Next generation sequencing in patients with nephrolithiasis: how does it perform compared with standard urine and stone cultures?

Background: Our aim was to compare microorganism detection between standard culture (Ctx) and next generation sequencing (NGS) in patients undergoing surgery for nephrolithiasis; we prospectively compared both urine and stone culture results using these two techniques. Methods: We prospectively compared microorganism detection of urine and stone cultures using Ctx versus NGS in patients undergoing surgery for nephrolithiasis. We analyzed preoperative voided urine (Voided) using both Ctx and NGS. Intraoperatively, renal stone (Stone) cultures were analyzed with Ctx and NGS. The primary outcome was concordance in microorganism detection between Voided Ctx and Stone NGS, as well as between Stone Ctx and Stone NGS. Results: We prospectively evaluated 84 patients. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of Voided Ctx predicting Stone Ctx were 66.7%, 73.7%, 54.5%, and 82.4%, respectively. Concordance of Voided Ctx microorganisms to Stone microorganisms decreased when NGS was used for the Stone compared with Ctx. The sensitivity, specificity, PPV, and NPV of Voided NGS to predict Stone Ctx microorganisms were 85.2%, 24.6%, 34.8%, and 77.8%, respectively. The concordance of Voided NGS to Stone microorganisms improved when the Stone was analyzed via NGS compared with Ctx. Conclusion: NGS has a higher detection rate of microorganisms than standard culture for both preoperative urine and stone cultures. Voided NGS was the most sensitive in predicting a positive Stone sample, but the specificity and PPV were, overall, low. Further correlation of NGS microorganism detection with patient outcomes will determine which clinical situations may benefit most from NGS versus standard culture in patients with urinary-tract stones

MR fluoroscopy in vascular and cardiac interventions (review)

Vascular and cardiac disease remains a leading cause of morbidity and mortality in developed and emerging countries. Vascular and cardiac interventions require extensive fluoroscopic guidance to navigate endovascular catheters. X-ray fluoroscopy is considered the current modality for real time imaging. It provides excellent spatial and temporal resolution, but is limited by exposure of patients and staff to ionizing radiation, poor soft tissue characterization and lack of quantitative physiologic information. MR fluoroscopy has been introduced with substantial progress during the last decade. Clinical and experimental studies performed under MR fluoroscopy have indicated the suitability of this modality for: delivery of ASD closure, aortic valves, and endovascular stents (aortic, carotid, iliac, renal arteries, inferior vena cava). It aids in performing ablation, creation of hepatic shunts and local delivery of therapies. Development of more MR compatible equipment and devices will widen the applications of MR-guided procedures. At post-intervention, MR imaging aids in assessing the efficacy of therapies, success of interventions. It also provides information on vascular flow and cardiac morphology, function, perfusion and viability. MR fluoroscopy has the potential to form the basis for minimally invasive image–guided surgeries that offer improved patient management and cost effectiveness

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study.

Funder: Action Bladder Cancer UKFunder: Rosetrees Trust; Id: http://dx.doi.org/10.13039/501100000833Funder: Urology Care Foundation; Id: http://dx.doi.org/10.13039/100006280OBJECTIVE: To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. PATIENTS AND METHODS: This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. RESULTS: Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3-34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1-30.2), UTUC (n = 128) 1.14% (95% CI 0.77-1.52), renal cancer (n = 107) 1.05% (95% CI 0.80-1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32-2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03-1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90-4.15; P < 0.001), male sex 1.30 (95% CI 1.14-1.50; P < 0.001), and smoking 2.70 (95% CI 2.30-3.18; P < 0.001). CONCLUSIONS: A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study

Objective To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. Patients and Methods This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. Results Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3–34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1–30.2), UTUC (n = 128) 1.14% (95% CI 0.77–1.52), renal cancer (n = 107) 1.05% (95% CI 0.80–1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32–2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03–1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90–4.15; P < 0.001), male sex 1.30 (95% CI 1.14–1.50; P < 0.001), and smoking 2.70 (95% CI 2.30–3.18; P < 0.001). Conclusions A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer

Understanding holmium laser enucleation of the prostate (HoLEP) recovery: Assessing patient expectations and understanding

Introduction: Although holmium laser enucleation of the prostate (HoLEP) is a highly effective surgery, there is a variable recovery period where patients may experience hematuria, dysuria, or urinary incontinence (UI). Despite preoperative consultation, there is a paucity of literature examining the effectiveness of physician-patient communication in preparing the patient for the postoperative recovery period. We sought to examine recovery expectations as a patient-reported outcome (PRO) metric for HoLEP. Methods: With institutional review board approval, we queried our electronic medical record and retrospective clinical registry to identify 50 consecutive patients that underwent HoLEP from November 2019 to March 2020 by two endourologists. Patients were provided questionnaires via Twistle© ≥6 months postoperatively. Patient demographics and perioperative course was examined in the context of responses. Our primary objective was determining whether patients felt they had a reasonable understanding of the recovery process. Results: We observed a 92% (46/50) response rate, with an average patient age of 69.4 years (range 55-88). Overall, 91.3% (42/46) felt they had a reasonable understanding of the recovery. Additionally, 97.8% (45/46) were aware of temporary UI, with 87% having ≥1 episodes of UI after catheter removal. We found 47.8% (22/46) of patients expected UI to resolve within 30 days, while 8.6% expected >90 days of UI. All patients were aware of the risk of hematuria, with 93.5% (43/46) expecting resolution within 30 days (<7 days: 47.8%; 7-14 days: 28.3%; 15-30 days: 17.4%). Conclusions: Although surgical technique continues to improve HoLEP, ensuring adequate physician-patient communication to optimize expectations is crucial. We report patient understanding of HoLEP recovery and areas for future improvement

Ex Vivo Comparison of Efficiency, Safety, and Surgeon Satisfaction in Four Commercial Morcellators

Introduction Holmium Laser Enucleation of the Prostate (HoLEP) is a size-independent treatment option for the management of benign prostatic hypertrophy. While advancements in laser technology have led to clinical improvements in the enucleation portion of HoLEP, the morcellation aspect of HoLEP is often the rate-limiting step. We sought to compare efficiency and surgeon satisfaction in four commercial morcellators. Methods This was an ex vivo study comparing four commercial morcellators: the Wolf Piranha, the Lumenis VersaCut, the JenaSurgical MultiCut Solo, and the Hawk Morcellator. Four surgeons with significant experience performing HoLEPs participated. Surgeons tested each device to morcellate two different prostate models 1) morcellating as much microwave-cooked chicken breast in 10 minutes and 2) timed morcellation of bull testicles. Surgeons completed subjective surveys after each morcellator trial. Objective outcomes included: morcellation efficiency (g/min morcellated) and aspiration power (time to aspirate 1 L of saline). Means of continuous variables were compared using ANOVA. Categorical variables were compared using chi-square tests. Statistical analyses were performed using SAS 9.4 (2019). Results Comparing subjective outcomes, the Piranha was chosen as the safest morcellator (p=0.0058). The least safe morcellator was thought to be the MultiCut by 75% of surgeons (p=0.046). The Piranha was chosen as the most effective morcellator by 75% of surgeons (p=0.046). Comparing objective parameters between the morcellators, the Piranha had the fastest aspiration time (43.50±10.34 s, p=0.0116). There were no significant differences in morcellation efficiency when using chicken breast (p=0.3096). However, when comparing the morcellation efficiency using bull testicles, the Piranha had the highest efficiency at 39.68±3.57 g/min (p=0.0268). Conclusion In this ex-vivo study comparing four different commercially available morcellators, the Piranha had the highest aspiration power. No significant differences were found in morcellation efficiency using microwave-cooked chicken breast. The Piranha was felt to be the safest and most effective morcellator