Tumour budding as a prognostic biomarker in biopsies and resections of neoadjuvant-treated rectal adenocarcinoma.

BACKGROUND: Tumour budding (TB) is a marker of tumour aggressiveness which, when measured in rectal cancer resection specimens, predicts worse outcomes and response to neoadjuvant therapy. We investigated the utility of TB assessment in the setting of neoadjuvant treatment. METHODS AND RESULTS: A single-centre, retrospective cohort study was conducted. TB was assessed using the hot-spot International Tumour Budding Consortium (ITBCC) method and classified by the revised ITBCC criteria. Haematoxylin and eosin (H&E) and AE1/AE3 cytokeratin (CK) stains for ITB (intratumoural budding) in biopsies with PTB (peritumoural budding) and ITB (intratumoural budding) in resection specimens were compared. Logistic regression assessed budding as predictors of lymph node metastasis (LNM). Cox regression and Kaplan-Meier analyses investigated their utility as a predictor of disease-free (DFS) and overall (OS) survival. A total of 146 patients were included; 91 were male (62.3%). Thirty-seven cases (25.3%) had ITB on H&E and 79 (54.1%) had ITB on CK assessment of biopsy tissue. In univariable analysis, H&E ITB [odds (OR) = 2.709, 95% confidence interval (CI) = 1.261-5.822, P = 0.011] and CK ITB (OR = 2.165, 95% CI = 1.076-4.357, P = 0.030) predicted LNM. Biopsy-assessed H&E ITB (OR = 2.749, 95% CI = 1.258-6.528, P = 0.022) was an independent predictor of LNM. In Kaplan-Meier analysis, ITB identified on biopsy was associated with worse OS (H&E, P = 0.003, CK: P = 0.009) and DFS (H&E, P = 0.012; CK, P = 0.045). In resection specimens, CK PTB was associated with worse OS (P = 0.047), and both CK PTB and ITB with worse DFS (PTB, P = 0.014; ITB: P = 0.019). In multivariable analysis H&E ITB predicted OS (HR = 2.930, 95% CI = 1.261-6.809) and DFS (HR = 2.072, 95% CI = 1.031-4.164). CK PTB grading on resection also independently predicted OS (HR = 3.417, 95% CI = 1.45-8.053, P = 0.005). CONCLUSION: Assessment of TB using H&E and CK may be feasible in rectal cancer biopsy and post-neoadjuvant therapy-treated resection specimens and is associated with LNM and worse survival outcomes. Future management strategies for rectal cancer might be tailored to incorporate these findings.

Follow-up of urolithiasis patients after treatment: an algorithm from the EAU Urolithiasis Panel.

OBJECTIVE: To develop a follow-up algorithm for urinary stone patients after definitive treatment. MATERIALS AND METHODS: The panel performed a systematic review on follow-up of urinary stone patients after treatment (PROSPERO: CRD42020205739). Given the lack of comparative studies we critically evaluated the literature and reached a consensus on the follow-up scheme. RESULTS: A total of 76 studies were included in the analysis, including 17 RCTs. In the stone-free general population group, 71-100% of patients are stone-free at 12 months while 29-94% remain stone-free at 36 months. We propose counselling these patients on imaging versus discharge after the first year. The stone-free rate in high-risk patients not receiving targeted medical therapy is < 40% at 36 months, a fact that supports imaging, metabolic, and treatment monitoring follow-up once a year. Patients with residual fragments ≤ 4 mm have a spontaneous expulsion rate of 18-47% and a growth rate of 10-41% at 12 months, supporting annual imaging follow-up. Patients with residual fragments > 4 mm should be considered for surgical re-intervention based on the low spontaneous expulsion rate (13% at 1 year) and high risk of recurrence. Plain film KUB and/or kidney ultrasonography based on clinicians' preference and stone characteristics is the preferred imaging follow-up. Computed tomography should be considered if patient is symptomatic or intervention is planned. CONCLUSIONS: Based on evidence from the systematic review we propose, for the first time, a follow-up algorithm for patients after surgical stone treatment balancing the risks of stone recurrence against the burden of radiation from imaging studies.

Use of Temporally Validated Machine Learning Models To Predict Outcomes of Percutaneous Nephrolithotomy Using Data from the British Association of Urological Surgeons Percutaneous Nephrolithotomy Audit.

BACKGROUND AND OBJECTIVE: Machine learning (ML) is a subset of artificial intelligence that uses data to build algorithms to predict specific outcomes. Few ML studies have examined percutaneous nephrolithotomy (PCNL) outcomes. Our objective was to build, streamline, temporally validate, and use ML models for prediction of PCNL outcomes (intensive care admission, postoperative infection, transfusion, adjuvant treatment, postoperative complications, visceral injury, and stone-free status at follow-up) using a comprehensive national database (British Association of Urological Surgeons PCNL). METHODS: This was an ML study using data from a prospective national database. Extreme gradient boosting (XGB), deep neural network (DNN), and logistic regression (LR) models were built for each outcome of interest using complete cases only, imputed, and oversampled and imputed/oversampled data sets. All validation was performed with complete cases only. Temporal validation was performed with 2019 data only. A second round used a composite of the most important 11 variables in each model to build the final model for inclusion in the shiny application. We report statistics for prognostic accuracy. KEY FINDINGS AND LIMITATIONS: The database contains 12 810 patients. The final variables included were age, Charlson comorbidity index, preoperative haemoglobin, Guy's stone score, stone location, size of outer sheath, preoperative midstream urine result, primary puncture site, preoperative dimercapto-succinic acid scan, stone size, and image guidance (https://endourology.shinyapps.io/PCNL_Demographics/). The areas under the receiver operating characteristic curve was >0.6 in all cases. CONCLUSIONS AND CLINICAL IMPLICATIONS: This is the largest ML study on PCNL outcomes to date. The models are temporally valid and therefore can be implemented in clinical practice for patient-specific risk profiling. Further work will be conducted to externally validate the models. PATIENT SUMMARY: We applied artificial intelligence to data for patients who underwent a keyhole surgery to remove kidney stones and developed a model to predict outcomes for this procedure. Doctors could use this tool to advise patients about their risk of complications and the outcomes they can expect after this surgery.

Urological Guidelines for Kidney Stones: Overview and Comprehensive Update.

BACKGROUND: Evidence-based guidelines are published by urological organisations for various conditions, including urolithiasis. In this paper, we provide guidance on the management of kidney stone disease (KSD) and compare the American Urological Association (AUA) and European Association of Urologists (EAU) guidelines. METHODS: We evaluate and appraise the evidence and grade of recommendation provided by the AUA and EAU guidelines on urolithiasis (both surgical and medical management). RESULTS: Both the AUA and EAU guidelines provide guidance on the type of imaging, treatment options, and medical therapies and advice on specific patient groups, such as in paediatrics and pregnancy. While the guidelines are generally aligned and based on evidence, some subtle differences exist in the recommendations, but both are generally unanimous for the majority of the principles of management. CONCLUSIONS: We recommend that the guidelines should undergo regular updates based on recently published material, and while these guidelines provide a framework, treatment plans should still be personalised, respecting patient preferences, surgical expertise, and various other individual factors, to offer the best outcome for kidney stone patients.

ChatGPT in urology practice: revolutionizing efficiency and patient care with generative artificial intelligence.

PURPOSE OF REVIEW: ChatGPT has emerged as a potentially useful tool for healthcare. Its role in urology is in its infancy and has much potential for research, clinical practice and for patient assistance. With this narrative review, we want to draw a picture of what is known about ChatGPT's integration in urology, alongside future promises and challenges. RECENT FINDINGS: The use of ChatGPT can ease the administrative work, helping urologists with note-taking and clinical documentation such as discharge summaries and clinical notes. It can improve patient engagement through increasing awareness and facilitating communication, as it has especially been investigated for uro-oncological diseases. Its ability to understand human emotions makes ChatGPT an empathic and thoughtful interactive tool or source for urological patients and their relatives. Currently, its role in clinical diagnosis and treatment decisions is uncertain, as concerns have been raised about misinterpretation, hallucination and out-of-date information. Moreover, a mandatory regulatory process for ChatGPT in urology is yet to be established. SUMMARY: ChatGPT has the potential to contribute to precision medicine and tailored practice by its quick, structured responses. However, this will depend on how well information can be obtained by seeking appropriate responses and asking the pertinent questions. The key lies in being able to validate the responses, regulating the information shared and avoiding misuse of the same to protect the data and patient privacy. Its successful integration into mainstream urology needs educational bodies to provide guidelines or best practice recommendations for the same.

Worldwide trends of practice and intervention in paediatric endourology: comparison of European versus Non-European responses.

Introduction: The area of paediatric endourology is unique and is recognised to be challenging, and it requires a certain level of focused training and expertise. Our aim was to conduct a worldwide survey in order to gain an overview regarding the current practice patterns for minimally invasive treatments of paediatric upper urinary tract stone patients. Material and methods: The survey was distributed between December 2021 and April 2022 through urology sections and societies in United Kingdom, Latin America and Asia. The survey was made up of 20 questions and it was distributed online using the free online Google Forms (TM). Results: 221 urologists answered the survey with 56 responses each from India, South America and UK and 53 responses from the rest of Europe (15 countries). In total, 163 responders (73.7%) managed paediatric stone patients in their daily practice. Of the responders, 60.2% were adult urologists and 39.8% were paediatric urologists. 12.9% adult urologists and 20.4% paediatric urologists run independent clinics while some run combined adult and paediatric clinics sometimes with the support of the nephrologists. Only 33.9% urologists offered all surgical treatments [extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL), ureteroscopy (URS) and retrograde intrarenal surgery (RIRS)]. Conclusions: Treatment of paediatric stones can vary according to country and legislations. Based on the results of this survey, minimally invasive methods such as URS and mini PCNL seem to have become more popular. In most institutions a collaboration exists between adult and paediatric urologists, which is the key for a tailored decision making, counselling and treatment success.

Does pre-stenting influence outcomes of shockwave lithotripsy? A systematic review and meta-analysis.

OBJECTIVE: To determine whether preoperative use of JJ stents in patients undergoing shockwave lithotripsy (SWL) impacts on stone clearance and the rate of postoperative complications. PATIENTS AND METHODS: We screened multiple databases from inception to January 2021, using the relevant search terms for SWL in patients with a preoperative stent. Inclusion criteria were randomised controlled trials of ≥20 patients aged >18 years who had had SWL with a JJ stent. This review has been registered in the International Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42023443195). Statistical analysis was performed using 'meta' in R. RESULTS: There were seven eligible studies (403 patients receiving JJ stents and 394 controls). There was no significant difference in the stone-free rate (SFR) following SWL with a JJ stent compared to SWL alone. When considering the complication rates, there was a significantly reduced risk of steinstrasse in patients with a JJ stent. However, there was no significant difference in the risk of other complications including pain, fever, and haematuria, and no significant difference in the likelihood of requiring auxiliary procedures or re-treatment. CONCLUSIONS: There was a reduced risk of steinstrasse in patients undergoing SWL with a JJ stent compared to SWL alone. However, there was no significant difference in the risk of other postoperative complications. Use of a JJ stent had no effect on the efficacy of SWL, with no significant difference in the SFR.

Inhibiting HCMV pUL89-C Endonuclease with Metal-Binding Compounds.

Human cytomegalovirus (HCMV) infects individuals of all ages and establishes a lifelong latency. Current antiviral drugs are suboptimal in efficacy and safety and ineffective against resistant/refractory HCMV. Therefore, there is an unmet clinical need for efficacious, safe, and mechanistically novel HCMV drugs. The recent Food and Drug Administration (FDA) approval of letermovir (LTV) validated the HCMV terminase complex as a new target for antiviral development. LTV targets terminase subunit pUL56 but not the main endonuclease enzymatic function housed in the C terminus of subunit pUL89 (pUL89-C). Structurally and mechanistically, pUL89-C is an RNase H-like viral endonuclease entailing two divalent metal ions at the active site. In recent years, numerous studies have extensively explored pUL89-C inhibition using metal-chelating chemotypes, an approach previously used for inhibiting HIV ribonuclease H (RNase H) and integrase strand transfer (INST). Collectively, the work summarized herein validates the use of metal-binding scaffolds for designing potent and specific pUL89-C inhibitors.

Routine Urinary Biochemistry Does Not Accurately Predict Stone Type Nor Recurrence in Kidney Stone Formers: A Multicentre, Multimodel, Externally Validated Machine-Learning Study.

Objectives: Urinary biochemistry is used to detect and monitor conditions associated with recurrent kidney stones. There are no predictive machine learning (ML) tools for kidney stone type or recurrence. We therefore aimed to build and validate ML models for these outcomes using age, gender, 24-hour urine biochemistry, and stone composition. Materials and Methods: Data from three cohorts were used, Southampton, United Kingdom (n = 3013), Newcastle, United Kingdom (n = 5984), and Bern, Switzerland (n = 794). Of these 3130 had available 24-hour urine biochemistry measurements (calcium, oxalate, urate [Ur], pH, volume), and 1684 had clinical data on kidney stone recurrence. Predictive ML models were built for stone type (n = 5 models) and recurrence (n = 7 models) using the UK data, and externally validated with the Swiss data. Three sets of models were built using complete cases, multiple imputation, and oversampling techniques. Results: For kidney stone type one model (extreme gradient boosting [XGBoost] built using oversampled data) was able to effectively discriminate between calcium oxalate, calcium phosphate, and Ur on both internal and external validation. For stone recurrence, none of the models were able to discriminate between recurrent and nonrecurrent stone formers. Conclusions: Kidney stone recurrence cannot be accurately predicted using modeling tools built using specific 24-hour urinary biochemistry values alone. A single model was able to differentiate between stone types. Further studies to delineate accurate predictive tools should be undertaken using both known and novel risk factors, including radiomics and genomics.

Oncological Efficacy of Robotic Nephroureterectomy vs. Open and Laparoscopic Nephroureterectomy for Suspected Non-Metastatic UTUC-A Systematic Review and Meta-Analysis.

INTRODUCTION AND AIMS: The optimal approach for nephroureterectomy in patients with suspected UTUC remains a point of debate. In this review, we compare the oncological outcomes of robotic nephroureterectomy (RNU) with open (ONU) or laparoscopic nephroureterectomy (LNU). METHODS: All randomized trials and observational studies comparing RNU with ONU and/or LNU for suspected non-metastatic UTUC are included in this review. The systematic review was performed in accordance with the Cochrane Guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The primary outcome measures were overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and intravesical recurrence-free survival (IV-RFS). The secondary outcome measures were the lymph node dissection (LND) rates, positive margin rates, and the proportion of patients receiving bladder intravesical chemotherapy. RESULTS: We identified 8172 references through our electronic searches and 8 studies through manual searching. A total of 15 studies met the inclusion criteria. The total number of patients in the review was 18,964. RNU had superior OS compared to LNU (HR: 0.81 (95% CI: 0.71, 0.93), p-0.002 (very low certainty)). RNU and ONU had similar OS (HR: 0.83 (95% CI: 0.52, 1.34), p-0.44 (very low certainty)). One study reported an independent association of RNU as a worse predictor of IV-RFS when compared to ONU (HR-1.73 (95% CI: 1.22, 2.45)). The LND rates were higher in the RNU cohort when compared to the LNU cohort (RR 1.24 (95% CI: 1.03, 1.51), p-0.03 (low certainty)). The positive margin rate was lower in the RNU cohort when compared to the ONU cohort (RR 0.29 (95% CI: 0.08, 0.86), p-0.03 (low certainty)). CONCLUSION: RNU offers comparable oncological efficacy to ONU, except for intravesical recurrence-free survival (IV-RFS). RNU has fewer positive surgical margin rates compared to ONU in well-balanced studies. RNU appears to outperform LNU for certain oncological parameters, such as OS and the proportion of patients who receive lymph node dissections. The quality of evidence comparing surgical techniques for UTUC has remained poor in the last decade.

Outcomes of Flexible Ureteroscopy vs Extracorporeal Shock Wave Lithotripsy for Renal Stones in Pediatric Patients: A European Association of Urology Urolithiasis Guidelines Systematic Review and Meta-Analysis.

PURPOSE: We sought to determine which treatment between flexible ureteroscopy and shock wave lithotripsy has a better stone-free rate in pediatric patients (<18 years) with renal or proximal ureteric stones (<2 cm). Subanalysis for all outcomes for randomized controlled trials only. MATERIALS AND METHODS: Using PubMed, Web of Science, and the Cochrane database, we identified studies (randomized clinical trials and prospective comparative nonrandomized studies) published until August 2022 reporting surgical outcomes of pediatrics patients undergoing flexible ureteroscopy and shock wave lithotripsy with renal or proximal ureteric stones <2 cm (PROSPERO ID: CRD42022378790). Only randomized controlled trials were considered for meta-analysis. Stone-free rate, operative time, and complications were analyzed. Analysis was performed in R. RESULTS: A total of 6 studies identified, of which 3 were randomized clinical trials and 4 had data on renal stones. A total of 669 patients were analyzed. Mean age ranged from 4.4 to 12.4 years. The shock wave lithotripsy group presented a range of stone-free rate between 21 and 90% while the flexible ureteroscopy group presented a range of stone-free rates between 37% and 97%. Meta-analysis of randomized controlled trials only (n=302) demonstrated significantly higher stone-free rate in flexible ureteroscopy vs shock wave lithotripsy (RR = 1.17, 95% CI: 1.04-1.33, P = 0.01), operative time (mean difference = +16.4 minutes, 95% CI: 7.3-25.5, P < 0.01) and hospital stay (mean difference = +0.25 days, 95% CI: 0.14-0.36, P < 0.001). But no difference in fluoroscopy exposure time (mean difference = -21.0 seconds, 95% CI: -42.6 to 0.56, P = 0.07), Clavien I-II (RR = 1.23, 95% CI: 0.71-2.12, P = 0.45) or Clavien III-V complications (RR = 1.04, 95% CI: 0.32-3.42, P = 0.95). CONCLUSIONS: Flexible ureteroscopy has a significantly higher stone-free rate than shock wave lithotripsy, with no difference in complication rate or fluoroscopy exposure time, and significantly higher operative times and hospital stay. However, the current evidence base for this is weak and further randomized trials are needed.

Comparison of Treatment Outcomes for Fluoroscopic and Fluoroscopy-free Endourological Procedures: A Systematic Review on Behalf of the European Association of Urology Urolithiasis Guidelines Panel.

CONTEXT: Endourological procedures frequently require fluoroscopic guidance, which results in harmful radiation exposure to patients and staff. One clinician-controlled method for decreasing exposure to ionising radiation in patients with urolithiasis is to avoid the use of intraoperative fluoroscopy during stone intervention procedures. OBJECTIVE: To comparatively assess the benefits and risks of "fluoroscopy-free" and fluoroscopic endourological interventions in patients with urolithiasis. EVIDENCE ACQUISITION: A systematic review of the literature from 1970 to 2022 was performed using the MEDLINE/PubMed, Embase, and Cochrane controlled trials databases and ClinicalTrials.gov. Primary outcomes assessed were complications and the stone-free rate (SFR). Studies reporting data on ureteroscopy and percutaneous nephrolithotomy (PCNL) were eligible for inclusion. Secondary outcomes were operative duration, hospital length of stay, conversion from a fluoroscopy-free to a fluoroscopic procedure, and requirement for an auxiliary procedure to achieve stone clearance. EVIDENCE SYNTHESIS: In total, 24 studies (12 randomised and 12 observational) out of 834 abstracts screened were eligible for analysis. There were 4564 patients with urolithiasis in total, of whom 2309 underwent a fluoroscopy-free procedure and 2255 underwent a comparative fluoroscopic procedure for treatment of urolithiasis. Pooled analysis of all procedures revealed no significant difference between the groups in SFR (p = 0.84), operative duration (p = 0.11), or length of stay (p = 0.13). Complication rates were significantly higher in the fluoroscopy group (p = 0.009). The incidence of conversion from a fluoroscopy-free to a fluoroscopic procedure was 2.84%. Similar results were noted in subanalyses for ureteroscopy (n = 2647) and PCNL (n = 1917). When only randomised studies were analysed (n = 12), the overall complication rate was significantly in the fluoroscopy group (p < 0.001). CONCLUSIONS: For carefully selected patients with urolithiasis, fluoroscopy-free and fluoroscopic endourological procedures have comparable stone-free and complication rates when performed by experienced urologists. In addition, the conversion rate from a fluoroscopy-free to a fluoroscopic endourological procedure is low at 2.84%. These findings are important for clinicians and patients, as the detrimental health effects of ionising radiation are negated with fluoroscopy-free procedures. PATIENT SUMMARY: We compared treatments for kidney stones with and without the use of radiation. We found that kidney stone procedures without the use of radiation can be safely performed by experienced urologists in patients with normal kidney anatomy. These findings are important, as they indicate that the harmful effects of radiation can be avoided during kidney stone surgery.

Use of whole genome sequencing to determine the genetic basis of visceral myopathies including Prune Belly syndrome.

Objectives/aims: The visceral myopathies (VM) are a group of disorders characterised by poorly contractile or acontractile smooth muscle. They manifest in both the GI and GU tracts, ranging from megacystis to Prune Belly syndrome. We aimed to apply a bespoke virtual genetic panel and describe novel variants associated with this condition using whole genome sequencing data within the Genomics England 100,000 Genomes Project. Methods: We screened the Genomics England 100,000 Genomes Project rare diseases database for patients with VM-related phenotypes. These patients were screened for sequence variants and copy number variants (CNV) in ACTG2, ACTA2, MYH11, MYLK, LMOD1, CHRM3, MYL9, FLNA and KNCMA1 by analysing whole genome sequencing data. The identified variants were analysed using variant effect predictor online tool, and any possible segregation in other family members and novel missense mutations was modelled using in silico tools. The VM cohort was also used to perform a genome-wide variant burden test in order to identify confirm gene associations in this cohort. Results: We identified 76 patients with phenotypes consistent with a diagnosis of VM. The range of presentations included megacystis/microcolon hypoperistalsis syndrome, Prune Belly syndrome and chronic intestinal pseudo-obstruction. Of the patients in whom we identified heterozygous ACTG2 variants, 7 had likely pathogenic variants including 1 novel likely pathogenic allele. There were 4 patients in whom we identified a heterozygous MYH11 variant of uncertain significance which leads to a frameshift and a predicted protein elongation. We identified one family in whom we found a heterozygous variant of uncertain significance in KCNMA1 which in silico models predicted to be disease causing and may explain the VM phenotype seen. We did not find any CNV changes in known genes leading to VM-related disease phenotypes. In this phenotype selected cohort, ACTG2 is the largest monogenic cause of VM-related disease accounting for 9% of the cohort, supported by a variant burden test approach, which identified ACTG2 variants as the largest contributor to VM-related phenotypes. Conclusions: VM are a group of disorders that are not easily classified and may be given different diagnostic labels depending on their phenotype. Molecular genetic analysis of these patients is valuable as it allows precise diagnosis and aids understanding of the underlying disease manifestations. We identified ACTG2 as the most frequent genetic cause of VM. We recommend a nomenclature change to 'autosomal dominant ACTG2 visceral myopathy' for patients with pathogenic variants in ACTG2 and associated VM phenotypes. Supplementary Information: The online version contains supplementary material available at 10.1007/s44162-023-00012-z.

Complications After Radical Cystectomy: A Systematic Review and Meta-analysis of Randomized Controlled Trials with a Meta-regression Analysis.

CONTEXT: Radical cystectomy is considered a procedure of high complexity with a relative high complication rate. OBJECTIVE: To systematically summarize the literature regarding the complications of radical cystectomy and the factors that contribute to them. EVIDENCE ACQUISITION: We searched MEDLINE/PubMed, ClinicalTrials.gov, and Cochrane Library, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for randomized controlled trials (RCTs) on complications related to radical cystectomy. EVIDENCE SYNTHESIS: A total of 3766 studies were screened, and 44 studies were included in this systematic review and meta-analysis. Complications following radical cystectomy are quite common. The most common complications were gastrointestinal complications (20%), infectious complications (17%), and ileus (14%). The majority of complications occurring were Clavien I-II (45%). Specific measurable patient factors are related to certain complications and can be used to stratify risk and assist in preoperative counseling, while proper design of high-quality RCTs may better reflect real-life complication rates. CONCLUSIONS: In our study, RCTs with a low risk of bias had higher complication rates than studies with a high risk of bias, underlining the need for further improvement on complication reporting in order to refine surgical outcomes. PATIENT SUMMARY: Radical cystectomy is usually followed by high complication rates, which affect patients and are, in turn, strongly associated with patients' preoperative health status.

Endourological Options for Small (< 2 cm) Lower Pole Stones - Does the Lower Pole Angle Matter?

PURPOSE OF REVIEW: Small renal stones in the lower pole are often difficult to treat. The angle of the lower pole to the renal pelvis (lower pole angle) is a limiting factor to rendering the patient stone free. This review explores the definitions of the lower pole angle, the various treatment options available, and how outcomes are influenced by the angle. RECENT FINDINGS: It is clear the lower pole angle definition varies widely depending on described technique and imaging modality. However, it is clear that outcomes are worse with a steeper angle, especially for shock wave lithotripsy and retrograde intrarenal surgery (RIRS). Percutaneous nephrolithotomy has similar reported outcomes to RIRS, and there is limited evidence it may be superior for steeper angles over RIRS. Lower pole stones can be technically challenging and adequate assessment prior to choosing operative approach is key.

Outcomes of Paediatric Cystine Stone Management: Results of a Systematic Review.

PURPOSE OF REVIEW: We wanted to analyse the outcomes of surgical (SWL, URS, PCNL) and medical management of cystine stones in the paediatric population in terms of stone-free status and complication rates, based on all the available literature evidence. RECENT FINDINGS: A systematic review of literature was performed for all studies with paediatric cystine stone management. Twelve studies met the eligibility criteria, of which 4 analysed outcomes of SWL, 2 of URS and 3 of PCNL and 3 focused on the effect of either alkalising agents (potassium citrate, citric acid) or cysteine-binding thiol (CBT) agents (tiopronin, penicillamine). The reported SFR in studies ranged from 50 to 83%, 59 to 100% and 63 to 80.6%, with a complication rate of 2.8-51%, 14-27% and 12.9-15.4% with SWL, URS and PCNL, respectively. Paediatric cystine stones treatment should aim at complete stone clearance, preservation of renal function and prevention of further recurrences. SWL achieves inferior results in case of cystine stones. URS and PCNL are safe and effective procedures in the paediatric population, with a low rate of major complications. Adherence to medical prevention therapies may prolong recurrence-free periods.

Innovations in Kidney Stone Removal.

Urolithiasis is a common clinical condition, and surgical treatment is performed with different minimally invasive procedures, such as ureteroscopy, shockwave lithotripsy and percutaneous nephrolithotomy. Although the transition from open surgery to endourological procedures to treat this condition has been a paradigm shift, ongoing technological advancements have permitted further improvement of clinical outcomes with the development of modern equipment. Such innovations in kidney stone removal are new lasers, modern ureteroscopes, development of applications and training systems utilizing three-dimensional models, artificial intelligence and virtual reality, implementation of robotic systems, sheaths connected to vacuum devices and new types of lithotripters. Innovations in kidney stone removal have led to an exciting new era of endourological options for patients and clinicians alike.

Enhanced Remdesivir Analogues to Target SARS-CoV-2.

We report the short synthesis of novel C-nucleoside Remdesivir analogues, their cytotoxicity and an in vitro evaluation against SARS-CoV-2 (CoV2). The described compounds are nucleoside analogues bearing a nitrogen heterocycle as purine analogues. The hybrid structures described herein are designed to enhance the anti-CoV2 activity of Remdesivir. The compounds were evaluated for their cytotoxicity and their anti-CoV2 effect. We discuss the impact of combining both sugar and base modifications on the biological activities of these compounds, their lack of cytotoxicity and their antiviral efficacy.

Viral Nucleases.

Nucleases are ubiquitous hydrolytic enzymes that cleave phosphodiester bond of DNA (DNases), RNA (RNases), or protein-RNA/DNA (phosphodiesterases), within the strand (endonucleases) or from the end (exonucleases) [...].