaluated participants' competency in scrotal POCUS using a validated scale. We assessed participants' knowledge, comfort and confidence in performing scrotal POCUS before and after the intervention and at 3 months. Results: Twenty-four urology (n = 12) and emergency medicine (n = 12) residents participated in the curriculum. After hands-on practice, 23 participants (96%) were deemed competent at scrotal POCUS. Pre-post testing showed significant improvement in knowledge (mean score 63% v. 80%, p < 0.001), comfort (mean Likert score 0.6 v. 3.6, p < 0.001) and confidence (mean Likert score 1.0 v. 2.1, p < 0.001) after the intervention. These effects were maintained at the 3-month assessment. Conclusion: The scrotal POCUS curriculum was effective and acceptable to both urology and emergency medicine residents. The findings suggest that scrotal POCUS can be learned effectively through a short hands-on session and didactic instruction.

Contexte: Le diagnostic rapide d'une torsion testiculaire à l'aide d'une échographie Doppler est souvent crucial à la prise en charge de ce trouble. Or, comme l'accès à cet examen peut être limité, l'échographie portable constitue une solution de rechange rapide et largement accessible. La présente étude visait la mise au point et l'évaluation d'un programme de formation sur l'échographie portable scrotale destiné aux résidents en urologie et en médecine d'urgence. Méthodes: Des experts en urologie, en médecine d'urgence et en imagerie diagnostique se sont servis d'une méthode Delphi modifiée pour concevoir un programme de formation sur l'échographie portable visant à faciliter le diagnostic de la torsion testiculaire. Ce programme comprenait 3 modules d'apprentissage vidéo en ligne, ainsi qu'une séance pratique d'une heure auprès de patients adultes normalisés. Nous avons évalué les compétences des participants en matière d'échographie portable scrotale au moyen d'une échelle validée. Nous avons également évalué les connaissances, l'aisance et le niveau de confiance des participants à l'égard de cet examen avant et immédiatement après la formation, puis 3 mois plus tard. Résultats: Au total, 24 résidents en urologie (n = 12) et en médecine d'urgence (n = 12) ont suivi le programme de formation. Après la séance pratique, 23 participants (96 %) avaient les compétences nécessaires à la réalisation d'une échographie portable scrotale. La comparaison des résultats obtenus avant et immédiatement après la formation a montré une augmentation significative des connaissances (note moyenne : 63 % c. 80 %; p < 0,001), de l'aisance (moyenne à l'échelle de Likert : 0,6 c. 3,6; p < 0,001) et du niveau de confiance (moyenne à l'échelle de Likert : 1,0 c. 2,1; p < 0,001) des participants. Les effets de la formation étaient toujours présents 3 mois plus tard. Conclusion: Le programme de formation sur l'échographie portable scrotale s'est avéré efficace et acceptable pour les résidents en urologie et en médecine d'urgence. Les résultats obtenus laissent croire qu'une formation pédagogique et une courte séance d'apprentissage pratique permettent l'enseignement efficace de l'échographie portable scrotale.

Population-based assessment of re-treatment and healthcare utilisation after photoselective vaporisation of the prostate or electrosurgical transurethral resection of the prostate.

OBJECTIVE: To compare the healthcare utilisation and repeat surgical treatment rate amongst older men undergoing an electrosurgical-transurethral resection of the prostate (TURP) vs photoselective vaporisation of the prostate (PVP), as the real-world implementation and outcomes of laser-based treatment have not been well studied. PATIENTS AND METHODS: We used administrative data from the province of Ontario, Canada, to identify all men aged >66 years who underwent their first electrosurgical-TURP/PVP between 2003 and 2016. Our primary exposure was type of procedure (PVP or electrosurgical-TURP). Our primary outcome was need for repeat surgical treatment. The primary analysis was an adjusted marginal Cox model approach, which accounted for clustering of patients within surgeons; adjusted hazard ratios (aHRs) or odds ratios (aORs) and 95% confidence intervals (CIs) are reported. RESULTS: We identified 52 748 men: 6838 (13%) underwent PVP, and 45 910 (87%) underwent electrosurgical-TURP. The median age was similar, and PVP became more common with time. Compared to the PVP group, more patients in the electrosurgical-TURP group had prior gross haematuria or urinary retention, and fewer had used anticoagulants, α-blockers, or 5α-reductase inhibitors. The need for repeat surgical treatment was significantly higher amongst men who had PVP (aHR 1.57, 95% CI 1.38-1.78; absolute risk difference +2.3%). PVP was also associated with a slightly higher risk of return to the emergency room within 30 days (aOR 1.11, 95% CI 1.01-1.22) and a significantly lower risk of blood transfusion (aOR 0.24, CI 0.16-0.37); the majority of PVP cases were done with a <24 h stay (73%) vs electrosurgical-TURP (7%). CONCLUSIONS: While some of the expected benefits of PVP (such as reduced transfusion risk and shorter length of stay) were observed, the significantly higher rate of repeat surgical treatment compared to electrosurgical-TURP may represent an important difference in implementation of this technology outside of clinical trials.

Daily therapy with a slow-releasing H2S donor GYY4137 enables early functional recovery and ameliorates renal injury associated with urinary obstruction.

OBJECTIVES: To assess the effects of slow-releasing H2S donor GYY4137 on post-obstructive renal function and injury following unilateral ureteral obstruction (UUO) by using the UUO and reimplantation (UUO-R) model in rats and to elucidate potential mechanisms by using an in vitro model of epithelial-mesenchymal transition (EMT). METHODS: Male Lewis rats underwent UUO at the left ureterovesical junction. From post-operative day (POD) 1-13, rats received daily intraperitoneal (IP) injection of phosphate buffered saline (PBS, 1 mL) or GYY4137 (200 µmol/kg/day in 1 mL PBS, IP). On POD 14, the ureter was reimplanted back into the bladder, followed by a right nephrectomy. Urine and serum samples were collected to monitor renal function. On POD 30, the left kidney was removed and tissue sections were stained with H&E, TUNEL, CD68, CD206, myeloperoxidase, and Masson's trichrome to determine cortical thickness, apoptosis, inflammation, and fibrosis. In our in vitro model of EMT, NRK52E cells were treated with 10 ng/mL TGF-ß1, 10 µM GYY4137 and/or 50 µM GYY4137. Western blot analysis was performed to determine the expression of E-cadherin, vimentin, Smad7 and TGF-ß1 receptor II (TßRII). RESULTS: GYY4137 led to a moderate decrease in post-obstructive serum creatinine, cystatin C and FENa. We also observed a trend towards a decrease in post-obstructive proteinuria following GYY4137 treatment. Histologically, we observed a significant decrease in apoptosis, inflammation, and fibrosis. Furthermore, our in vitro studies demonstrate that in the presence of TGF-ß1, GYY4137 significantly decreases vimentin and TßRII and significantly increases E-cadherin and Smad7. CONCLUSIONS: H2S may help to accelerate the recovery of renal function post-obstruction and attenuates renal injury associated with UUO. It is possible that H2S mitigates fibrosis by regulating the TGF-ß1-mediated EMT pathway. Taken together, our data suggest that H2S may be a potential novel therapy for improving renal function and limiting renal injury associated with obstructive uropathy.

Stones in special situations.

There are several special situations in which urinary lithiasis presents management challenges to the urologist. An in-depth knowledge of the pathophysiology, unique anatomy, and treatment options is crucial in order to maintain good health in these patients. In this review, we summarize the current literature on the management of the following scenarios: bladder stones, stones in bowel disease, during pregnancy, in association with renal anomalies, with skeletal deformities, in urinary diversions, and in children.

Surgical Management of Stones: American Urological Association/Endourological Society Guideline, PART II.

PURPOSE: This Guideline is intended to provide a clinical framework for the surgical management of patients with kidney and/or ureteral stones. The summary presented herein represents Part II of the two-part series dedicated to Surgical Management of Stones: American Urological Association/Endourological Society Guideline. Please refer to Part I for introductory information and a discussion of pre-operative imaging and special cases. MATERIALS AND METHODS: A systematic review of the literature (search dates 1/1/1985 to 5/31/2015) was conducted to identify peer-reviewed studies relevant to the surgical management of stones. The review yielded an evidence base of 1,911 articles after application of inclusion/exclusion criteria. These publications were used to create the Guideline statements. Evidence-based statements of Strong, Moderate, or Conditional Recommendation were developed based on benefits and risks/burdens to patients. Additional directives are provided as Clinical Principles and Expert Opinions when insufficient evidence existed. RESULTS: The Panel identified 12 adult Index Patients to represent the most common cases seen in clinical practice. Three additional Index Patients were also created to describe the more commonly encountered special cases, including pediatric and pregnant patients. With these patients in mind, Guideline statements were developed to aid the clinician in identifying optimal management. CONCLUSIONS: Proper treatment selection, which is directed by patient- and stone-specific factors, remains the greatest predictor of successful treatment outcomes. This Guideline is intended for use in conjunction with the individual patient's treatment goals. In all cases, patient preferences and personal goals should be considered when choosing a management strategy.

Surgical Management of Stones: American Urological Association/Endourological Society Guideline, PART I.

PURPOSE: This Guideline is intended to provide a clinical framework for the surgical management of patients with kidney and/or ureteral stones. The summary presented herein represents Part I of the two-part series dedicated to Surgical Management of Stones: American Urological Association/Endourological Society Guideline. Please refer to Part II for an in-depth discussion of patients presenting with ureteral or renal stones. MATERIALS AND METHODS: A systematic review of the literature (search dates 1/1/1985 to 5/31/2015) was conducted to identify peer-reviewed studies relevant to the surgical management of stones. The review yielded an evidence base of 1,911 articles after application of inclusion/exclusion criteria. These publications were used to create the Guideline statements. Evidence-based statements of Strong, Moderate, or Conditional Recommendation were developed based on benefits and risks/burdens to patients. Additional directives are provided as Clinical Principles and Expert Opinions when insufficient evidence existed. RESULTS: The Panel identified 12 adult Index Patients to represent the most common cases seen in clinical practice. Three additional Index Patients were also created to describe pediatric and pregnant patients with such stones. With these patients in mind, Guideline statements were developed to aid the clinician in identifying optimal management. CONCLUSIONS: Proper treatment selection, which is directed by patient- and stone-specific factors, remains the greatest predictor of successful treatment outcomes. This Guideline is intended for use in conjunction with the individual patient's treatment goals. In all cases, patient preferences and personal goals should be considered when choosing a management strategy.

Risk Factors for Postoperative Complications of Percutaneous Nephrolithotomy at a Tertiary Referral Center.

PURPOSE: We sought to describe and evaluate the complications related to percutaneous nephrolithotomy and identify risk factors of morbidity according to the modified Clavien scoring system. We also sought to specify which perioperative factors are associated with minor and major complications. MATERIALS AND METHODS: We retrospectively analyzed data on patients who underwent percutaneous nephrolithotomy from 1990 to 2013. Descriptive statistics were used to analyze patient characteristics, medical comorbidities and perioperative features. Complications were categorized according to the Clavien score for percutaneous nephrolithotomy. The Mann-Whitney and Fisher exact tests were used as appropriate. Logistic regression analysis was performed to look for prognostic factors associated with major complications. RESULTS: A total of 2,318 surgeries were evaluated. Mean age of the population was 53.7 years. The stone-free rate at hospital discharge was 81.6%. The overall complication rate was 18.3%. Two deaths occurred. Patients with any postoperative complications were older, had more comorbidities, were more likely to have staghorn calculi and had longer operative time and hospital stay on univariate analysis (p<0.05). Age 55 years or older and upper pole access were independent predictors of major complications on multivariate analysis. Other factors such as a history of urinary tract infections, body mass index, stone composition, previous percutaneous nephrolithotomy and multiple tracts were not associated with a major complication. CONCLUSIONS: At our center percutaneous nephrolithotomy is an excellent option for complex kidney stone management with a low overall complication rate. Older patient age and upper pole access are significantly associated with an increased risk of a major complication.

Clinical Research Office of the Endourological Society Global GreenLight Laser Study: Outcomes from a contemporary series of 713 patients.

OBJECTIVE: To evaluate the outcome in patients undergoing photoselective vaporization of the prostate for benign prostatic obstruction as part of the Clinical Research Office of the Endourological Society Global GreenLight Laser Study. METHODS: Data were collected on 713 patients with lower urinary tract symptoms suggestive of benign prostatic obstruction undergoing photoselective vaporization of the prostate at 25 centers worldwide, between April 2010 and April 2012. Three types of GreenLight laser powers were used: 80 W, 120 W or 180 W. Intraoperative and postoperative complications were recorded. Outcome parameters measured at baseline, 6-12 weeks, 6 months and 12 months were: uroflow measurements, International Prostate Symptom Score; prostate-specific antigen and International Index of Erectile Function. RESULTS: Operating time was shortest with the 180-W laser at 53.8 min. Intraoperatively, bleeding occurred in 3.1% of patients. Statistically significant changes were reported in maximum flow rate, postvoid residual urine, International Prostate Symptom Score, quality of life score and prostate-specific antigen (P < 0.01) at each time-point assessed for the 80- and 120-W lasers as well as for the 180-W laser, with the exception of prostate-specific antigen at 6 months and 12 months. There were 14 Clavien-Dindo grade III-A complications and two grade III-B. The incontinence rate at 12 months was 6.3%, 4.5%, and 2.6% for the 80, 120 and 180 W lasers, respectively. The overall blood transfusion rate was 0.4%. CONCLUSIONS: Objective and subjective improvement after GreenLight laser treatment worldwide was significant at 1-year follow up. Morbidity and complications were low. Although not a randomized control study, the data can provide an indication of the outcome of the different GreenLight laser powers.

Selective target inactivation rather than global metabolic dormancy causes antibiotic tolerance in uropathogens.

Persister cells represent a multidrug-tolerant (MDT), physiologically distinct subpopulation of bacteria. The ability of these organisms to survive lethal antibiotic doses raises concern over their potential role in chronic disease, such as recurrent urinary tract infection (RUTI). Persistence is believed to be conveyed through global metabolic dormancy, which yields organisms unresponsive to external stimuli. However, recent studies have contested this stance. Here, various antibiotics that target different cellular processes were used to dissect the activity of transcription, translation, and peptidoglycan turnover in persister cells. Differential susceptibility patterns were found in type I and type II persisters, and responses differed between Staphylococcus saprophyticus and Escherichia coli uropathogens. Further, SOS-deficient strains were sensitized to ciprofloxacin, suggesting DNA gyrase activity in persisters and indicating the importance of active DNA repair systems for ciprofloxacin tolerance. These results indicate that global dormancy per se cannot sufficiently account for antibiotic tolerance. Rather, the activity of individual cellular processes dictates multidrug tolerance in an antibiotic-specific fashion. Furthermore, the susceptibility patterns of persisters depended on their mechanisms of onset, with subinhibitory antibiotic pretreatments selectively shutting down cognate targets and increasing the persister fraction against the same agent. Interestingly, antibiotics targeting transcription and translation enhanced persistence against multiple agents indirectly related to these processes. Conducting these assays with uropathogenic E. coli isolated from RUTI patients revealed an enriched persister fraction compared to organisms cleared with standard antibiotic therapy. This finding suggests that persister traits are either selected for during prolonged antibiotic treatment or initially contribute to therapy failure.

Allopurinol hypersensitivity syndrome Raising awareness of an uncommon but potentially serious adverse event among kidney stone patients.

Allopurinol is a commonly prescribed agent in the urologic population for the prevention of urinary stones. Although generally well-tolerated, several serious potential side effects can occur with its use. Allopurinol hypersensitivity syndrome (AHS), in particular, is a relatively rare but potentially life-threatening complication. With the observed increase in urinary stone disease, especially those of uric acid composition, it is likely that the use of allopurinol will increase. Urologists play an important role in the assessment and medical management of patients with urinary stones, thus a greater awareness of the potential adverse events associated with allopurinol use, especially AHS, is important, as well as strategies that can minimize such risks. Herein, we review the potential adverse effects of allopurinol. In addition, the results of a comprehensive review of the current literature on AHS will be presented, highlighting those patients at highest risk, reviewing the genetic susceptibility testing currently available, and providing guidance on best practices when allopurinol therapy is being considered.

Predictive modelling of urinary stone composition using machine learning and clinical data: implications for treatment strategies and pathophysiological insights.

PURPOSE: Preventative strategies and surgical treatment for urolithiasis depend on stone composition. However, stone composition is often unknown until the stone is passed or surgically managed. Given that stone composition likely reflects the physiological parameters during its formation, we used clinical data from stone formers to predict stone composition. MATERIAL AND METHODS: Stone composition, 24-hour urine, serum biochemistry, patient demographic and medical history were prospectively collected from 777 kidney stone patients. Data were used to train gradient boosted machine and logistic regression models to distinguish calcium vs non-calcium, calcium oxalate monohydrate vs dihydrate, and calcium oxalate vs calcium phosphate vs uric acid stone types. Model performance was evaluated using kappa score and the influence of each predictor variable was assessed. RESULTS: The calcium vs non-calcium model successfully differentiated stone types with a kappa of 0.5231. The most influential predictors were 24-hour urine calcium, blood urate and phosphate. The calcium oxalate monohydrate vs dihydrate model is the first of its kind and could discriminate stone types with a kappa of 0.2042. The key predictors were 24-hour urine urea, calcium, and oxalate. The multiclass model had a kappa of 0.3023 and the top predictors were age, and 24-hour urine calcium and creatinine. CONCLUSIONS: Clinical data can be leveraged with machine learning algorithms to predict stone composition, which may help urologists determine stone type and guide their management plan before stone treatment. Investigating the most influential predictors of each classifier may improve the understanding of key clinical features of urolithiasis and shed light on the pathophysiology.

The Role of Urinary Modulators in the Development of Infectious Kidney Stones.

Introduction: The pathogenesis of infectious kidney stones is poorly understood. Bacteria have been implicated in promoting infectious stones via urease production; however, there is mounting evidence indicating the relationship is more complex. The aim of our study was to characterize suspected biotic and abiotic extrinsic factors that may modulate the formation of infectious stones. Materials and Methods: A high-throughput experimental model with Griffith's artificial urine was used to test a wide variety of urinary modulators and cytoplasmic enzymes present in crude cell-free extracts (CFEs) from bacterial strains to investigate how they impact struvite and calcium (Ca) phosphate crystal production. Crystal formation was evaluated with spectrophotometry and growth curve analysis. Light microscopy and scanning electron microscopy/X-ray diffraction was used for crystal structure and composition identification. Results: The acidic urinary modulators used in this study prevented crystal formation, whereas osteopontin had a significant inhibitory effect. Addition of CFEs from Proteus mirabilis 175A and 177A resulted in Ca phosphate and struvite crystals. Of interest, Klebsiella pneumoniae and Klebsiella oxytoca produced crystals including Ca phosphate and Ca oxalate, respectively. Pseudomonas aeruginosa had no urease production detected and produced Ca phosphate crystals. Discussion: Urinary modulators can have a wide variety of effects on infectious stone formation and the role of pH is important but does not guarantee robust crystal formation. Bacterial strains can produce Ca oxalate, Ca phosphate, and struvite stones with and without urease activity. Conclusion: Various urinary modulators appear to influence the process and are worthy of further evaluation as a potential therapeutic strategy to prevent infection-related urinary stone formation. Stones formed from urinary tract infections may be a result of multiple encoded metabolic pathways and discovering these would improve our understanding of the stone-bacterial relationship.

Vitamins as regulators of calcium-containing kidney stones - new perspectives on the role of the gut microbiome.

Calcium-based kidney stone disease is a highly prevalent and morbid condition, with an often complicated and multifactorial aetiology. An abundance of research on the role of specific vitamins (B6, C and D) in stone formation exists, but no consensus has been reached on how these vitamins influence stone disease. As a consequence of emerging research on the role of the gut microbiota in urolithiasis, previous notions on the contribution of these vitamins to urolithiasis are being reconsidered in the field, and investigation into previously overlooked vitamins (A, E and K) was expanded. Understanding how the microbiota influences host vitamin regulation could help to determine the role of vitamins in stone disease.

A population-based retrospective cohort study of surgical trends and outcomes of pediatric urolithiasis in Ontario, Canada (2002-2019).

INTRODUCTION: The worldwide incidence of pediatric urinary stone disease (PUSD) is increasing. However, there is no commensurate data on whether this translates to an increasing need for surgical intervention for PUSD, given the role of conservative management. OBJECTIVE: We aimed to evaluate the trends and outcomes of clinically significant PUSD, using administrative databases to identify patients surgically treated for PUSD. STUDY DESIGN: This retrospective population-based cohort study assessed the incidence and trends of surgically treated PUSD and outcomes in Ontario, Canada in patients <18 years of age who underwent their first PUSD procedure between 2002 and 2019 utilizing administrative databases held at the Institute of Clinical Evaluative Sciences (ICES). We assessed the incidence of surgically treated PUSD, demographics, initial surgical treatment and imaging modality, and risk factors for repeat intervention within 5 years. Statistical analyses summarized demographics, surgical trends, and logistic regression was used to identify risk factors for repeat surgical intervention. RESULTS: We identified 1149 patients (mean age 11.3 years), with 59.6% older than 12 years. There was a decrease in the number of PUSD procedures performed per year that was close to statistical significance (p = 0.059) and a trend towards increased utilization of ureteroscopy (URS) compared with Shockwave Lithotripsy (SWL). In addition, there was a significant increase in the proportion of females surgically treated with PUSD (p = 0.001). In the 706 patients followed for 5 years, 17.7% underwent a repeat procedure within 6 months, while 20.4% underwent a repeat procedure from 6-months to 5 years. Renal stone location (OR 2.79, 95% confidence interval (CI) 1.62-4.80, p = 0.0002) and index SWL (OR 1.66, 95% CI 1.20-2.31, p = 0.0025) were risk factors for repeat surgical intervention within the first 6-months. There was an increasing utilization of ultrasound (US) compared to computerized tomography (CT) (p = 0.0008). DISCUSSION: Despite the literature reporting increasing PUSD incidence, we observed a non-significant decrease in the number of surgical PUSD procedures performed. Exclusion of those treated conservatively may explain our results. The increase in the proportion of females treated reflects the narrowing gender gap in stone disease. A trend towards increased URS utilization was observed and re-intervention rates were similar to previous studies. CONCLUSION: The overall rate of surgically treated PUSD did not show an increasing trend in Ontario, Canada from 2002 to 2019. URS was the most common surgical treatment modality, with a corresponding decline in SWL rates. PUSD was associated with a high surgical re-intervention rate within 6 months.

Multi-site microbiota alteration is a hallmark of kidney stone formation.

BACKGROUND: Inquiry of microbiota involvement in kidney stone disease (KSD) has largely focussed on potential oxalate handling abilities by gut bacteria and the increased association with antibiotic exposure. By systematically comparing the gut, urinary, and oral microbiota of 83 stone formers (SF) and 30 healthy controls (HC), we provide a unified assessment of the bacterial contribution to KSD. RESULTS: Amplicon and shotgun metagenomic sequencing approaches were consistent in identifying multi-site microbiota disturbances in SF relative to HC. Biomarker taxa, reduced taxonomic and functional diversity, functional replacement of core bioenergetic pathways with virulence-associated gene markers, and community network collapse defined SF, but differences between cohorts did not extend to oxalate metabolism. CONCLUSIONS: We conclude that multi-site microbiota alteration is a hallmark of SF, and KSD treatment should consider microbial functional restoration and the avoidance of aberrant modulators such as poor diet and antibiotics where applicable to prevent stone recurrence. Video Abstract.

Corrigendum: New perspectives on an old grouping: the genomic and phenotypic variability of Oxalobacter formigenes and the implications for calcium oxalate stone prevention.

[This corrects the article DOI: 10.3389/fmicb.2022.1011102.].

In focus: perplexing increase of urinary stone disease in children, adolescent and young adult women and its economic impact.

Background: Urinary stone disease (USD) historically has affected older men, but studies suggest recent increases in women, leading to a near identical sex incidence ratio. USD incidence has doubled every 10 years, with disproportionate increases amongst children, adolescent, and young adult (AYA) women. USD stone composition in women is frequently apatite (calcium phosphate), which forms in a higher urine pH, low urinary citrate, and an abundance of urinary uric acid, while men produce more calcium oxalate stones. The reasons for this epidemiological trend are unknown. Methods: This perspective presents the extent of USD with data from a Canadian Province and a North American institution, explanations for these findings and offers potential solutions to decrease this trend. We describe the economic impact of USD. Findings: There was a significant increase of 46% in overall surgical interventions for USD in Ontario. The incidence rose from 47.0/100,000 in 2002 to 68.7/100,000 population in 2016. In a single United States institution, the overall USD annual unique patient count rose from 10,612 to 17,706 from 2015 to 2019, and the proportion of women with USD was much higher than expected. In the 10-17-year-old patients, 50.1% were girls; with 57.5% in the 18-34 age group and 53.6% in the 35-44 age group. The roles of obesity, diet, hormones, environmental factors, infections, and antibiotics, as well as the economic impact, are discussed. Interpretation: We confirm the significant increase in USD among women. We offer potential explanations for this sex disparity, including microbiological and pathophysiological aspects. We also outline innovative solutions - that may require steps beyond typical preventive and treatment recommendations.

The CROES percutaneous nephrolithotomy global study: the influence of body mass index on outcome.

PURPOSE: In addition to more commonly forming stones, obese patients present a number of challenges when undergoing percutaneous nephrolithotomy. We evaluated percutaneous nephrolithotomy outcomes in 3,709 patients stratified by body mass index. MATERIALS AND METHODS: A prospective database administered by CROES (Clinical Research Office of the Endourological Society) captured data on 5,803 patients treated with percutaneous nephrolithotomy between November 2007 and December 2009. Patients with known solitary kidney, previous percutaneous nephrolithotomy and congenital abnormalities were excluded from analysis. For statistical analysis patients were categorized as normal weight--body mass index 18.5 to 25 kg/m(2), overweight--25 to 30, obese--30 to 40 and super obese--greater than 40. RESULTS: During the study period 5,803 patients underwent percutaneous nephrolithotomy, of whom 3,709 met the inclusion criteria. As expected, obesity was associated with significantly higher rates of comorbid conditions and anticoagulant use (p < 0.001). Operative time was significantly longer in obese patients and use of a balloon device for tract dilation was more common (each p < 0.001). The stone-free rate decreased with obesity (p = 0.009), corresponding to a significantly higher re-treatment rate in this group (p < 0.001). No difference was seen in length of stay or the transfusion rate. No significant difference was seen in the overall complication rate among the 4 groups (p = 0.707). CONCLUSIONS: Percutaneous nephrolithotomy may be done safely in obese patients, although with a longer operative time, an inferior stone-free rate and a higher re-intervention rate.