Advancing the field of viroporins-Structure, function and pharmacology: IUPHAR Review 39.

Viroporins possess important potential as antiviral targets due to their critical roles during virus life cycles, spanning from virus entry to egress. Although the antiviral amantadine targets the M2 viroporin of influenza A virus, successful progression of other viroporin inhibitors into clinical use remains challenging. These challenges relate in varying proportions to a lack of reliable full-length 3D-structures, difficulties in functionally characterising individual viroporins, and absence of verifiable direct binding between inhibitor and viroporin. This review offers perspectives to help overcome these challenges. We provide a comprehensive overview of the viroporin family, including their structural and functional features, highlighting the moldability of their energy landscapes and actions. To advance the field, we suggest a list of best practices to aspire towards unambiguous viroporin identification and characterisation, along with considerations of potential pitfalls. Finally, we present current and future scenarios of, and prospects for, viroporin targeting drugs.

Inhibitors of the small membrane (M) protein viroporin prevent Zika virus infection.

Flaviviruses, including Zika virus (ZIKV), are a significant global health concern, yet no licensed antivirals exist to treat disease. The small membrane (M) protein plays well-defined roles during viral egress and remains within virion membranes following release and maturation. However, it is unclear whether M plays a functional role in this setting. Here, we show that M forms oligomeric membrane-permeabilising channels in vitro, with increased activity at acidic pH and sensitivity to the prototypic channel-blocker, rimantadine. Accordingly, rimantadine blocked an early stage of ZIKV cell culture infection. Structure-based channel models, comprising hexameric arrangements of two trans-membrane domain protomers were shown to comprise more stable assemblages than other oligomers using molecular dynamics simulations. Models contained a predicted lumenal rimantadine-binding site, as well as a second druggable target region on the membrane-exposed periphery. In silico screening enriched for repurposed drugs/compounds predicted to bind to either one site or the other. Hits displayed superior potency in vitro and in cell culture compared with rimantadine, with efficacy demonstrably linked to virion-resident channels. Finally, rimantadine effectively blocked ZIKV viraemia in preclinical models, supporting that M constitutes a physiologically relevant target. This could be explored by repurposing rimantadine, or development of new M-targeted therapies.

A Machine Learning Predictive Model for Ureteroscopy Lasertripsy Outcomes in a Pediatric Population-Results from a Large Endourology Tertiary Center.

Introduction: We aimed to develop machine learning (ML) algorithms for the automated prediction of postoperative ureteroscopy outcomes for pediatric kidney stones based on preoperative characteristics. Materials and Methods: Data from pediatric patients who underwent ureteroscopy for stone treatment by a single experienced surgeon, between 2010 and 2023 in Southampton General Hospital, were retrospectively collected. Fifteen ML classification algorithms were used to investigate correlations between preoperative characteristics and postoperative outcomes: primary stone-free status (SFS, defined as stone fragments <2 mm at the end of the procedure confirmed endoscopically and no evidence of stone fragments >2 mm at Xray kidney-ureters-bladder (XR KUB) or ultrasound kidney-ureters-bladder (US KUB) at 3 months follow-up) and complications. For the task of complication and stone status, an ensemble model was made out of Bagging classifier, Extra Trees classifier, and linear discriminant analysis. Also, a multitask neural network was constructed for the simultaneous prediction of all postoperative characteristics. Finally, explainable artificial intelligence techniques were used to explain the prediction made by the best models. Results: The ensemble model produced the highest accuracy (90%) in predicting SFS, finding correlation with overall stone size (-0.205), presence of multiple stones (-0.127), and preoperative stenting (-0.102). Complications were predicted by Synthetic Minority Oversampling Technique (SMOTE) oversampled dataset (93.3% accuracy) with relation to preoperative positive urine culture (-0.060) a1nd SFS (0.003). Training ML for the multitask model, accuracies of 83.3% and 80% were respectively reached. Conclusion: ML has a great potential of assisting health care research, with possibilities to investigate dataset at a higher level. With the aid of this intelligent tool, urologists can implement their practice and develop new strategies for outcome prediction and patient counseling and informed shared decision-making. Our model reached an excellent accuracy in predicting SFS and complications in the pediatric population, leading the way to the validation of patient-specific predictive tools.

First worldwide report on safety and efficacy of using small 7.5 Fr scope for pediatric ureteroscopy: prospective pilot series from Europe.

Introduction: Although pediatric urolithiasis remains relatively uncommon, its global prevalence is on the rise. Technological advances have led to miniaturization of instruments especially in the form of single use scopes. As the evidence on the use of small single use ureteroscopes in children is scarce, we have conducted a pilot two-center study to analyze the outcomes of pediatric patients treated with the Pusen 7.5 Fr single use scopes at our institutions. Material and methods: This study included consecutive pediatric patients with urinary stones treated with the small Pusen 7.5 Fr single use ureteroscope. The study was conducted at two large European tertiary endourology centers that specialize in pediatric kidney stone management. Patient data and outcomes were prospectively collected, and analysis was performed regarding patient demographics, stone parameters, as well as stone free rate (SFR), operating time, and complications. Results: In this pilot study, 26 patients were included with a median age of 12 years (7.0-16.0) and a male to female ratio of 14:12. The mean cumulative stone size was 15.15 mm (SD ±11.1) and multiple stones were present in 9 (34.6%) patients. Pre-operative stent, access sheath and post-operative stent usage was done in 12 (46.2%), 23 (88.5%) and 13 (50%) patients respectively. The median operative time was 47 minutes (IQR: 40.0-63.8). Following the initial procedure 24 (92.3%) patients were stone free, while no intra or postoperative complications were observed. Conclusions: Our study demonstrates that the use of the small 7.5 single use ureteroscope is safe and efficient for the treatment of urinary stones in pediatric patients with high stone-free rates and no complications noted in our series. While this might become a standard of care in future, to confirm and validate our findings further studies with larger cohorts are warranted.

The Utility and Safety of Ureteral Access Sheath During Retrograde Intrarenal Surgery in Children.

OBJECTIVE: To compare retrograde intrarenal surgery (RIRS) with and without ureteral access sheath (UAS) in different pediatric age groups. METHODS: The data of RIRS for kidney stone in children were obtained from 9 institutions. Demographic characteristics of patients and stones, intraoperative and postoperative results were recorded. While analyzing the data, patients who underwent RIRS without UAS (group 1) (n = 195) and RIRS with UAS (group 2) (n = 194) were compared. RESULTS: Group 1 was found to be young, thin, and short (P <.001, P = .021, P <.001), but there was no gender difference and similar symptoms were present except hematuria, which was predominant in group 2 (10.6% vs 17.3%, P <.001). Group 1 had smaller stone diameter (9.91 ± 4.46 vs 11.59 ± 4.85 mm, P = .001), shorter operation time (P = .040), less stenting (35.7% vs 72.7%, P = .003). Re-intervention rates and stone-free rates (SFR) were similar between groups (P = .5 and P = .374). However, group 1 had significantly high re-RIRS (P = .009). SFR had a positive correlation with smaller stone size and thulium fiber laser usage compared to holmium fiber laser (HFL) (P <.001 and P = .020), but multivariate analysis revealed only large stone size as a risk factor for residual fragments (P = .001). CONCLUSION: RIRS can be performed safely in children with and without UAS. In children of smaller size or younger age (<5 years), limited use of UAS was observed. UAS may be of greater utility in stones larger than 1 cm, regardless of the age, and using smaller diameter UAS and ureteroscopes can decrease the complications.

Safety and Efficacy of "Dusting and Pop-Dusting" with High-Power Laser for Treatment of Large Pediatric Stones with Ureteroscopy and Lasertripsy: Prospective Outcomes from a University Teaching Hospital.

Introduction: The wide use of high-power laser has changed the landscape of ureteroscopy and lasertripsy (URSL). We wanted to look at the role and outcomes of high-power holmium:yttrium-aluminum-garnet laser for URSL in pediatric stone disease. Methods: A prospective analysis of consecutive pediatric patients treated with "Dusting and Pop-dusting" using a high-power laser was done between January 2016 and March 2022. The project was registered with our audit committee. Data were analyzed for patient demographics, stone characteristics, operative details, procedural outcomes, and complications. Stone-free rate (SFR) was defined as fragments ≤2 mm on postoperative ultrasound imaging 2-3 months after the procedure. Results: A total of 35 patients underwent 43 procedures (1.2 procedure/patient) during the study period with a mean age of 9.4 years (range 1-16 years) and a male:female ratio of 13:22. The stone location was in the kidney in 32 (91.4%) patients of which 8 were in multiple renal locations. The mean stone size was 18 mm (range 10-39 mm), with the pre- and post-stent rates of 37% and 56%, respectively. An access sheath was used in 19 (44%) procedures. The overall SFR on ultrasound scan was 94% (n = 33) with no procedural complications noted in our series and a mean length of stay of 0.9 days. Conclusion: Pediatric URSL using a high-power laser achieves a high SFR even for large and multiple renal stones with no complications noted in our prospective series. Parents must, however, be counseled about the need for staged procedures, which might be needed for large stones.

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.

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.

Comparison of Low-Power vs High-Power Holmium Lasers in Pediatric Retrograde Intrarenal Surgery Outcomes.

Objectives: To compare the outcomes of using low-power (up to 30 W) vs high-power (up to 120 W) holmium lasers in retrograde intrarenal surgery (RIRS) in children and to analyze if lasering techniques and the use of access sheath have any influence on the outcomes. Methods: We retrospectively reviewed data from 9 centers of children who underwent RIRS with holmium laser for the treatment of kidney stones between January 2015 and December 2020. Patients were divided into two groups: high-power and low-power holmium laser. Clinical, perioperative variables and complications were analyzed. Outcomes were compared between groups using Student's t-test for continuous variables, and Chi-square and Fisher's exact test for categorical variables. A multivariable logistic regression analysis model was also performed. Results: A total of 314 patients were included. A high-power and low-power holmium laser was used in 97 and 217 patients, respectively. Clinical and demographic variables were comparable between both groups, except for stone size where the low-power group treated larger stones (mean 11.11 vs 9.70 mm, p = 0.018). In the high-power laser group, a reduction in surgical time was found (mean 64.29 vs 75.27 minutes, p = 0.018) with a significantly higher stone-free rate (SFR) (mean 81.4% vs 59%, p < 0.001). We found no statistical differences in complication rates. The multivariate logistic regression model showed lower SFR in the low-power holmium group, especially with larger (p = 0.011) and multiple stones (p < 0.001). Conclusion: Our real-world pediatric multicenter study favors high-power holmium laser and establishes its safety and efficacy in children.

Comparison and Evaluation of Outcomes of Ureteroscopy and Stone Laser Fragmentation in Extremes of Age Groups (≤10 Years and ≥80 Years of Age): A Retrospective Comparative Analysis of over 15 Years from 2 Tertiary European Centres.

AIM: To assess and compare the outcomes associated with ureteroscopy and laser fragmentation (URSL) for extremes of age group (≤10 and ≥80 years). METHODS: Retrospective consecutive data were collected from two European centres for all paediatric patients ≤10 undergoing URSL over a 15-year period (group 1). It was compared to consecutive data for all patients ≥80 years (group 2). Data were collected for patient demographics, stone characteristics, operative details, and clinical outcomes. RESULTS: A total of 168 patients had 201 URSL procedures during this time (74 and 94 patients in groups 1 and 2 respectively). The mean age and stone sizes were 6.1 years and 85 years, and 9.7 mm and 13 mm for groups 1 and 2 respectively. While the SFR was slightly higher in group 2 (92.5% versus 87.8%, p = 0.301), post-operative stent rate was also significantly higher in the geriatric population (75.9% versus 41.2%, p = 0.0001). There was also no significant difference in pre-operative stenting (p = 0.886), ureteric access sheath use (UAS) (p = 0.220) and post-operative complications. Group 1 had an intervention rate of 1.3/patient as compared to 1.1/patient in group 2. The overall complications were 7.2% and 15.3% in groups 1 and 2 respectively (0.069), with 1 Clavien IV complication related to post-operative sepsis and brief ICU admission in group 2. CONCLUSION: The paediatric population had a marginally higher incidence of repeat procedure, but the overall SFR and complications were similar, and post-operative stent insertion rates were much better compared to geriatric patients. URSL is a safe procedure in the extremes of age groups with no difference in the overall outcomes between the two groups.

Role of Preoperative Ureteral Stent on Outcomes of Retrograde Intra-Renal Surgery (RIRS) in Children. Results From a Comparative, Large, Multicenter Series.

OBJECTIVE: To assess outcomes of pre-stenting versus non-pre-stenting in children undergoing retrograde intrarenal surgery (RIRS) for intrarenal stones. METHODS: Children/adolescent with kidney stones undergoing RIRS in 9 centers between 2015 and 2020 were retrospectively reviewed. EXCLUSION CRITERIA: ureteral lithotripsy, bilateral procedures. Stone-free status was evaluated at 3-month and defined as a single residual fragment (RF) ≤2 mm/absence of multiple fragments. Patients were divided into two groups (Group 1 no-prestenting; Group 2 prestenting). Student's, Chi-square and Fisher's exact test was used to assess difference between groups. Univariable and multivariable logistic regression analysis were performed to predict RF. Statistical significance: P-value <0.05. RESULTS: Three hundred eighty-nine children/adolescents were included (192 patients in Group 1). Prestented patients were younger compared with non-prestented (mean age 8.30 ± 4.93 vs 10.43 ± 4.30 years, P < 0.001). There were no differences in stone characteristics (number, size, locations). Lasing and total surgical time were similar. Urinary tract infections were more prevalent in Group 2 (10.7%) compared to Group 1 (3.7%, P = 0.016). Sepsis occurred in 2.1% of patients in Group 2 and no patient in Group 1 (P = 0.146). 30.7% patients in Group 1 and 26.4% in Group 2 had RF (P = 0.322). In univariate logistic regression analysis, stone size was associated with RF (OR 1.12 95%CI 1.06-1.18, P < 0.001), whereas Thulium fiber laser with a lower incidence (OR 0.24 95%CI 0.06-0.69, p=0.020). Multivariate logistic regression analysis showed that stone size was associated with RF (OR 1.20 95%CI 1.08-1.36, P = 0.001). CONCLUSIONS: RIRS showed similar stone-free rate in pre and non-prestented children/adolescents, although prestented patients were younger. A higher risk of post-operative infections was reported in prestented patients.

SKIPping With PALS: Exploring Parental Engagement in a Motor Intervention for Their Preschool Children.

Purpose: The purpose of this study was to explore how parent involvement influenced the effectiveness of a movement intervention targeting gross motor skills and physical activity behavior in preschool-aged boys and girls. Methods: Parents received training at monthly school-based sessions and online to implement the movement intervention once per month at school and once per week at home across 6 months (N = 104; Mage = 48.30 months, SD = 6.90). Children completed the Test of Gross Motor Development-3 at baseline and wore physical activity trackers 24/7 for six weeks during the intervention. COVID-19 disrupted the intervention and prevented immediate post testing. Children (N = 60; Mage = 60.86 months, SD = 6.57) who returned to the center one year later completed gross motor skill retention testing. Results: For each additional school-based session attended by the parents (up to six), children's locomotor and manipulative skills were 1.87 and 1.95 points higher, respectively, at the start of the following academic year. For physical activity, each session increase in attendance at the school-based component of the intervention resulted in an additional 1455 steps in average weekly step count. Conclusion: Increased parent engagement demonstrated greater change in gross motor skills and larger acute physical activity responses. Understanding barriers that impact the level of parental intervention engagement (i.e., dose) also provides insight into why some children learn and others do not within a parent-led intervention. Although the implementation and results of this study were impacted by COVID, these data can help researchers optimize future intervention strategies.

Outcomes of ureteroscopy for management of stone disease in early and late childhood over a 15-year period.

Background: Although paediatric ureteroscopy is widely performed, there is still a lack of data and outcomes in early childhood. In this two-centre study, we compared the outcomes of ureteroscopy for stone disease management in early and late childhood and provide outcomes for the same. Methods: Data was retrospectively collected on consecutive patients from two tertiary paediatric endo-urology European centres over a 15-year period (2006-2021). Patients were split into two groups, namely, early childhood (age ⩽ 9 years) and late childhood (age 9 to ⩽16 years). Outcomes including stone-free rate (SFR) and complications were compared between these two groups. Results: A total of 148 patients underwent 184 procedures (1.2 procedure/patient) during the study period (66 in early childhood and 82 in late childhood). The mean age in early and late childhood groups were 5.6 and 13.3 years, and a male: female ratio of 1.6:1 and 1.1:1, respectively. The SFR and complications in early and late childhood groups were 87.8% and 90.2% (p = 0.64) and 5.7% and 4.1%, respectively. Conclusion: Paediatric ureteroscopy and laser stone fragmentation achieves good results in both early and late childhood with comparable SFRs, although the complications and need for second procedure were marginally higher in the early childhood group. Our study would set up a new benchmark for patient counselling in future, and perhaps this needs to be reflected in the paediatric urolithiasis guidelines.

Role of Pediatric Ureteral Access Sheath and Outcomes Related to Flexible Ureteroscopy and Laser Stone Fragmentation: A Systematic Review of Literature.

Context: Flexible ureteroscopy and laser lithotripsy (FURSL) represent a good treatment option for pediatric urolithiasis. Scarce evidence is available about the safety and efficacy of the concomitant use of a ureteral access sheath (UAS) in the setting of pediatric ureteroscopy (URS). Objective: To acquire all the available evidence on UAS usage in pediatric FURSL, focusing on intra- and postoperative complications and stone-free rates (SFRs). Evidence acquisition: We performed a systematic literature research using PubMed/MEDLINE, Embase, and Scopus databases. The inclusion criteria were cohorts of pediatric patients <18 yr old, submitted to URS for FURSL, reporting on more than ten cases of UAS placement. The primary outcomes were prestenting rates, operating time, ureteric stent placement rates after surgery, rates and grades of complications, ureteral injuries, and overall SFR. A total of 22 articles were selected. Evidence synthesis: In total, 26 intraoperative and 130 postoperative complications following URS with UAS placement were reported (1.8% and 9.18% of the overall procedures, respectively). According to the Clavien-Dindo classification, 32 were classified as Clavien I, 29 as Clavien II, 43 as Clavien I or II, six as Clavien III, and one as Clavien IV. Twenty-one cases of ureteral injuries (1.59%) were noted in the whole cohort; most of them were ureteral perforation or extravasation, and were treated with a temporary indwelling ureteric stent. The overall SFR after a single URS procedure was 76.92%; after at least a second procedure, it was 84.9%. Conclusions: FURSL is a safe and effective treatment option for pediatric urolithiasis. UAS use was associated with a low rate of ureteric injuries, mostly treated and resolved with a temporary indwelling ureteric stent. Patient summary: We performed a systematic literature research on the utilization of a UAS during ureteroscopy for stone treatment in pediatric patients. We assessed the outcomes related to the rates of intra- and postoperative complications and the rates of efficacy of the procedure in the clearance of stones. The evidence shows a low rate and grade of complications associated with UAS placement and good stone-free outcomes. A ureteric injury may occur in 1.6% of cases, but it is usually managed and resolved with a temporary indwelling ureteric stent.

Mosquito saliva enhances virus infection through sialokinin-dependent vascular leakage.

Viruses transmitted by Aedes mosquitoes are an increasingly important global cause of disease. Defining common determinants of host susceptibility to this large group of heterogenous pathogens is key for informing the rational design of panviral medicines. Infection of the vertebrate host with these viruses is enhanced by mosquito saliva, a complex mixture of salivary-gland-derived factors and microbiota. We show that the enhancement of infection by saliva was dependent on vascular function and was independent of most antisaliva immune responses, including salivary microbiota. Instead, the Aedes gene product sialokinin mediated the enhancement of virus infection through a rapid reduction in endothelial barrier integrity. Sialokinin is unique within the insect world as having a vertebrate-like tachykinin sequence and is absent from Anopheles mosquitoes, which are incompetent for most arthropod-borne viruses, whose saliva was not proviral and did not induce similar vascular permeability. Therapeutic strategies targeting sialokinin have the potential to limit disease severity following infection with Aedes-mosquito-borne viruses.

Outcomes and lessons learnt from practice of retrograde intrarenal surgery (RIRS) in a paediatric setting of various age groups: a global study across 8 centres.

PURPOSE: To analyse and report the practice, outcomes and lessons learnt from a global series of retrograde intrarenal surgery (RIRS) in a paediatric multicentre series. METHODS: A retrospective review of anonymized pooled data gathered globally from 8 centres in paediatric patients (≤ 18 years of age) who had renal stones and underwent RIRS from 2015 to 2020 was performed. Patient demographics, perioperative parameters, stone characteristics, complications and stone-free rate (SFR; defined as endoscopically stone free and/or residual fragments < 2 mm on follow up imaging) were analysed. The cohort was stratified into 3 groups by age: < 5 years (Group A), 5-10 years (Group B) and > 10 years (Group C). Overall, post-operative complication rate was 13.7%. Chi-square comparisons were used for categorical variables; analysis of variance (ANOVA) or Kruskal-Wallis tests were used for continuous variables. RESULTS: 314 patients were analysed. The mean age was 9.54 ± 4.76 years. Groups A, B and C had 67 (21.3%), 83 (26.4%) and 164 (52.2%) patients, respectively. Mean stone size was 10.7 ± 4.62 mm. Pre-stenting was performed in 155 (49.4%) of patients, ureteral access sheaths (UAS) was used in 54.5% of patients with majority (71%) utilizing holmium laser for stone fragmentation. All complications were minor (Clavien-Dindo grade 1 and 2). SFR was 75.5%. CONCLUSIONS: RIRS is acceptable as a first-line intervention in the paediatric population with reasonable efficacy and low morbidity. Complications are slightly higher in patients < 5 years of age, which should be taken into account while counselling patients.

10-year experience of Paediatric varicocele embolization in a tertiary centre with long-term follow-up.

INTRODUCTION: Paediatric varicocele embolization has many benefits over surgical ligation, but lacks published long-term data. We investigated technical and clinical outcomes in this under reported patient group. OBJECTIVE: To evaluate technical success, complications and recurrence rates following varicocele embolization in paediatric patients. MATERIALS AND METHODS: A single-centre retrospective review of procedural data and electronic notes of consecutive patients referred for varicocele embolization over a 10-year period was performed (February 2010-March 2020). The primary outcomes were technical success and clinical efficacy (lack of symptom recurrence). Secondary outcomes included complications, testicular vein size reduction and procedural parameters including radiation exposure. Chi-square analysis was used to identify predictors of clinical success. Follow-up involved outpatient clinical assessment and telephone interview. RESULTS: 40 patients (median age 15) were referred for left-sided symptomatic varicocele. Technical embolization success was achieved in 36/40 patients (90%), with 4 procedures abandoned (inaccessible vein). Embolization technique was platinum-based coils ± sclerosant. There were no immediate or long-term procedural complications. 32/36 patients completed short term follow-up at a median interval of 2.8 months. 30/32 (93.78%) experienced early clinical success. We found a significant reduction in peritesticular vein size following embolization (pre-3.70 vs post-2.56 mm, p = 0.00017) and a significant relationship between varicocele grade and early clinical success (χ2 = 4.2, p = 0.04), but not pre-treatment peritesticular vein size (χ2 = 0.02, p = 0.88). 33/36 patients completed long-term follow-up (median 4.2 years, range 0.36-9.9 years) producing a late clinical success rate of 93.9% (31/33). No post procedural complications including hydroceles were identified. DISCUSSION: This study demonstrates technical success, matching rates described in adult patients which is reassuring and in support of embolization in the younger patient cohort. More importantly, the overall clinical success rate is comparable with previous embolization studies. Reassuringly, all symptom recurrences occurred early in follow-up, and there is a cogent argument for a single follow-up appointment at this juncture. Our long-term average follow-up duration, primarily gained via telephone interview, exceeds other studies. Although our study has the longest follow-up for varicocele embolization in children, it is limited by a few patients being lost to early and long-term follow-up. This is a recognised issue faced by studies attempting to follow-up benign conditions with a high clinical success rate. CONCLUSION: Paediatric varicocele embolization is a successful alternative to surgical ligation, with no complications and good clinical outcomes over a long-term follow-up.

Vaccinating adolescents against SARS-CoV-2 in England: a risk-benefit analysis.

OBJECTIVE: To offer a quantitative risk-benefit analysis of two doses of SARS-CoV-2 vaccination among adolescents in England. SETTING: England. DESIGN: Following the risk-benefit analysis methodology carried out by the US Centers for Disease Control, we calculated historical rates of hospital admission, Intensive Care Unit admission and death for ascertained SARS-CoV-2 cases in children aged 12-17 in England. We then used these rates alongside a range of estimates for incidence of long COVID, vaccine efficacy and vaccine-induced myocarditis, to estimate hospital and Intensive Care Unit admissions, deaths and cases of long COVID over a period of 16 weeks under assumptions of high and low case incidence. PARTICIPANTS: All 12-17 year olds with a record of confirmed SARS-CoV-2 infection in England between 1 July 2020 and 31 March 2021 using national linked electronic health records, accessed through the British Heart Foundation Data Science Centre. MAIN OUTCOME MEASURES: Hospitalisations, Intensive Care Unit admissions, deaths and cases of long COVID averted by vaccinating all 12-17 year olds in England over a 16-week period under different estimates of future case incidence. RESULTS: At high future case incidence of 1000/100,000 population/week over 16 weeks, vaccination could avert 4430 hospital admissions and 36 deaths over 16 weeks. At the low incidence of 50/100,000/week, vaccination could avert 70 hospital admissions and two deaths over 16 weeks. The benefit of vaccination in terms of hospitalisations in adolescents outweighs risks unless case rates are sustainably very low (below 30/100,000 teenagers/week). Benefit of vaccination exists at any case rate for the outcomes of death and long COVID, since neither have been associated with vaccination to date. CONCLUSIONS: Given the current (as at 15 September 2021) high case rates (680/100,000 population/week in 10-19 year olds) in England, our findings support vaccination of adolescents against SARS-CoV2.

Rapid evidence review to inform safe return to campus in the context of coronavirus disease 2019 (COVID-19).

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted predominantly through the air in crowded and unventilated indoor spaces among unvaccinated people. Universities and colleges are potential settings for its spread. Methods: An interdisciplinary team from public health, virology, and biology used narrative methods to summarise and synthesise evidence on key control measures, taking account of mode of transmission. Results: Evidence from a wide range of primary studies supports six measures.  Vaccinate (aim for > 90% coverage and make it easy to get a jab). Require masks indoors, especially in crowded settings. If everyone wears well-fitting cloth masks, source control will be high, but for maximum self-protection, respirator masks should be worn.  Masks should not be removed for speaking or singing. Space people out by physical distancing (but there is no "safe" distance because transmission risk varies with factors such as ventilation, activity levels and crowding), reducing class size (including offering blended learning), and cohorting (students remain in small groups with no cross-mixing). Clean indoor air using engineering controls-ventilation (while monitoring CO 2 levels), inbuilt filtration systems, or portable air cleaners fitted with high efficiency particulate air [HEPA] filters). Test asymptomatic staff and students using lateral flow tests, with tracing and isolating infectious cases when incidence of coronavirus disease 2019 (COVID-19) is high. Support clinically vulnerable people to work remotely. There is no direct evidence to support hand sanitising, fomite controls or temperature-taking. There is evidence that freestanding plastic screens, face visors and electronic air-cleaning systems are ineffective. Conclusions: The above six evidence-based measures should be combined into a multi-faceted strategy to maximise both student safety and the continuation of in-person and online education provision. Staff and students seeking to negotiate a safe working and learning environment should collect data (e.g. CO 2 levels, room occupancy) to inform conversations.