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Purpose: To ensure that research on kidney stones provides meaningful impact for the kidney stone community, patients and caregivers should be engaged as stakeholders in clinical trial design, starting at study inception. This project aimed to elicit, refine, and prioritize research ideas from kidney stone stakeholders to develop a patient-centered research agenda for clinical trials., Materials and Methods: The Kidney Stone Engagement Core, a group of patients, caregivers, advocates, clinicians, and researchers, executed an iterative process of surveys and focus groups to elicit and refine research themes, which were then translated into research questions. A separate group of patients, caregivers, and clinicians prioritized these questions through parallel modified Delphi and crowd-sourced digital platforms. A research agenda was developed by the Kidney Stone Engagement Core based on the highest rated questions during a hybrid virtual/in-person capstone session., Results: A total of 70 individuals (57 patients and caregivers, 13 researchers and clinicians) participated in the elicitation, 20 individuals (15 patients and caregivers, 5 researchers and clinicians) participated in refinement, and an additional 80 individuals (81 patients and caregivers, 9 researchers and clinicians) participated in prioritization. Key novel themes emerged from elicitation and refinement: ureteral stents, genetic evaluation, shared surgical decision-making, key subgroups, cumulative disease burden, genetic evaluation, and psychosocial support. Stakeholders generated 6 proposed trials from these themes focused on surveillance, surgical intervention, and medical prevention., Conclusions: Patients and caregivers valued comparative effectiveness kidney stone research that focused on individualized care, shared decision-making, and improvement of patient-reported experiences. This process provided actionable recommendations for future patient-centered clinical trials within kidney stone disease.

Ethnopharmacological Relevance: The leaves of Quercus dentata Thunb. (QD), a member of the Fagaceae family and genus Quercus, with distributions in China, Japan, Korea, and other regions. As recorded in the Ben Cao Gang Mu (Compendium of Materia Medica) and other classical Chinese medical texts, QD has been traditionally employed in Traditional Chinese Medicine (TCM) for their hemostatic and diuretic effects and has been used to treat urinary stones (Lin Zheng). It is also the main ingredient of the Mishitong capsule (MST), a Chinese patent drug, used for kidney stones and ureteral stones. Nonetheless, the specific active ingredients and the mechanisms of QD in treating kidney stones remain to be elucidated, which is crucial for advancing the scientific understanding and clinical application of this traditional medicine., Aim of Study: This study aimed to identify the active constituents of QD water extract (QDWE), explore its inhibitory effects on kidney stones through in vitro and in vivo studies, and elucidate the underlying mechanisms of the OPN/CD44 axis and the NLRP3 signaling pathway to provide a full understanding of its potential as a novel treatment approach against kidney stones., Materials and Methods: The micromolecular components in the supernatant of QDWE (QDS) were analyzed by UPLC-Q-Exactive-Orbitrap-MS and the monosaccharide composition of the macromolecular polysaccharide components in the crude polysaccharide (QDP) was determined by pre-column derivatization in HPLC. The effects of QDWE, QDS and QDP on the shape, size, and structure of calcium oxalate (CaOx) crystals in vitro were explored by XRD, FTIR and SEM. The effects of QDWE, QDS and QDP on CaOx kidney stones in SD rats induced by ethylene glycol and VD 3 were compared in vivo. Furthermore, the underlying mechanisms of OPN/CD44 and NLRP3 pathways were investigated by Western blot analysis., Results: There were 32 compounds identified in QDS. The monosaccharide composition ratio of QDP was Man: L-Rha: D-GlcA: D-GalA: D-Glc: D-Gal: L-Ara = 1.01: 22.52: 8.27: 38.61: 3.43: 17.80: 6.38, indicating a mixture of pectin-type acidic heteropolysaccharides. QDP had a more significant inhibitory effect on CaOx crystals in vitro than QDWE, which can inhibit the formation of CaOx monohydrate crystals (COM) and convert them into thermodynamically unstable CaOx dihydrate (COD) crystals. The high dose of QDWE exhibited significant in vivo efficacy (P<0.05), including anti-calculus, diuretic effects, and kidney protection, marked by decreased calcification and stone formation, alongside improved kidney vitality. Furthermore, the protective effects of QDWE were demonstrated to be associated with the OPN/CD44 and NLRP3 pathways., Conclusion: The studies identified and analyzed the active constituents of QDWE. Among these, QDP significantly inhibited CaOx crystal generation in vitro and could be a potential component for the treatment of urinary stones in QDWE. Moreover, the results indicated that QDWE had a remarkable therapeutic effect on CaOx stones by modulating the OPN/CD44 axis to affect stone formation and the NLRP3 signaling pathway to mediate inflammation, providing an experimental basis for the mechanism of anti-urinary stone and deep development of QD., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Calcium (Ca2+) is an essential divalent cation involved in many bodily functions including bone composition, cell growth and division, blood clotting, and muscle contraction. The bone, intestine, and kidneys are important to the maintenance of Ca2+ homeostasis. Ninety-nine percent of body Ca2+ is stored in the skeleton as hydroxyapatite. The small, and to a lesser extent the large intestine absorbs Ca2+ from the diet. Once in the circulation, Ca2+ is filtered by the glomerulus and the majority, >95%, is reabsorbed along the nephron. The remainder is excreted in the urine. Two general (re)absorptive pathways contribute to the vectorial transport of Ca2+ across renal and intestinal epithelia: 1) a paracellular pathway, which is reliant on claudins in the tight junction of epithelium and the electrochemical gradient and 2) a transcellular pathway, which requires different influx, intracellular buffering/shuttling and basolateral efflux mechanisms, to actively transport Ca2+ across the epithelial cell. Blood Ca2+ levels are maintained by hormones including parathyroid hormone, 1,25-dihydroxyvitamin D3, fibroblast growth factor 23 and through effects of Ca2+-sensing receptor (CaSR) signaling. Disruption of Ca2+ homeostasis can result in altered blood Ca2+ levels and/or hypercalciuria, the latter is a phenomenon closely linked to the formation of kidney stones. Genetic alterations affecting renal Ca2+ handling can cause hypercalciuria, an area of expanding investigation. This review explores the molecular mechanisms governing Ca2+ homeostasis by the intestine and kidneys and discusses clinical aspects of genetic disorders associated with Ca2+-based kidney stone disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Kidney Stone Disease (KSD) constitutes a multifaceted disorder, emerging from a confluence of environmental and genetic determinants, and is characterized by a high frequency of occurrence and recurrence. Our objective is to elucidate potential causative proteins and identify prospective pharmacological targets within the context of KSD. This investigation harnessed the unparalleled breadth of plasma protein and KSD pooled genome-wide association study (GWAS) data, sourced from the United Kingdom Biobank Pharma Proteomics Project (UKBPPP) and the FinnGen database version R10. Through Mendelian randomization analysis, proteins exhibiting a causal influence on KSD were pinpointed. Subsequent co-localization analyses affirmed the stability of these findings, while enrichment analyses evaluated their potential for pharmacological intervention. Culminating the study, a phenome-wide association study (PheWAS) was executed, encompassing all phenotypes (2408 phenotypes) catalogued in the FinnGen database version R10. Our MR analysis identified a significant association between elevated plasma levels of proteins FKBPL, ITIH3, and SERPINC1 and increased risk of KSD based on genetic predictors. Conversely, proteins CACYBP, DAG1, ITIH1, and SEMA6C showed a protective effect against KSD, documented with statistical significance (P FDR <0.05). Co-localization analysis confirmed these seven proteins share genetic variants with KSD, signaling a shared genetic basis (PPH3 + PPH4 > 0.8). Enrichment analysis revealed key pathways including hyaluronan metabolism, collagen-rich extracellular matrix, and serine-type endopeptidase inhibition. Additionally, our PheWAS connected the associated proteins with 356 distinct diseases (P FDR <0.05), highlighting intricate disease interrelations. In conclusion, our research elucidated a causal nexus between seven plasma proteins and KSD, enriching our grasp of prospective therapeutic targets., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate and compare the quality and comprehensibility of answers produced by five distinct artificial intelligence (AI) chatbots-GPT-4, Claude, Mistral, Google PaLM, and Grok-in response to the most frequently searched questions about kidney stones (KS). Materials and Methods: Google Trends facilitated the identification of pertinent terms related to KS. Each AI chatbot was provided with a unique sequence of 25 commonly searched phrases as input. The responses were assessed using DISCERN, the Patient Education Materials Assessment Tool for Printable Materials (PEMAT-P), the Flesch-Kincaid Grade Level (FKGL), and the Flesch-Kincaid Reading Ease (FKRE) criteria. Results: The three most frequently searched terms were "stone in kidney," "kidney stone pain," and "kidney pain." Nepal, India, and Trinidad and Tobago were the countries that performed the most searches in KS. None of the AI chatbots attained the requisite level of comprehensibility. Grok demonstrated the highest FKRE (55.6 ± 7.1) and lowest FKGL (10.0 ± 1.1) ratings ( p = 0.001), whereas Claude outperformed the other chatbots in its DISCERN scores (47.6 ± 1.2) ( p = 0.001). PEMAT-P understandability was the lowest in GPT-4 (53.2 ± 2.0), and actionability was the highest in Claude (61.8 ± 3.5) ( p = 0.001). Conclusion: GPT-4 had the most complex language structure of the five chatbots, making it the most difficult to read and comprehend, whereas Grok was the simplest. Claude had the best KS text quality. Chatbot technology can improve healthcare material and make it easier to grasp.

The association of alcohol intake with kidney stone disease (KSD) is not clear based on current clinical evidence. We examined the National Health and Nutrition Examination Survey (NHANES) 2007-2018 and used logistic regression analyses to determine the independent association between alcohol intake and prevalent KSD. In total, 29,684 participants were eligible for the final analysis, including 2840 prevalent stone formers (SFs). The mean alcohol intake was 37.0 ± 2.4 g/day among SFs compared to 42.7 ± 0.9 among non-SFs ( p = 0.04). Beer [odds ratio (OR) = 0.76, 95% CI: 0.61-0.94, p = 0.01] and wine (OR = 0.75, 95% CI: 0.59-0.96, p = 0.03) intakes were strongly associated with lower odds of prevalent KSD, while liquor intake had no association. Furthermore, the effects of beer and wine intakes on stone formation were dose-dependent. The OR for comparing participants drinking 1-14 g/day of beer to non-drinkers was 1.41 (95%CI: 0.97-2.05, p = 0.07), that of >14-≤28 g/day of beer to non-drinkers was 0.65 (95% CI: 0.42-1.00, p = 0.05), that of >28-≤56 g/day of beer to non-drinkers was 0.60 (95% CI: 0.39-0.93, p = 0.02), and that of >56 g/day of beer to non-drinkers was 0.34 (95% CI: 0.20-0.57, p < 0.001). Interestingly, the effect of wine intake was only significant among participants drinking moderate amounts (>14-28 g/day), with an OR of 0.54 (95% CI: 0.36-0.81, p = 0.003) compared to non-drinkers, but this effect was lost when comparing low-level (1-14 g/day) and heavy (>28 g/day) wine drinkers to non-drinkers. These effects were consistent in spline models. This study suggests that both moderate to heavy beer intake and moderate wine intake are associated with a reduced risk of KSD. Future prospective studies are needed to clarify the causal relationship.

Background: At present, few articles on percutaneous nephrolithotomy (PCNL) for renal calculi and renal pelvic tumors detected by intraoperative biopsy exist, which has provided limited guidance for clinical practice. In this article, we aimed to further study the relationship between renal calculi and renal pelvic tumors., Methods: We retrospectively analyzed the medical records of patients with abnormal mucosal biopsy results who underwent PCNL for kidney stones in the Urology Department of Peking University People's Hospital from January 2011 to November 2021., Results: In total, 2,801 patients underwent PCNL for kidney stones, of whom 69 underwent intraoperative mucosal biopsy. Biopsy results indicated that 8 cases were malignant (11.60%), and 61 cases were benign (88.40%). All malignant cases were renal pelvic carcinoma. Seven were urothelial carcinoma, and one of these was urothelial carcinoma with squamous differentiation. Only one was squamous cell carcinoma. The preoperative information of patients with a malignant mucosa biopsy was analyzed. To provide clinical guidance, an early warning biopsy system was established based on the abnormal mucosa found during the operation. We found that PCNL should be considered if the following risk factors are associated with stones: advanced age, long history of kidney stones, severe hydronephrosis, urinary tract infection, multiple or staghorn stones., Conclusions: Early warning information should be established for patients with kidney stones based on preoperative clinical characteristics and intraoperative mucous membrane observations. An early warning biopsy should be performed for patients with possible tumors to detect tumors in a timely manner and provide early treatment to improve patient prognosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-91/coif). The authors have no conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.)

A 39-year-old man was admitted to our hospital with kidney stones after kidney transplantation. Kidney, ureter, and bladder radiographs showed multiple stones in the transplanted and orthotopic kidneys, which had not been reported previously. Owing to the larger size of the stones in the transplanted kidney, they needed to be removed. Percutaneous nephrolithotomy and ureteroscopy were performed under B-mode ultrasound guidance. The stone measured 1.9 × 1.6 cm and was located under the calyx of the kidney. A titanium laser fiber was used to dissolve the stones, which were subsequently removed. No adverse reactions occurred during or after the surgery. The causes of stone formation included dietary factors, related drugs, improper fluid intake, and urinary tract infections. As neither the donor nor the recipient had a history of kidney stones, we hypothesized that the stones were a new entity that either developed following transplantation or a long-term complication., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Calcium-containing stones represent the most common form of kidney calculi, frequently linked to idiopathic hypercalciuria, though their precise pathogenesis remains elusive. This research aimed to elucidate the molecular mechanisms involved by employing urinary exosomal microRNAs as proxies for renal tissue analysis. Elevated miR-148b-5p levels were observed in exosomes derived from patients with kidney stones. Systemic administration of miR-148b-5p in rat models resulted in heightened urinary calcium excretion, whereas its inhibition reduced stone formation. RNA immunoprecipitation combined with deep sequencing identified miR-148b-5p as a suppressor of calcitonin receptor (Calcr) expression, thereby promoting urinary calcium excretion and stone formation. Mice deficient in Calcr in distal epithelial cells demonstrated elevated urinary calcium excretion and renal calcification. Mechanistically, miR-148b-5p regulated Calcr through the circRNA-83536/miR-24-3p signaling pathway. Human kidney tissue samples corroborated these results. In summary, miR-148b-5p regulates the formation of calcium-containing kidney stones via the circRNA-83536/miR-24-3p/Calcr axis, presenting a potential target for novel therapeutic interventions to prevent calcium nephrolithiasis., (© 2024. The Author(s).)

Introduction: Percutaneous nephrolithotomy (PCNL) is a common procedure for kidney stone removal, involving a small incision in the back and insertion of a nephroscope to extract the stones. Recent advancements include super-mini PCNL, employing smaller instruments for less invasive access to the kidney. However, conventional PCNL often requires tract dilation, which can lead to potential complications., Case Presentation: This case report presents the successful application of our surgical technique using the basic principles of PCNL with the aid of a pediatric trocar cystostomy and ultrasound guidance as a new alternative for super-mini PCNL, offering safer access with reduced bleeding risk and shorter recovery. The surgery was performed on a 55-year-old female with bilateral kidney stones, with the stone in the left kidney being larger than the one in the right kidney. The procedure was completed within 60 min without significant postoperative complications., Discussion: Our new alternative for PCNL offers benefits such as reduced invasiveness, shorter recovery time, decreased risk of complications, and minimal changes in postoperative hemoglobin levels. This new alternative can be performed in developing country hospitals that do not have the expensive PCNL equipment., Conclusion: This new alternative of PCNL with pediatric trocar cystostomy proves to be effective and safe., Competing Interests: Conflict of interest statement The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

In today's digital world, with growing population and increasing pollution, unhealthy lifestyle habits like irregular eating, junk food consumption, and lack of exercise are becoming more common, leading to various health problems, including kidney issues. These factors directly affect human kidney health. To address this, we require early detection techniques that rely on text data. Text data contains detailed information about a patient's medical history, symptoms, test results, and treatment plans, giving a complete picture of kidney health and enabling timely intervention. In this research paper, we proposed a range of sophisticated models, such as Gradient Boosting Classifier, Light GBM, CatBoost, Support Vector Classifier (SVC), Random Boost, Logistic Regression, XGBoost, Deep Neural Network (DNN), and an Improved DNN. The Improved DNN demonstrated exceptional performance, with an accuracy of 90 %, precision of 89 %, recall of 90 %, and an F1-Score of 89.5 %. By combining traditional machine learning and deep neural networks, this integrative approach enables the identification of intricate patterns in datasets. The model's data-driven processes consistently update internal parameters, guaranteeing flexibility in response to evolving healthcare settings. This research represents a notable advancement in the progress of creating a more detailed and individualised ability to diagnose kidney stones, which could potentially lead to better clinical results and patient treatment., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Recent evidence has shown that proteins in normal human urine can inhibit calcium oxalate (CaOx) kidney stone formation. Herein, we performed fast protein liquid chromatography (FPLC) to fractionate normal human urinary proteins using anion-exchange (DEAE) and size-exclusion (Superdex 200) materials. FPLC fractions (F1-F15) were examined by CaOx crystallization, growth, aggregation and crystal-cell adhesion assays. The fractions with potent inhibitory activities against CaOx crystals were then subjected to mass spectrometric protein identification. The data revealed that 13 of 15 fractions showed inhibitory activities in at least one crystal assay. Integrating CaOx inhibitory scores demonstrated that F6, F7 and F8 had the most potent inhibitory activities. NanoLC-ESI-Qq-TOF MS/MS identified 105, 93 and 53 proteins in F6, F7 and F8, respectively. Among them, 60 were found in at least two fractions and/or listed among known inhibitors with solid experimental evidence in the StoneMod database (https://www.stonemod.org). Interestingly, 10 of these 60 potential inhibitors have been reported with lower urinary levels in CaOx stone formers compared with healthy (non-stone) individuals, strengthening their roles as potent CaOx stone inhibitors. Our study provides the largest dataset of potential CaOx stone inhibitory proteins that will be useful for further elucidations of stone-forming mechanisms and ultimately for therapeutic/preventive applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: The absence of predictive markers for kidney stone recurrence poses a challenge for the clinical management of stone disease. The unpredictability of stone events is also a significant limitation for clinical trials, where many patients must be enrolled to obtain sufficient stone events for analysis. In this study, we sought to use machine learning methods to identify a novel algorithm to predict stone recurrence. Subjects/Patients and Methods: Patients enrolled in the Registry for Stones of the Kidney and Ureter (ReSKU), a registry of nephrolithiasis patients collected between 2015-2020, with at least one prospectively collected 24-hour urine test (Litholink 24-hour urine test; Labcorp) were included in the training set. A validation set was obtained from chart review of stone patients not enrolled in ReSKU with 24-hour urine data. Stone events were defined as either an office visit where a patient reports symptomatic passage of stones or a surgical procedure for stone removal. Seven prediction classification methods were evaluated. Predictive analyses and receiver operator characteristics (ROC) curve generation were performed in R. Results: A training set of 423 kidney stone patients with stone event data and 24-hour urine samples were trained using the prediction classification methods. The highest performing prediction model was a Logistic Regression with ElasticNet machine learning model (area under curve [AUC] = 0.65). Restricting analysis to high confidence predictions significantly improved model accuracy (AUC = 0.82). The prediction model was validated on a validation set of 172 stone patients with stone event data and 24-hour urine samples. Prediction accuracy in the validation set demonstrated moderate discriminative ability (AUC = 0.64). Repeat modeling was performed with four of the highest scoring features, and ROC analyses demonstrated minimal loss in accuracy (AUC = 0.63). Conclusion: Machine-learning models based on 24-hour urine data can predict stone recurrences with a moderate degree of accuracy.

Introduction: Decision-making for complex pediatric urinary system stone disease is still a challenge for pediatric urologists. The interest in supine percutaneous nephrolithotomy (PCNL) is increasing among centers to achieve high surgical success rates with less morbidity. Despite advanced retrograde intrarenal surgery armamentarium, percutaneous approaches remain the first-line surgical treatment modality for >2 cm and complex renal stones. There are no comparative studies yet in the literature for pediatric endoscopic combined intrarenal surgery (ECIRS) OBJECTIVE: In this study, we aimed to contribute to the literature by evaluating the safety and efficacy of ECIRS by comparing it with PCNL., Study Design: Patients under 18 years of age who underwent PCNL and ECIRS for urinary tract stone disease at our Pediatric Urology department between 2012 and 2024 were included. Preoperative (demographic characteristics, stone characteristics, biochemical parameters), perioperative (duration of surgery, number of accesses, lasing and fluoroscopy times, endoscopic and fluoroscopic stone-free rates) and postoperative (hospital stay, urinary tract infection, complication and radiological stone-free rates) parameters were retrospectively evaluated., Results: A total of 68 children [28 (41%) girls and 40 (59%) boys] aged 5 (0-17) years were included in the study. ECIRS was performed in 19 (28%), supine in 28 (41%) and prone PCNL in 21 (30%) patients. Age (p = 0.029), Guy's stone score (p < 0.001), S.T.O.N.E. (p < 0.001), and Seoul National University Renal Stone Complexity (S-ReSC) scores (p = 0.001) for preoperative parameters were found to be higher in ECIRS group over both PCNL methods (Summary Table). However, Clinical Research Office of the Endourological Society (CROES) score was seen lower for ECIRS group patients compared to other groups (p = 0.028). Surgery time (in favor of supine over prone PCNL), fluoroscopy time (in favor of ECIRS and Supine PCNL over Prone PCNL), preferred laser type (prone PCNL group was mostly performed with holmium laser, whereas other groups were balanced between Holmium and Thulium Fiber Laser) and exit strategy (the preferred exit strategy was DJ Stent in most of the ECIRS patients, whereas nephrostomy tube was used in some of the PCNL group) showed significant difference among the groups as perioperative parameters (p = 0.042, <0.001, <0.001, <0.001, respectively). Surgery time was lower for supine PCNL compared to prone PCNL. For postoperative parameters, stone-free rates, complication rates and urinary tract infections were similar between the 3 groups, while a difference was detected in terms of length of hospital stay in favor of ECIRS over both supine and prone PCNL (p = 0.006)., Discussion: The current trial suggests that stone-free and complication rates of ECIRS and supine PCNL were similar in the pediatric complex stone patients. Although, the stones in the ECIRS group we found to be more complex. Also, ECIRS was superior to PCNL in terms of fluoroscopy exposure and hospital stay., Conclusion: With the widespread use of new generation ureteral access sheaths and flexible ureterorenoscopes, ECIRS may have an important role in treatment of complex pediatric kidney stones., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Genetic variability persists across diverse populations, and it may impact the characterization of heritable diseases in different ancestral groups. Cystinosis is a metabolic disease caused by pathogenic variants in the CTNS gene causing the cellular accumulation of cystine. We attempted to assess the currently poorly characterized prevalence of cystinosis by employing a population genetics methodology. However, we encountered a significant challenge due to genetic variations across different populations, and the consideration of potential disparities in access to healthcare made our results inconclusive. Pathogenic CTNS variants were identified in a representative global population cohort using The Human Gene Mutation Database (HGMD) and the 1000 Genomes (1 KG) database. The c.124G>A (p.Val42Ile) variant was reported to be pathogenic based on an observation in the white population presenting with atypical phenotypes, but it would be reclassified as benign in the African ancestral group if applying the ACMG allele frequency guideline due to its high allele frequency specifically in this population. Inclusion or exclusion of this c.124G>A (p.Val42Ile) variant results in a significant change in estimated disease prevalence, which can impact the diagnosis and treatment of affected patients with a broad range of phenotypic presentations. This observation led us to postulate that pathogenic manifestations of the disease may be underdiagnosed due to variable expressivity and systemic inequities in access to care, specifically in the African subpopulation. We call for a more cautious and inclusive approach to achieve more equitable care across diverse populations., Competing Interests: C-HW serves as the Executive Committee of the Harrington Scholar-Innovator Award Program. C-HW is also conducting clinical trials with Moderna. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Tomaszewski, Stark, Scaglia, Elenberg and Schumaker.)

Purpose: This ex vivo study aimed to compare a newly developed dual-source photon-counting CT (PCCT) with a 3rd generation dual-source dual-energy CT (DECT) for the detection and measurement (stone lengths and volumetrics) of urinary stones., Methods: 143 urinary stones with a known geometry were physically measured and defined as reference values. Next, urinary stones were placed in an anthropomorphic abdomen-model and were scanned with DECT and PCCT. Images were read by two experienced examiners and automatically evaluated using a specific software., Results: DECT and PCCT showed a high sensitivity for manual stone detection of 97.9% and 94.4%, and for automatic detection of 93.0% and 87.4%, respectively. Compared to that uric acid and xanthine stones were recognized slightly worse by DECT and PCCT with manual stone detection (93.3% and 82.2%), and with automatic detection (77.8% and 60.0%). All other stone entities were completely recognized. By comparing the maximum diameter of the reference value and DECT, Pearson-correlation was 0.96 (p < 0.001) for manual and 0.97 (p < 0.001) for automatic measurement, and for PCCT it was 0.94 (p < 0.001) for manual and 0.97 (p < 0.001) for automatic measurements. DECT and PCCT can also reliably determine volume manually and automatically with a Pearson-correlation of 0.99 (p < 0.001), respectively., Conclusion: Both CTs showed comparable results in stone detection, length measurement and volumetry compared to the reference values. Automatic measurement tends to underestimate the maximum diameter. DECT proved to be slightly superior in the recognition of xanthine and uric acid stones., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Magnesium is one of the recommended treatments for calcium stone formers (CSFs) with hyperoxaluria. In this study, we compared the effect of magnesium oxide (MgO) or magnesium citrate (MgCit) with placebo on 24-hour urine (24-U) metabolites and the calcium oxalate supersaturation index (CaOx SS). In a randomized, double-blind, placebo-controlled clinical trial, 90 CSFs with idiopathic hyperoxaluria were recruited from a tertiary stone prevention clinic. Patients were randomly assigned into three groups: 120 mg MgO, 120 mg MgCit or placebo (supplements were taken three times per day, with meals). Finally, 76 patients were included in the final analysis. Analyses of 24-U were performed at baseline and after eight weeks. Study outcomes included changes in 24-U oxalate, magnesium, citrate, and CaOx SS. Dietary factors were controlled by 24-hour food recalls. Repeated measure ANOVA was used to compare the results. After the intervention, both MgO and MgCit supplements decreased 24-U oxalate excretion (-8.13±16.45 in the MgO group and -16.99±18.02 in the MgCit group) and CaOx SS compared to the placebo, with the effects of MgCit reaching statistical significance (p=0.011 and p=0.010, respectively). An increasing trend was observed for 24-U magnesium and citrate excretion without significant differences among groups. Interestingly, MgCit exhibited a significantly greater inhibitory effect on 24-U oxalate in patients with normal urine magnesium levels (p=0.021). Clinically, both MgO and MgCit reduced 24-U oxalate and CaOx SS compared to placebo. However, MgCit demonstrated a greater effect, especially in patients with normal urine magnesium levels.

Object: The association between magnesium depletion score (MDS) and kidney stone disease (KSD) remains unknown. This study was designed to investigate the association of MDS with KSD in adults., Methods: A total of 19,654 participants were enrolled from the National Health and Nutrition Examination Surveys (NHANES). The MDS was calculated by assessing four aspects, including alcohol assumption, renal function, and use of diuretics and proton pump inhibitor. Multivariable logistic regressions were performed to explore the associations between MDS and the prevalence of KSD. Linear correlations were conducted explore the relationship of testosterone with MDS., Results: In the multivariable logistic regressions with full adjustment for confounding variables, the odds ratio of MDS associating with KSD was 1.28 (95% CI: 1.04-1.58, P = 0.022) in total population, and 1.70 (95% CI: 1.16-2.50, P=0.007) in female participants. Besides, compared to the lowest MDS, the highest MDS was associated with a lower testosterone (β = -16.39, P=0.009) after full adjustment in non-menopause women., Conclusion: This study highlighted a positive correlation of high MDS with KSD in female population, which may be associated low level of serum testosterone., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Thiazide and thiazide-like diuretics (thiazides) belong to the most frequently prescribed drugs worldwide. By virtue of their natriuretic and vasodilating properties, thiazides effectively lower blood pressure and prevent adverse cardiovascular outcomes. In addition, through their unique characteristic of reducing urine calcium, thiazides are also widely employed for the prevention of kidney stone recurrence and reduction of bone fracture risk. Since their introduction into clinical medicine in the early 1960s, thiazides have been recognized for their association with metabolic side effects, particularly impaired glucose tolerance, and new-onset diabetes mellitus. Numerous hypotheses have been advanced to explain thiazide-induced glucose intolerance, yet underlying mechanisms remain poorly defined. Regrettably, the lack of understanding and unpredictability of these side effects has prompted numerous physicians to refrain from prescribing these effective, inexpensive, and widely accessible drugs. In this review, we outline the pharmacology and mechanism of action of thiazides, highlight recent advances in the understanding of thiazide-induced glucose intolerance, and provide an up-to-date discussion on the role of thiazides in kidney stone prevention., (© 2024 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Objective: To investigate the association between atherogenic index of plasma (AIP) and kidney stones (KS) occurrence and recurrence., Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2014. Non-pregnant adults who provided complete information on AIP and KS were included in the analyses. AIP was calculated as log (triglyceride/high-density lipoprotein cholesterol). KS was ascertained with questionnaires. Weighted multivariable logistic regression model and restricted cubic spline (RCS) were applied to examine the associations between AIP and KS occurrence and recurrence., Results: A total of 6488 subjects (weighted mean age 43.19 years and 49.26% male) with a weighted mean AIP of 0.66 were included in this study. The multivariable-adjusted OR for nephrolithiasis occurrence across consecutive tertiles was 1.00 (reference), 1.21 (95% CI: 0.90-1.62), and 1.85 (95% CI: 1.39-2.48), respectively. Moreover, each SD increment of AIP was associated with a 50% (OR:1.50, 95% CI: 1.25-1.81) higher risk of nephrolithiasis recurrence. RCSs showed significant and linear dose-response relationships between AIP and nephrolithiasis occurrence ( p -overall = 0.006, p -nonlinear = 0.689) and recurrence ( p -overall = 0.001, p -nonlinear = 0.848). The positive associations between AIP and nephrolithiasis occurrence and recurrence persisted in sensitivity analyses, suggesting the robustness of the results., Conclusion: In the current US nationally representative cross-sectional study, AIP was positively associated with KS occurrence and recurrence.

Oxalate-induced damage to renal tubular epithelial cells (RTECs) is an essential factor in the incident kidney stone, but the specific mechanism is unclear. Recent research has pinpointed interacting areas within the endoplasmic reticulum and mitochondria, called mitochondria-associated membranes (MAMs). These studies have linked endoplasmic reticulum stress (ERS) and oxidative imbalance to kidney disease development. The sigma-1 receptor (S1R), a specific protein found in MAMs, is involved in various physiological processes, but its role in oxalate-induced kidney stone formation remains unclear. In this study, we established cellular and rat models of oxalate-induced kidney stone formation to elucidate the S1R's effects against ERS and apoptosis and its mechanism in oxalate-induced RTEC injury. We found that oxalate downregulated S1R expression in RTECs and escalated oxidative stress and ERS, culminating in increased apoptosis. The S1R agonist dimemorfan up-regulated S1R expression and mitigated ERS and oxidative stress, thereby reducing apoptosis. This protective effect was mediated through S1R inhibition of the CHOP pathway. Animal experiments demonstrated that S1R's activation attenuated oxalate-induced kidney injury and alleviated kidney stone formation. This is the first study to establish the connection between S1R and kidney stones, suggesting S1R's protective role in inhibiting ERS-mediated apoptosis to ameliorate kidney stone formation.

Purpose: Remnant cholesterol (RC) is the cholesterol content of triglyceride-rich lipoproteins. This study aimed to investigate the association between RC levels and kidney stones in U.S. adults., Methods: Data were obtained from the 2007 to 2016 National Health and Nutrition Examination Survey (NHANES). A total of 10,551 participants with complete data were included and analyzed in this study. Univariate and multivariate logistic regression analysis, restricted cubic spline function, subgroup analysis and mediation analysis were preformed to estimate the independent relationship between RC levels and kidney stones., Results: Participants with stone formation had higher levels of RC than those with without stone formation (25.78 ± 13.83 vs 23.27 ± 13.04, p <   0.001). The results of logistic regression analysis and dose-response risk curves revealed a positive nonlinear association between RC levels and risk of kidney stones [univariate: adjusted odds ratio (aOR) =2.388, 95% CI: 1.797-3.173, p <   0.001; multivariate: aOR = 1.424, 95% CI: 1.050-1.929, p  =   0.023]. Compared with the discordantly low RC group, the discordantly high RC group was associated with increased risk of kidney stones (aOR = 1.185, 95% CI: 1.013-1.386, p =   0.034). Similar results were demonstrated according to the discordance of different clinical cut points. And metabolic syndrome parameters and vitamin D levels parallelly mediated the association between RC and kidney stone risk., Conclusions: Higher RC levels were independently associated with an increased risk of kidney stone incidence.

Background: Previous studies have linked kidney stone disease (KSD) with depression, but there are no reports on the relationship between anxiety and KSD, and the mechanism underlying the potential relationship remains unclear., Methods: Associations of anxiety and incident KSD were assessed in the National Health and Nutrition Examination Survey (NHENES) using multivariate logistic regression. Two-sample bidirectional Mendelian randomization studies and a two-step two-sample MR was used to estimate the mediating factors that influence KSD risk., Results: Examinations of NHANES data revealed that a rise in the frequency and intensity of anxiety were independently associated with incident KSD. In MR analysis, anxiety (uk-a-51 and uk-b-6519) were from the UK Biobank, with sample sizes of 328,717 and 450,765 respectively. KSD data were from the FinnGen, including 8597 cases and 333,128 controls. In the IVW analysis, genetically predicted anxieties (ukb-a-51 and ukb-b-6519) were found to be causally associated with a higher risk of KSD, with odds ratios of 6.18 (95 % CI 2.54-15.04) and 3.44 (95 % CI 1.67-7.08), respectively. There were no reverse causal effects. Further mediation analysis indicated that anxiety increases the risk of KSD by raising eGFR, through which 11.8 % of the effect of anxiety on KSD risk was mediated., Limitations: The research was confined to individuals of European heritage, and there could be specific genetic variances among diverse ethnicities., Conclusion: The current study suggests anxiety as an independent causal risk factor for KSD and unveils a new pathogenic mechanism, showing that anxiety raises eGFR, thereby increasing the risk of KSD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: The aim of this study is to investigate the results and safety of retrograde intrarenal surgery (RIRS) in patients who have previously undergone percutaneous nephrolithotomy (PCNL)., Methods: A retrospective analysis included patients who underwent RIRS for kidney stones between August 2018 and April 2023. Group 1 comprised 396 patients who underwent primary RIRS, while Group 2 included 231 individuals who had RIRS after previous PCNL. Evaluation parameters included preoperative characteristics, stone attributes, operative details, treatment outcomes, stone-free status, and complications. Statistical analysis utilized Student's t test, Mann-Whitney U test, and Pearson Chi-square test (p < 0.05)., Results: The mean age, body mass index, stone number, mean stone burden, and SFS were not statistically different between the groups. Lower pole stones were identified in 144 patients in Group 1 and 88 patients in Group 2 (p = 0.315). In Group 1 and Group 2, the mean operation time and fluoroscopy time were 65.23 ± 18.1 min, 81.32 ± 14.3 min, 26.34 ± 8.31 s, 46.61 ± 7.6 s, respectively, showing statistically significant differences between the groups (p = 0.013, p < 0.001, respectively). Infundibulum stenosis was identified and treated with a laser in 12% of Group 2 cases. Complications occurred in 12 patients in Group 1 and 14 patients in Group 2 (p = 0.136)., Conclusion: A history of PCNL may contribute to extended operation times and increased fluoroscopy exposure in subsequent RIRS without significantly affecting postoperative SFS or complication rates., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Kidney stone disease is a widespread urological disorder affecting millions globally. Timely diagnosis is crucial to avoid severe complications. Traditionally, renal stones are detected using computed tomography (CT), which, despite its effectiveness, is costly, resource-intensive, exposes patients to unnecessary radiation, and often results in delays due to radiology report wait times. This study presents a novel approach leveraging machine learning to detect renal stones early using routine laboratory test results. We utilized an extensive dataset comprising 2156 patient records from a Saudi Arabian hospital, featuring 15 attributes with challenges such as missing data and class imbalance. We evaluated various machine learning algorithms and imputation methods, including single and multiple imputations, as well as oversampling and undersampling techniques. Our results demonstrate that ensemble tree-based classifiers, specifically random forest (RF) and extra tree classifiers (ETree), outperform others with remarkable accuracy rates of 99%, recall rates of 98%, and F1 scores of 99% for RF, and 92% for ETree. This study underscores the potential of non-invasive, cost-effective laboratory tests for renal stone detection, promoting prompt and improved medical support.

A 50-year-old female developed kidney stones on an eroded embolization coil 16 months after percutaneous nephrolithotomy (PCNL) related bleeding complications. Retrograde ureteroscopy and thulium laser lithotripsy was performed to fragment the exposed portion of the coil into clinically insignificant pieces. Thulium laser coil fragmentation remains a potential strategy to remove eroded coils and their associated kidney stones; however, recurrent stone formation on the coil stump may necessitate repeat intervention if this conservative approach is pursued over radical antegrade coil removal. This case highlights the importance of continued surveillance and multidisciplinary management in preventing and treating coil erosion after PCNL., Competing Interests: None., (Published by Elsevier Inc.)

Screening high-risk populations is crucial for the prevention and treatment of kidney stones. Here, we employed radiomics to screen high-risk patients for kidney stones. A total of 513 independent kidneys from our hospital between 2020 and 2022 were randomly allocated to training and validation sets at a 7:3 ratio. Radiomic features were extracted using 3Dslicer software. The least absolute shrinkage and selection operator (LASSO) method was used to select radiomic features from the 107 extracted features, and logistic regression, decision tree, AdaBoost, and support vector machine (SVM) models were subsequently used to construct radiomic feature prediction models. Among these, the logistic regression algorithm demonstrated the best predictive performance and stability. The area under the curve (AUC) of the logistic regression model based on radiomic features was 0.858 in the training cohort and 0.806 in the validation cohort. Furthermore, univariate and multivariate logistic regression analyses were performed to identify the independent risk factors for kidney stones, which were gender and body mass index (BMI). Combining these independent risk factors improved the predictive performance of the model, with AUC values of 0.860 in the training cohort and 0.814 in the validation cohort. Clinical decision curve analysis (DCA) indicated that the radiomic model provided clinical benefit when the probability ranged from 0.2 to 1.0. The radiomic model has a good ability to screen high-risk patients with kidney stones, facilitating early intervention in kidney stone cases and improving patient prognosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction/objective: Graft stones in renal transplant recipients pose a unique challenge, finding effective interventions to ensure optimal graft function and patient well-being. Various methods of stone clearance have been described for graft stones, including percutaneous nephrolithotomy (PCNL). While PCNL is a promising approach for managing graft stones, specific outcomes and associated characteristics for this approach have not been comprehensively evaluated before. This study aims to evaluate the safety and efficacy of the use of PCNL as the primary intervention of graft stones by assessing stone-free rates (SFR), treatment impact on graft function, and perioperative complications., Methods: A retrospective clinical audit was performed for all transplants performed in a single center from 2007 to 2022, which included all graft lithiasis patients who were treated with PCNL. Both perioperative parameters and post-operative outcomes were collected. In addition, a systematic review including articles from MEDLINE, Embase, Web of Science yielded 18 full-text articles published between 1/1/2000 and 15/11/2023. The results pertaining to patients who underwent PCNLs for graft stones were cross-referenced and thoroughly evaluated. The review encompassed a comprehensive analysis of clinical data, postoperative outcomes, and procedural details. The protocol for the systematic review was prospectively registered on PROSPERO (CRD42023486825)., Results: In our center, 6 graft lithiasis patients were treated with PCNL. The initial SFR was 83.3%. SFR at 3 months and 1 year were both 100.0%. SFR at 3 years was 66.7%. Other centers reported initial SFR of 82.6-100.0% (interquartile range). SFR at 3 months, 1 year, 3 years was not well reported across the included studies. Incidence of graft lithiasis ranged from 0.44%-2.41%. Most common presentations at diagnosis were oliguria/anuria/acute kidney injury and asymptomatic. Reported complications included blood loss, transient hematuria, high urine output, sepsis, and damage to surrounding structures. The most commonly reported metabolic abnormalities in transplant lithiasis patients included hyperuricemia and hyperparathyroidism., Conclusion: PCNL is a practical and efficient choice for addressing graft lithiasis, demonstrating excellent stone clearance and minimal perioperative complications. These findings show the importance of PCNL as a primary intervention in this complex patient population., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study aimed to investigate the association between weight-adjusted waist index (WWI), a novel adiposity index, and kidney stone (KS)., Methods: Data were obtained from the National Health and Nutrition Examination Survey 2007-2018. According to the history of KS, participants were divided into the non-stone group and the stone group. Weighted multivariable logistic regression analyses were used to evaluate the correlation between WWI and KS in unadjusted, partially adjusted, and all-adjusted models. A restricted cubic spline (RCS) analysis assessed the association between continuous WWI and KS risk and obtained the risk function inflection point. Then, subgroup analysis based on the risk function inflection point was conducted to dissect the association in specific subgroups. In addition, the above analyst methods were repeatedly performed in populations after propensity score matching (PSM). The receiver operating characteristic (ROC) curve was applied to compare the ability to predict KS occurrence among WWI, visceral adiposity index (VAI), and body mass index (BMI)., Results: Weighted multivariable logistic regression analyses found a positive association between continuous WWI and KS risk in the all-adjusted model [odds ratio (OR) = 1.03; 95% confidence interval (CI), 1.02-1.04; P < 0.001]. In further analysis, the Q4 WWI group was linked to the highest KS risk when compared to the Q1-Q3 group (OR = 1.06; 95% CI, 1.05-1.08, P < 0.001). RCS analysis found a linear significant correlation between continuous WWI and KS risk, and the risk function inflection point is 11.08 cm/√kg. Subgroup analysis confirmed that WWI was associated with KS risk in different groups. After PSM, increased WWI was still related to a high risk of KS. Moreover, the ROC curve demonstrated that WWI has a higher predictive ability of KS occurrence than VAI and BMI (area under curve, 0.612 vs. 0.581 vs. 0.569)., Conclusion: In the US adult population, elevated WWI value was associated with an increased risk of KS. Furthermore, WWI was a better predictor of KS occurrence than VAI and BMI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Xie, Luo, Fan and Liu.)

Purpose: The ratio of monocyte to high-density lipoprotein cholesterol (MHR) has surfaced as a novel biomarker indicative of inflammation and oxidative stress. The aim of our study was to evaluate the association between MHR and the risk of kidney stones., Methods: This study analyzed data from individuals aged 20-79 who participated in the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018. The MHR was assessed as the exposure variable, while a self-reported history of kidney stones was used as the outcome variable. The independent relationship between MHR and the risk of kidney stones was thoroughly evaluated., Results: This study included 28,878 participants, and as the quartile range of the MHR increased, the proportion of kidney stones also rose progressively (7.20% to 8.89% to 10.88% to 12.05%, P <0.001). After adjusting for confounding factors, MHR was independently associated with an increased risk of kidney stones (OR=1.31, 95%CI=1.11-1.54, P =0.001), also independent of some common inflammatory indices. Subgroup analysis suggested that the relationship between MHR and kidney stones was more pronounced in female and individuals aged 20-49. Further restricted cubic spline (RCS) analysis indicated a nonlinear relationship between MHR and the risk of kidney stones., Conclusion: Our results indicate a positive correlation between MHR and an increased risk of kidney stones in US adults, underscoring the need for further large-scale prospective cohort studies to validate these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Zhao, Cao, Gu and Yang.)

Purpose: Fluoroscopy is usually required during retrograde intrarenal surgery (RIRS). Although fluoroscopy is considered necessary for effective and safe RIRS, there is growing awareness regarding radiation exposure risk to patients and surgeons. We conducted a multicenter-based, randomized, controlled trial to compare the safety and effectiveness of radiation-free (RF) RIRS with radiation-usage (RU) RIRS for kidney stone management., Materials and Methods: From August 2020 to April 2022, patients with a unilateral kidney stone (≤20 mm) eligible for RIRS were prospectively enrolled in 5 tertiary medical centers after randomization and divided into the RF and RU groups. RIRS was performed using a flexible ureteroscope with a holmium:YAG laser. The primary end point of this study was the success rate, defined as complete stone-free or residual fragments with asymptomatic kidney stones ≤ 3 mm. The secondary end point of this study was ascertaining the safety of RF RIRS. The success rates were analyzed using a noninferiority test., Results: Of the 140 consecutive randomized participants, 128 patients completed this study (RF: 63; RU: 65). The success rates (78% vs 80%, P = .8) were not significantly different between the groups. The rate of high-grade (grade 2-4) ureter injury was not significantly higher in the RF group compared to the RU group (RF = 3 [4.8%] vs RU = 2 [3.1%], P = .6). In RF RIRS, the success rate was noninferior compared to RU RIRS (the difference was 2.2% [95% CI, 0.16-0.12])., Conclusions: This study demonstrated that the surgical outcomes of RF RIRS were noninferior to RU RIRS.

In men aged 40-83 years, the overall incidence of urinary retention is 4.5-6.8 cases per 1000 men per year. The incidence increases significantly with age, so that a man in his 70 s has a 10% chance and a man in his 80 s has a more than 30% chance of experiencing an episode of acute urinary retention [1]. The goal of diagnosis is to quickly reach a finding through clinical examination and ultrasound to be able to relieve the bladder. The first maneuver is catheterization, followed by, if necessary, initiation of pharmacological therapy that targets the underlying cause. Despite the high association of urinary retention with benign prostatic hyperplasia (BPH), a comprehensive history and diagnosis are crucial to identify possible rare and complex causes and to enable targeted treatment. The challenge lies in finding the balance between rapid symptomatic treatment and thorough investigation of atypical and rare pathologies to develop individually adapted and effective therapy strategies., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: The global increase in kidney stone incidence and its complications emphasise the need for effective management. While pharmacists can play a significant role in counselling and guiding patients, their practices in managing patients with kidney stones remain unclear., Objective(s): To explore counselling practices and experiences of pharmacists when dealing with patients with kidney stones and to identify the barriers they face while providing counselling., Methods: A qualitative study was performed using semi-structured phone interviews with pharmacists practising in Jordan. Pharmacists were selected using quota sampling from those who took part in a previous study focused on pharmacists' knowledge of kidney stone aetiology and treatment. The COM-B Model of Behaviour Change was used to develop the interview guide and the analytical framework. Interviews were transcribed verbatim and analysed using a deductive thematic approach based on the pre-specified analytical framework., Results: Seven pharmacists (85.7% female; 57.1% working in community pharmacies) were interviewed. Counselling practices of patients with kidney stones were categorised into five themes: (1) Pharmacists' beliefs about patient counselling: perceived importance and desire to improve health through counselling; (2) Most priority patients: Types of patients mostly counselled; (3) Content of kidney stones-specific counselling: patient assessment and recommendations about kidney stones management; (4) Duration of the counselling sessions: time offered and influencing factors; (5) Barriers to patient counselling: patient-related, and pharmacist- and doctor-related challenges., Conclusions: Pharmacists recognise the crucial role of kidney stones counselling but face gaps in their practices, including incomplete dietary education, limited knowledge of medication prescriptions, inconsistent patient-specific approaches, and potential communication challenges. These gaps can be overcome by enhancing training, standardising protocols of kidney stone treatment, promoting interprofessional communication, and improving communication strategies. Future research, including quantitative assessments, is needed to inform strategies that optimise patient counselling practices and facilitate improved outcomes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Urolithiasis is a high‑incidence disease caused by calcium oxalate (mainly), uric acid, calcium phosphate, struvite, apatite, cystine and other stones. The development of kidney stones is closely related to renal tubule cell damage and crystal adhesion and aggregation. Cell death, comprising the core steps of cell damage, can be classified into various types (i.e., apoptosis, ferroptosis, necroptosis and pyroptosis). Different crystal types, concentrations, morphologies and sizes cause tubular cell damage via the regulation of different forms of cell death. Oxidative stress caused by high oxalate or crystal concentrations is considered to be a precursor to a variety of types of cell death. In addition, complex crosstalk exists among numerous signaling pathways and their key molecules in various types of cell death. Urolithiasis is considered a metabolic disorder, and tricarboxylic acid cycle‑related molecules, such as citrate and succinate, are closely related to cell death and the inhibition of stone development. However, a literature review of the associations between kidney stone development, metabolism and various types of cell death is currently lacking, at least to the best of our knowledge. Thus, the present review summarizes the major advances in the understanding of regulated cell death and urolithiasis progression.

Background: Structured Problem Solving (SPS) is a patient-centered approach to promoting behavior change that relies on productive collaboration between coaches and participants and reinforces participant autonomy. We aimed to describe the design, implementation, and assessment of SPS in the multicenter Prevention of Urinary Stones with Hydration (PUSH) randomized trial., Methods: In the PUSH trial, individuals with a history of urinary stone disease and low urine output were randomized to control versus a multicomponent intervention including SPS that was designed to promote fluid consumption and thereby prevent recurrent stones. We provide details specifically about training and fidelity assessment of the SPS coaches. We report on implementation experiences related to SPS during the initial conduct of the trial., Results: With training and fidelity assessment, coaches in the PUSH trial applied SPS to help participants overcome barriers to fluid consumption. In some cases, coaches faced implementation barriers such as variable participant engagement that required tailoring their work with specific participants. The coaches also faced challenges including balancing rapport with problem solving, and role clarity for the coaches., Conclusions: We adapted SPS to the setting of kidney stone prevention and overcame challenges in implementation, such as variable patient engagement. Tools from the PUSH trial may be useful to apply to other health behavior change settings in nephrology and other areas of clinical care., Trial Registration: ClinicalTrials.gov Identifier NCT03244189., (© 2024. The Author(s).)

Retrograde intrarenal surgery (RIRS) is the recommended treatment for renal stones up to two cm in size. As digital health literacy (e-HL) has become increasingly important in promoting informed health decisions and healthy behaviors, it is necessary to investigate its impact on RIRS treatment outcomes. We aimed to explore the influence of patients' e-HL level on their postoperative quality of life (QoL). We conducted an observational prospective study of 111 patients who underwent RIRS for renal pelvis stones. Before RIRS, we evaluated patients' e-HL using the electronic health literacy scale (eHEALS). QoL was evaluated using the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) one month after RIRS. SFR was determined by a negative CT scan or asymptomatic patients with stone fragments < 3 mm. Adult individuals aged 18 years or older with typical calyceal anatomy met the eligibility criteria for enrollment. Exclusion criteria for the study included patients with ureteric stones, anomalous kidneys, or bilateral renal stones. The relationship between patients' QoL and stone-free rate was explored using Spearman's rank correlation coefficient. The mean stone burden was 14 ± 3 mm (6-19 mm). The overall SFR was 83.3% after one month. The median EQ-5D-5L utility index and VAS score were 0.826 (0.41-1) and 70 (20-100) respectively, for the overall population. We found that poorer e-HL was associated with being older (p = 0.035), having less education (p = 0.005), and not having access to the internet (p < 0.001). A significant difference was observed between patients with sufficient e-HL and patients with limited e-HL in the self-care (p = 0.02) and anxiety/depression (p = 0.021) dimensions. To date, no study has examined the impact of patients' e-HL levels on postoperative QoL in patients undergoing RIRS. This study also revealed that e-HL levels in patients undergoing RIRS were related to postoperative QoL, especially self-care and anxiety/depression dimensions, whereas there was no relationship between them and SFR., (© 2024. The Author(s).)

Background: The high prevalence of kidney stones in adults worldwide has prompted research into potential interventions, one of which involves exploring the consumption of antioxidants that may confer protective effects. However, the relationship between the composite dietary antioxidant index (CDAI), a crucial measure used to assess an individual's overall antioxidant capacity from daily dietary intake, and kidney stones remains unclear. Therefore, we conducted cross-sectional analysis to examine the association between CDAI and kidney stone prevalence., Methods: The analysis was conducted utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. Antioxidant intake was derived from two 24-h dietary recalls surveys, while CDAI, a comprehensive measure that includes antioxidants like vitamins A, C, and E, zinc, selenium, and carotenoids, was calculated. Multivariate logistic regression and restricted cubic spline (RCS) regression were utilized to examine the association between CDAI and the prevalence of kidney stones., Results: The study included a total of 28,516 participants, with 2,748 individuals having a history of kidney stones. The median of CDAI was -0.01 (-2.02, 2.37). Individuals in the fourth quartile of CDAI exhibited a significantly lower prevalence of kidney stones compared to those in the first quartile (Odds Ratio [OR] = 0.769 [0.633-0.935]), even after adjusting for potential confounding factors (including age, sex, race, education level, poverty income ratio, smoking status, drinking status, body mass index (BMI), energy intake levels, physical activity level, serum calcium concentration, estimated glomerular filtration rate (eGFR), hypertension, diabetes and supplement use). The RCS analysis revealed a non-linear relationship between CDAI and kidney stone prevalence, with inflection points identified at 0.06 ( p for non-linearity = 0.039). Subgroup analysis demonstrated consistent CDAI-kidney stone prevalence associations across all subsets. Furthermore, a significant inverse correlation was observed between CDAI and inflammatory markers., Conclusion: This study provides evidence supporting a reciprocal correlation between adult dietary antioxidant intake, as measured by CDAI, and kidney stone prevalence. These findings emphasize the potential benefits of consuming dietary antioxidants in lowering the risk of kidney stone formation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest., (Copyright © 2024 Duan, Huang, Zhang, Wang, Lu, Wan, Sun and Wu.)

Background: Despite the prevalence and incidence of kidney stones progressively increasing worldwide, public awareness of this condition remains unclear. Understanding trends of awareness can assist healthcare professionals and policymakers in planning and implementing targeted health interventions. This study investigated online search interest in "kidney stone" by analyzing Google Trends, focusing on stationarity of the trends and predicting future trends., Methods: We performed time series analysis on worldwide Google monthly search data from January 2004 to November 2023. The Augmented Dickey-Fuller (ADF) test was used to assess the stationarity of the data, with a p -value below 0.05 indicating stationarity. Time series forecasting was performed using the autoregressive integrated moving average to predict future trends., Results: The highest search interest for "kidney stone" (score 100) was in August 2022, while the lowest was in December 2007 (score 36). As of November 2023, search interest remained high, at 92. The ADF test was significant ( p = 0.023), confirming data stationarity. The time series forecasting projected continued high public interest, likely reflecting ongoing concern and awareness. Notably, diverse regions such as Iran, the Philippines, Ecuador, the United States, and Nepal showed significant interest, suggesting widespread awareness of nephrolithiasis., Conclusion: This study highlighted that "kidney stone" is a consistently relevant health issue globally. The increase and stationarity of search trends, the forecasted sustained interest, and diverse regional interest emphasize the need for collaborative research and educational initiatives. This study's analysis serves as a valuable tool for shaping future healthcare policies and research directions in addressing nephrolithiasis related health challenges.

Objective: To investigate the efficacy and application of Enhanced Recovery After Surgery (ERAS) in elderly patients undergoing surgery for kidney stones., Methods: Clinical data of 104 elderly patients who underwent kidney stone surgery at West China Hospital, Sichuan University from January 2020 to December 2022 were retrospectively analyzed in this study. The patients were divided into two groups according to different nursing plans. Among them, 52 patients in the control group received conventional nursing, and 52 patients in the study group received ERAS mode nursing. Postoperative recovery, anxiety, complications, stress response and quality of life were compared between the two groups., Results: The time to recovery of postoperative rehabilitation indices in the research group was significantly shorter compared to the control group ( P < 0.05). The research group also exhibited a significantly lower incidence of complications such as hematuria, abdominal pain, vomiting, chills, fever, and hypotension (all P < 0.05). Before the initiation of nursing care, there were no significant differences in the State Anxiety Inventory (SAI) and Trait Anxiety Inventory (TAI) scores between the two groups (both P > 0.05). However, after nursing care, the research group exhibited lower SAI and TAI scores compared to the control group (all P < 0.05). Similarly, there was no significant difference in the General Quality of Life Inventory-74 (GQOLI-74) scores in any dimension between the two groups before nursing care ( P > 0.05), but the research group showcased higher scores in every dimension after nursing care ( P < 0.05). The levels of Heme Oxygenase-1 (HO-1), Endothelin-1 (ET-1), Adrenocorticotropic Hormone (ACTH), and Cortisol (Cor) were significantly lower in the research group after nursing care (all P < 0.05). The acknowledgment and approval scores of nursing care in the research group were higher than those in the control group ( P < 0.05)., Conclusion: The application of ERAS in elderly patients with kidney stones undergoing transurethral ureteral holmium laser lithotripsy is efficacious in mitigating stress reactions, enhancing quality of life and reducing perioperative anxiety, minimizing the incidence of complications, and promoting overall patient recovery., Competing Interests: None., (AJTR Copyright © 2024.)

Bryophyllum pinnatum (BP) is a medicinal plant used to treat many conditions when taken as a leaf juice, leaves in capsules, as an ethanolic extract, and as herbal tea. These preparations have been chemically analyzed except for decoctions derived from boiled green leaves. In preparation for a clinical trial to validate BP tea as a treatment for kidney stones, we used NMR and MS analyses to characterize the saturation kinetics of the release of metabolites. During boiling of the leaves, (a) the pH decreased to 4.8 within 14 min and then stabilized; (b) regarding organic acids, citric and malic acid were released with maximum release time (t max ) = 35 min; (c) for glycoflavonoids, quercetin 3-O-α-L-arabinopyranosyl-(1 → 2)-α-L-rhamnopyranoside (Q-3O-ArRh), myricetin 3-O-α-L-arabinopyranosyl-(1 → 2)-α-L-rhamnopyranoside (M-3O-ArRh), kappinatoside, myricitrin, and quercitrin were released with t max = 5-10 min; and (d) the total phenolic content (TPC) and the total antioxidant capacity (TAC) reached a t max at 55 min and 61 min, respectively. In summary, 24 g of leaves boiled in 250 mL of water for 61 min ensures a maximal release of key water-soluble metabolites, including organic acids and flavonoids. These metabolites are beneficial for treating kidney stones because they target oxidative stress and inflammation and inhibit stone formation.

Purpose: Residual fragments not removed with urinary stone surgery may become symptomatic. In this context, this study was carried out to investigate the effect of performing retrograde intrarenal surgery, which is conventionally performed in the lithotomy position, in the modified lithotomy position (Trend-side) on stone-free rates following the surgery., Methods: This prospective study consisted of 100 patients with a single kidney stone smaller than 2 cm between 2021 and 2023. These patients were randomized into two groups of 50 patients each to be operated on in the conventional lithotomy and Trend-side positions. Variables were compared using independent t test for continuous variables and chi-square test for categorical variables., Results: There was no significant difference between the lithotomy and Trend-side position groups in terms of preoperative size, density, location of the stone, and hydronephrosis degree. Stone-free rate was 72% (n = 36) in the lithotomy group and 92% (n = 46) in the Trend-side group. Hence, there was a significant difference between the groups in the stone-free rate in favor of the Trend-side group (p = 0.009). Fragmentation time was statistically significantly shorter in the Trend-side group than in the lithotomy group (34 ± 17 min vs. 43 ± 14 min; p = 0.006). There was no significant difference between the groups in postoperative complication rates., Conclusion: Performing retrograde intrarenal surgery in the Trend-side position shortened the duration of fragmentation compared to the lithotomy position and was associated with higher stone-free rates. In conclusion, the Trend-side position can be safely preferred in patients undergoing retrograde intrarenal surgery due to kidney stones., (© 2024. The Author(s).)

C-C chemokine receptor type 2 (CCR2) is a monocyte chemokine associated with oxidative stress and inflammation. Kidney stones (KS) are composed of calcium oxalate (CaOx), which trigger renal oxidative stress and inflammatory. This study aims to evaluate the effects of CCR2 on KS in vivo and in vitro. Eight-week-old male C57BL/6J mice were intraperitoneally injected with glyoxylate (GOX) daily to establish a KS model, and along with CCR2 antagonist (INCB3344) treatment on days 2, 4, and 6. The results showed that CCR2 antagonist reduced renal injury markers (blood urea nitrogen and serum creatinine), alleviated renal tubular injury and CaOx crystal deposition. CCR2 antagonist also decreased CCR2 expression induced by GOX treatment and increased Nrf2 expression. GOX treatment promoted malondialdehyde (MDA) production, decreased glutathione (GSH) content, and inhibited catalase (CAT) and superoxide dismutase (SOD) activity, however, CCR2 antagonist attenuated the above effects of GOX. CCR2 antagonist had inhibitory effects on GOX-induced inflammatory cytokine expression (IL1B, IL6 and MCP1), and inhibited apoptosis by increasing Bcl-2 expression and decreasing Bax and cleaved-caspase 3 expression. In vitro experiments were performed by co-culture model of CaOx-induced damaged HK-2 cells and macrophage-like THP-1 cells. CCR2 antagonist inhibited CaOx-induced THP-1 cell M1 polarization by decreasing the TNF-α, IL6 and iNOS levels, and further alleviated CaOx-induced oxidative stress damage, inflammatory response and apoptosis of HK-2 cells. The study suggests that CCR2 antagonist may be resistant to CaOx crystals-induced oxidative stress and inflammation by inhibiting macrophage M1 polarization.

Background: Kidney stones, a common urinary system ailment, often necessitate surgical intervention. Endoscopic combined intrarenal surgery (ECIRS) and multi-channel percutaneous nephron lithotripsy (MPCNL) are key modalities for treating complex renal stones, prompting the need for a comparative analysis to enhance clinical decision-making., Methods: Patients undergoing surgical treatment for complex kidney stones from April 2018 to April 2022 were divided into the control (MPCNL) and observation (ECIRS) groups. Propensity score matching was used to balance baseline data, and t -tests and chi-square tests were employed to compare the perioperative indicators between the two groups., Results: A total of 210 patients were enrolled in this study for pre-observational comparison, and they were divided into the control group (110 patients) and observation group (100 patients). Following matching, each group comprised 85 patients. Pre-observational comparison revealed significant differences between the groups in age, disease duration, and stone diameter ( p < 0.05). However, after matching, baseline data comparison showed no statistically significant differences ( p > 0.05). Surgery-related parameters, including operation time, intraoperative blood loss, postoperative activity duration and hospital stay, did not significantly differ between the groups ( p > 0.05). The observation group exhibited a significantly higher stone retention-free rate after initial treatment compared with the control group ( p < 0.05), although overall stone clearance rates did not significantly differ between the groups ( p > 0.05). We found no significant differences in perioperative complications between the two groups ( p > 0.05). Moreover, the observation group experienced significantly lower postoperative pain levels at 6, 24 and 48 h compared with the control group ( p < 0.001)., Conclusions: Conclusively, ECIRS and MPCNL are viable options for treating complex renal calculi, with similar operation times, complication rates and stone clearance rates. ECIRS may offer advantages including lower postoperative pain and higher initial stone clearance rates than MPCNL. However, large-scale studies with long follow-up times are needed for validation., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s).)

Objective: To report the initial results of an randomized clinical trail comparing the safety and efficacy between 7.5F and 9.2F flexible ureteroscope (FUS) in the management of renal calculi <2 cm. Materials and Methods: Eighty patients were enrolled and received retrograde intrarenal surgery (RIRS) with a different size FUS. The operation results and complications were compared. Results: Two cases in the 7.5F group and four cases in the 9.2F group failed to insert the 12/14F ureteral access sheath (UAS), respectively, and no significant difference ( p  = 0.396) was noted. However, 10/12F UAS was inserted in the 7.5F group, but not available in the 9.2F group, and thus, the 10/12F UAS inserting rate in the 7.5F group was higher than in the 9.2F group (100% vs 0%, p  = 0.014), and the UAS insertion failure rate in 9.2F group was higher than in the 7.5F group (10% vs 0%, p  = 0.040). The operation time in 7.5F group was shorter than the 9.2F group (35.60 ± 7.86 vs 41.05 ± 8.14, p  = 0.003). Less irrigation was required in 7.5F group (813.93 ± 279.47 mL vs 1504.18 ± 385.31 mL, p  = 0.000). The postoperative fever rate in 9.2F group was higher than 7.5F group (20% vs 5%, p  = 0.043). There was no significant difference in sepsis (0% vs 2.5%, p  = 0.314) between the two groups. No significant difference was noted in hospital stay (0.93 ± 0.49 days vs 1.14 ± 0.64 days, p  = 0.099) between the two groups. The final stone-free rate (SFR) in 7.5F group was higher than 9.2F group (95% vs 80%, p  = 0.043). Conclusion: The latest 7.5F mini FUS was a reliable instrument in RIRS to keep a good visualization with low requirement of irrigation, low postoperative infection complication, and also a high SFR when compared with the conventional 9.2F FUS. Clinical Trial Registration: NCT05231577.

Objective: To assess the impact of kidney stone disease (KSD) and its treatment on the health-related quality of life (HRQOL) of high-risk stone formers with hyperparathyroidism, renal tubular acidosis, malabsorptive disease, and medullary sponge kidney., Patients and Methods: The Wisconsin Stone Quality of Life questionnaire was used to evaluate HRQOL in 3301 patients with a history of KSD from 16 institutions in North America between 2014 and 2020. Baseline characteristics and medical history were collected from patients, while active KSD was confirmed through radiological imaging. The high-risk group was compared to the remaining patients (control group) using the Wilcoxon rank-sum test., Results: Of 1499 patients with active KSD included in the study, the high-risk group included 120 patients. The high-risk group had significantly lower HRQOL scores compared to the control group (P < 0.01). In the multivariable analyses, medullary sponge kidney disease and renal tubular acidosis were independent predictors of poorer HRQOL, while alkali therapy was an independent predictor of better HRQOL (all P < 0.01)., Conclusions: Among patients with active KSD, high-risk stone formers had impaired HRQOL with medullary sponge kidney disease and renal tubular acidosis being independent predictors of poorer HRQOL. Clinicians should seek to identify these patients earlier as they would benefit from prompt treatment and prevention., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Nephrolithiasis seriously affects people's health with increasing prevalence and high recurrence rates. However, there is still a lack of effective interventions for the clinical prevention of kidney stones. Hyperoxaluria-induced renal tubular epithelial cell (TEC) injury is a known key factor in kidney stone formation. Thus, developing new drugs to inhibit the hyperoxaluria-induced TEC injury may be the best way., Methods: We synthesized the Se@SiO 2 nanocomposites as described in Zhu's study. The size and morphology of the Se@SiO 2 nanocomposites were captured by transmission electron microscopy. Cell viability was measured by a Cell Counting Kit-8 (CCK-8) assay. The mice were randomly divided into the following four groups: (I) the control group (n=6); (II) the Se@SiO 2 group (n=6); (III) the glyoxylic acid monohydrate (GAM) group; and (IV) the GAM + Se@SiO 2 group (n=6). The concentration of Se in the mice was quantified using inductively coupled plasma atomic emission spectroscopy., Results: The CCK-8 assays showed that Se@SiO 2 nanocomposites had almost no obvious cytotoxicity on the Transformed C3H Mouse Kidney-1 (TCMK-1) cell. The mice kidney Se concentration levels in the Se@SiO 2 groups (Se@SiO 2 6.905±0.074 mg/kg; GAM + Se@SiO 2 7.673±2.85 mg/kg) (n=6) were significantly higher than those in the control group (Control 0.727±0.072 mg/kg; GAM 0.747±0.074 mg/kg) (n=6). The Se@SiO 2 nanocomposites reduced kidney injury, calcium oxalate crystal deposition, and the osteoblastic-associated proteins in the hyperoxaluria mice models., Conclusions: Se@SiO 2 nanocomposites appear to protect renal TECs from hyperoxaluria by reducing reactive oxygen species production, suggesting the potential role of preventing kidney stone formation and recurrence., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-511/coif). The authors have no conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.)

Kidney stones refer to abnormal crystal formation that occurs in the kidney. Among a variety of components of kidney stones, calcium oxalate (CaOx) is the most common type. Despite many efforts to investigate the pathogenesis of CaOx stones, the pathogenesis remains an issue of debate. With high occurrence and recurrence, individuals with stone formation are prone to frequently consult a doctor and to be hospitalized, and the treatment of kidney stones poses a heavy burden on the patients. Concerns should be focused not only on treatment but also on prevention. Herein, we reviewed the studies on prevention methods of CaOx stones through diet, lifestyle, and medication extending until the current time frame. As hyperoxaluria is the most common metabolic disorder among CaOx stone formations, we also included several studies on the treatment and prevention of hyperoxaluria. Our objective was to outline the effective methods to prevent renal CaOx stone formation., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Wang and Wang.)

Introduction: This study investigated the learning curve of retrograde intrarenal surgery (RIRS) in patients with medium-sized stones using cumulative sum analysis (CUSUM) to evaluate the competence and proficiency of three new surgeons during their first RIRS procedures., Materials and Methods: We conducted a retrospective review of 227 patients from 2019 to 2022 at a single institution. The patients were divided into four groups based on the operating surgeon: tutor surgeon (85 patients), newbie surgeon A (21 patients), newbie surgeon B (85 patients), and newbie surgeon C (36 patients). Patients had one or multiple stones with the largest stone diameter fell within the range of 10-30 mm. Fragmentation efficacy was calculated as "removed stone volume (mm3) divided by operative time (minutes)." CUSUM analysis monitored changes in fragmentation efficacy and validated surgical outcomes., Results: No statistically significant differences were observed in the total stone volume, maximum stone size, or total operation time between the three newbie surgeons and the tutor surgeon. The mean fragmentation efficacy value was comparable among the newbie surgeons, but significantly different from that of the tutor surgeon. The minimum acceptable fragmentation efficacy level was set at 25.12 mL/min, based on the tutor's average value. The CUSUM curves for the three surgeons initially remained relatively flat until Cases 12-15, after which they increased and eventually plateaued. Stone-free rates and postoperative complications did not differ significantly among the surgeons., Conclusion: Learning curve analysis for the three newbie surgeons indicated that approximately 12-15 cases were required to reach a plateau., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)