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Introduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of low quality. Furthermore, there has been minimal engagement with patient representatives following pelvic exenteration with respect to the empty pelvic syndrome. ‘PelvEx—Beating the empty pelvis syndrome’ aims to engage both patient representatives and healthcare professionals to achieve an international consensus on a core outcome set, pathophysiology and mitigation of the empty pelvis syndrome.Methods and analysis A modified-Delphi approach will be followed with a three-stage study design. First, statements will be longlisted using a recent systematic review, healthcare professional event, patient and public engagement, and Delphi piloting. Second, statements will be shortlisted using up to three rounds of online modified Delphi. Third, statements will be confirmed and instruments for measurable statements selected using a virtual patient-representative consensus meeting, and finally a face-to-face healthcare professional consensus meeting.Ethics and dissemination The University of Southampton Faculty of Medicine ethics committee has approved this protocol, which is registered as a study with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of this study will increase the potential for comparative research to further understanding and prevent the empty pelvis syndrome.Trial registration number NCT05683795.

Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.Setting Prospective, international, multicentre, observational cohort study.Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration number NCT04323644

Objective: The objective of this study was to report the 12-month oncological outcomes for patients with non-muscle-invasive bladder cancer (NMIBC) within the prospective, international COVIDSurg Cancer study., Patients and Methods: Eligible patients were aged ≥18 years and scheduled for elective surgical management of NMIBC with curative intent (transurethral resection of bladder tumour [TURBT] or bladder biopsy) from 21 January to 14 April 2020. The primary outcome was disease recurrence within 12 months of previous elective TURBT/bladder biopsy. Secondary outcomes included disease progression within 12 months of previous elective TURBT/bladder biopsy, site-declared delay to surgery from diagnosis as a consequence of COVID-19 and deviation in standard care due to COVID-19. Comparisons were made to cohorts from the pre-pandemic era., Results: Bladder cancer accounted for 2.2% ( n  = 446) of patients in the COVIDSurg Cancer study, with data contributed by 27 centres across 12 countries internationally. Within this included cohort, 229 patients had NMIBC and 12-month follow-up data available. On application of National Institute for Health and Care Excellence (NICE) criteria, 47.2% were classified as having high-risk disease. Overall disease recurrence and progression rates were 29.3% and 9.7% at 12 months, respectively. In purely high-risk pre-pandemic cohorts, the International Bladder Cancer Group (IBCG) estimates a recurrence rate of 25% at 12 months, and the European Association of Urology (EAU) NMIBC 2021 scoring model estimates a 12-month progression rate of 3.5%. As a consequence of the COVID-19 pandemic, 10.9% of patients had site-declared delay to TURBT/bladder biopsy; 7.4% did not undergo intravesical therapy or had early discontinuation of this; 9.2% did not undergo early repeat resection for high-risk disease; and 18.3% had a delay to cystoscopic follow-up surveillance., Conclusions: This prospective study indicates that there were widespread deviations in usual care for NMIBC during the pandemic and that 12-month oncological outcomes appear to be impaired compared to published pre-pandemic outcomes., Competing Interests: All authors declare no conflict of interest., (© 2024 The Author(s). BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Objectives: To evaluate the carbon footprint of the perioperative transurethral resection of bladder tumour (TURBT) pathway from decision to treat to postoperative discharge, and model potential greenhouse gas (GHG) emissions reduction strategies., Materials and Methods: This process-based attributional cradle-to-grave life-cycle assessment (LCA) of GHG emissions modelled the perioperative TURBT pathway at a hospital in Southwest England. We included travel, energy and water use, all reusable and consumable items, and laundry and equipment sterilisation. Resource use for 30 patients undergoing surgery was recorded to understand average GHG emissions and the inter-case variability. Sensitivity analysis was performed for manufacturing location, pharmaceutical manufacturing carbon-intensity, and theatre list utilisation., Results: The median (interquartile range) perioperative TURBT carbon footprint was 131.8 (119.8-153.6) kg of carbon dioxide equivalent. Major pathway categories contributing to GHG emissions were surgical equipment (22.2%), travel (18.6%), gas and electricity (13.3%), and anaesthesia/drugs and associated adjuncts (27.0%), primarily due to consumable items and processes. Readily modifiable GHG emissions hotspots included patient travel for preoperative assessment, glove use, catheter use, irrigation delivery and extraction, and mitomycin C disposal. GHG emissions were higher for those admitted as inpatients after surgery., Conclusions: This cradle-to-grave LCA found multiple modifiable GHG emissions hotspots. Key mitigation themes include minimising avoidable patient travel, rationalising equipment use, optimally filling operating theatre lists, and safely avoiding postoperative catheterisation and hospital admission where possible. A crucial next step is to design and deliver an implementation strategy for the environmentally sustainable changes demonstrated herein., (© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

An urgent need for societal transformation exists to reduce the environmental impact of humanity, because environmental health affects human health. Health care causes ~5% of global greenhouse gas emissions and other substantial and ongoing environmental harms. Thus, health-care professionals and managers must lead ongoing efforts to improve the environmental performance of health systems. Life-cycle assessment (LCA) is a methodology that enables estimation of environmental impacts of products and processes. It models environmental effects from 'cradle' (raw material extraction) to 'grave' (end of useful life) and conventionally reports a range of different impact categories. LCA is a valuable tool when used appropriately. Maximizing its utility requires rational assumptions alongside careful consideration of system boundaries and data sources. Well-executed LCAs are detailed and transparently reported, enabling findings to be adapted or generalized to different settings. Attention should be given to modelling mitigation solutions in LCAs. This important step can guide health-care systems towards new and innovative solutions that embed progress towards international climate agreements. Many urological conditions are common, recurrent or chronic, requiring resource-intensive management with large associated environmental impacts. LCAs in urology have predominantly focussed on greenhouse gas emissions and have enabled identification of modifiable 'hotspots' including electricity use, travel, single-use items, irrigation, reprocessing and waste incineration. However, the methodological and reporting quality of published urology LCAs generally requires improvement and standardization. Health-care evaluation and commissioning frameworks that value LCA findings alongside clinical outcomes and cost could accelerate sustainable innovations. Rapid implementation strategies for known environmentally sustainable solutions are also needed., (© 2024. Springer Nature Limited.)

The Getting It Right First Time (GIRFT) programme is a quality improvement initiative covering the National Health Service in England. The programme aims to standardise clinical practices and improve patient and system level outcomes by utilising data-driven insights and clinically-led recommendations. There are GIRFT workstreams for every medical and surgical specialty, including urology. Defining features of the GIRFT methodology are that it is clinically led by experienced clinicians, data-driven, and specialty specific. Each specialty workstream conducts deep-dive visits to every hospital, analysing performance data and engaging with clinicians and management to identify and share improvement priorities. For urology, GIRFT has completed deep-dive visits and published reports outlining priority areas for development. Reports include recommendations pertaining to streamlining care pathways, reducing the acuity of care environments, enhancing emergency services, optimising utilisation of outpatient services, and workforce training and utilisation. The GIRFT academy provides guides for implementing best practices specific to priority areas of care. These include important disease pathways, and GIRFT-advocated innovations such as urology investigation units and urology area networks. GIRFT offers clinical transformation, cost reduction, equity in access to care, and leaner models of care that are often more environmentally sustainable. Evaluation efforts of the programme have focussed on assessing the adoption of GIRFT recommendations, understanding barriers to change, and modelling the climate impact of advocated practices., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Magnetic resonance imaging (MRI) of the prostate is a new, more accurate, non-invasive test for prostate cancer diagnosis., Aim: To understand the acceptability of MRI for patients and GPs for prostate cancer diagnosis., Design and Setting: Qualitative study of men who had undergone a prostate MRI for possible prostate cancer, and GPs who had referred at least one man for possible prostate cancer in the previous 12 months in West London and Devon., Method: Semi-structured interviews, conducted in person or via telephone, were audio-recorded and transcribed verbatim. Deductive thematic analysis was undertaken using Sekhon's Theoretical Framework of Acceptability, retrospectively for patients and prospectively for GPs., Results: Twenty-two men (12 from Devon, age range 47-80 years), two patients' partners, and 10 GPs (6 female, age range 36-55 years) were interviewed. Prostate MRI was broadly acceptable for most patient participants, and they reported that it was not a significant undertaking to complete the scan. GPs were more varied in their views on prostate MRI, with a broad spectrum of knowledge and understanding of prostate MRI. Some GPs expressed concerns about additional clinical responsibility and local availability of MRI if direct access to prostate MRI in primary care were to be introduced., Conclusion: Prostate MRI appears to be acceptable to patients. Some differences were found between patients in London and Devon, mainly around burden of testing and opportunity costs. Further exploration of GPs' knowledge and understanding of prostate MRI could inform future initiatives to widen access to diagnostic testing in primary care., (© The Authors.)

Objectives: To describe the contemporary evolution of day-case bladder outflow obstruction (BOO) surgery in England and to profile day-case BOO surgery practices across England in terms of the types of operation performed and their safety profiles., Materials and Methods: This was a retrospective observational analysis of Hospital Episode Statistics and UK Office for National Statistics data. All 111 043 recorded operations across 117 hospital trusts over 66 months, from 1 January 2017 to 30 June 2022, were obtained. Operations were identified as one of: transurethral resection of prostate (TURP); laser ablation or enucleation; vapour therapy; prostatic urethral lift (PUL); or bladder neck incision. Monthly day-case rate trends were plotted across the study period. Descriptive data, day-case rates and 30-day hospital readmissions were analysed for each operation type. Multilevel regression modelling with mixed effects was performed to determine whether day-case surgery was associated with higher 30-day hospital readmissions., Results: Day-case patients were younger, with fewer comorbidities. Time series analysis showed a linear day-case rate increase from 8.3% (January 2017) to 21.0% (June 2022). Day-case rates improved for 92/117 trusts in 2021/2022 compared with 2017. Three of the six trusts with the highest day-case rates performed predominantly day-case TURP, and the other three laser surgery. Nationally, PUL and vapour surgery had the highest day-case rates (80.9% and 38.1%). Most inpatient operations were TURP. Multilevel regression modelling found reduced odds of 30-day readmission after day-case BOO surgery (all operations pooled), no difference for day-case vs inpatient TURP, and reduced odds following day-case LASER operations., Conclusions: The day-case rates for BOO surgery have linearly increased. Minimally invasive surgical technologies are commonly performed as day cases, whereas high day-case rates for TURP and for laser ablation operations are seen in a minority of hospitals. Day-case pathways to treat BOO can be safely developed irrespective of operative modality., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Using devices with microfluidic channels can allow for precise control over liquids flowing through them. Merging flows of immiscible liquids can create emulsions with highly monodispersed microdroplets within a carrier liquid, which are ideal for miniaturised reaction vessels which can be generated with a high throughput of tens of thousands of droplets per second. Control of the size and composition of these droplets is generally performed by controlling the pumping system pushing the liquids into the device; however, this is an indirect manipulation and inadequate if absolute precision is required in the size or composition of the droplets. In this work, we extend the previous development of image-based closed-loop feedback control over microdroplet generation to allow for the control of not only the size of droplets but also the composition by merging two aqueous flows. The feedback allows direct control over the desired parameters of volume and ratio of the two components over a wide range of ratios and outperforms current techniques in terms of monodispersity in volume and composition. This technique is ideal for situations where precise control over droplets is critical, or where a library of droplets of different concentrations but the same volume is required.

Background: Alternative splicing (AS) plays a crucial role in transcriptomic diversity and is a hallmark of cancer that profoundly influences the development and progression of prostate cancer (PCa), a prevalent and potentially life-limiting cancer among men. Accumulating evidence has highlighted the association between AS dysregulation and the onset and progression of PCa. However, a comprehensive and integrative analysis of AS profiles at the event level, utilising data from multiple high-throughput cohorts and evaluating the prognosis of PCa progression, remains lacking and calls for thorough exploration., Results: We identified a differentially expressed retained intron event in ZWINT across three distinct cohorts, encompassing an original array-based dataset profiled by us previously and two RNA sequencing (RNA-seq) datasets. Subsequent in-depth analyses of these RNA-seq datasets revealed  141 altered events, of which 21 demonstrated a significant association with patients' biochemical recurrence-free survival (BCRFS). We formulated an AS event-based prognostic signature, capturing six pivotal events in genes CYP4F12, NFATC4, PIGO, CYP3A5, ALS2CL, and FXYD3. This signature effectively differentiated  high-risk patients diagnosed with PCa, who experienced shorter BCRFS, from their low-risk counterparts. Notably, the signature's predictive power surpassed traditional clinicopathological markers in forecasting 5-year BCRFS, demonstrating robust performance in both internal and external validation sets. Lastly, we constructed a novel nomogram that integrates patients' Gleason scores with pathological tumour stages, demonstrating improved prognostication of BCRFS., Conclusions: Prediction of clinical progression remains elusive in PCa. This research uncovers novel splicing events associated with BCRFS, augmenting existing prognostic tools, thus potentially refining clinical decision-making., (© 2023. The Author(s).)

Introduction: Cisplatin-based neoadjuvant chemotherapy (NAC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC). Cisplatin, however, can induce renal toxicity. Furthermore, RC is an independent risk factor for renal injury, with decreases in estimated glomerular filtration rate (eGFR) of up to 6 mL/min/1.73 m 2 reported at one year postoperatively. Our objective was to evaluate the effect of cisplatin-based NAC and RC on the renal function of patients undergoing both., Methods: We analyzed a multicenter database of patients with MIBC, all of whom received cisplatin-based NAC prior to RC. eGFR values were collected at time points T1 (before NAC), T2 (after NAC but before RC), and T3 (one year post-RC). eGFR and proportion of patients with eGFR <60 ml/min/1.73m 2 (chronic kidney disease [CKD] stage ≥3) were compared between these time points. As all patients in this dataset had received NAC, we identified a retrospective cohort of patients from one institution who had undergone RC during the same time period without NAC for context., Results: We identified 234 patients with available renal function data. From T1 to T3, there was a mean decline in eGFR of 17% (13 mL/min/1.73 m 2 ) in the NAC cohort and an increase in proportion of patients with stage ≥3 CKD from 27% to 50%. The parallel cohort of patients who did not receive NAC was comprised of 236 patients. The mean baseline eGFR in this cohort was lower than in the NAC cohort (66 vs. 75 mL/min/1.73 m 2 ). The mean eGFR decline in this non-NAC cohort from T1 to T3 was 6% (4 mL/min/1.73 m 2 ), and the proportion of those with stage ≥3 CKD increased from 37% to 51%., Conclusions: Administration of NAC prior to RC was associated with a 17% decline in eGFR and a nearly doubled incidence of stage ≥3 CKD at one year after RC. Patients who underwent RC without NAC had a higher rate of stage ≥3 CKD at baseline but appeared to have less renal function loss at one year.

Purpose: While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort., Materials and Methods: We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy. We employed bivariate comparisons and stratified multivariable models to quantify the effect of maximal transurethral resection on pathological findings at cystectomy and survival., Results: Of 785 patients, 579 (74%) underwent maximal transurethral resection. Incomplete transurethral resection was more frequent in patients with more advanced clinical tumor (cT) and nodal (cN) stage ( P < .001 and P < .01, respectively), with more advanced ypT stage at cystectomy and higher rates of positive surgical margins ( P < .01 and P < .05, respectively). In multivariable models, maximal transurethral resection was associated with downstaging at cystectomy (adjusted odds ratio 1.6, 95% CI 1.1-2.5). In Cox proportional hazards analysis, maximal transurethral resection was not associated with overall survival (adjusted HR 0.8, 95% CI 0.6-1.1)., Conclusions: In patients undergoing transurethral resection for muscle-invasive bladder cancer prior to neoadjuvant chemotherapy, maximal resection may improve pathological response at cystectomy. However, the ultimate effects on long-term survival and oncologic outcomes warrant further investigation.

Droplet microfluidics allows one to address the ever-increasing demand to screen large libraries of biological samples. Absorbance spectroscopy complements the golden standard of fluorescence detection by label free target identification and providing more quantifiable data. However, this is limited by speed and sensitivity. In this paper we increase the speed of sorting by including acoustofluidics, achieving sorting rates of target droplets of 1 kHz. We improved the device design for detection of absorbance using fibre-based interrogation of samples with integrated lenses in the microfluidic PDMS device for focusing and collimation of light. This optical improvement reduces the scattering and refraction artefacts, improving the signal quality and sensitivity. The novel design allows us to overcome limitations based on dielectrophoresis sorting, such as droplet size dependency, material and dielectric properties of samples. Our acoustic activated absorbance sorter removes the need for offset dyes or matching oils and sorts about a magnitude faster than current absorbance sorters.

Background: Patient factors associated with urinary tract cancer can be used to risk stratify patients referred with haematuria, prioritising those with a higher risk of cancer for prompt investigation., Objective: To develop a prediction model for urinary tract cancer in patients referred with haematuria., Design, Setting, and Participants: A prospective observational study was conducted in 10 282 patients from 110 hospitals across 26 countries, aged ≥16 yr and referred to secondary care with haematuria. Patients with a known or previous urological malignancy were excluded., Outcome Measurements and Statistical Analysis: The primary outcomes were the presence or absence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC], and renal cancer). Mixed-effect multivariable logistic regression was performed with site and country as random effects and clinically important patient-level candidate predictors, chosen a priori, as fixed effects. Predictors were selected primarily using clinical reasoning, in addition to backward stepwise selection. Calibration and discrimination were calculated, and bootstrap validation was performed to calculate optimism., Results and Limitations: The unadjusted prevalence was 17.2% (n = 1763) for bladder cancer, 1.20% (n = 123) for UTUC, and 1.00% (n = 103) for renal cancer. The final model included predictors of increased risk (visible haematuria, age, smoking history, male sex, and family history) and reduced risk (previous haematuria investigations, urinary tract infection, dysuria/suprapubic pain, anticoagulation, catheter use, and previous pelvic radiotherapy). The area under the receiver operating characteristic curve of the final model was 0.86 (95% confidence interval 0.85-0.87). The model is limited to patients without previous urological malignancy., Conclusions: This cancer prediction model is the first to consider established and novel urinary tract cancer diagnostic markers. It can be used in secondary care for risk stratifying patients and aid the clinician's decision-making process in prioritising patients for investigation., Patient Summary: We have developed a tool that uses a person's characteristics to determine the risk of cancer if that person develops blood in the urine (haematuria). This can be used to help prioritise patients for further investigation., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Cisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin ineligible. The aim of this study was to compare clinical outcomes after ≥ 3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis)., Methods: We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥ 3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN + M0) gem-carbo or gem-cis followed by RC., Results: We included 747 patients treated with gem-carbo (n = 147) or gem-cis (n = 600). Patients treated with gem-carbo had a higher Charlson Comorbidity Index (p = 0.016) and more clinically node-positive disease (32% versus 20%; p = 0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem-carbo and gem-cis (20.7% versus 22.1%; p = 0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR 0.99 [95%CI 0.61-1.59]; p = 0.96), overall survival (OS) (HR 1.20 [95%CI 0.85-1.67]; p = 0.31), or cancer-specific survival (CSS) (HR 1.35 [95%CI 0.93-1.96]; p = 0.11). Median OS of patients treated with gem-carbo and gem-cis was 28.6 months (95%CI 18.1-39.1) and 45.1 months (95%CI 32.7-57.6) (p = 0.18), respectively. Median CSS of patients treated with gem-carbo and gem-cis was 28.8 months (95%CI 9.8-47.8) and 71.0 months (95%CI median not reached) (p = 0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences., Conclusion: Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem-carbo and that survival outcomes seem comparable to gem-cis provided patients are able to receive ≥ 3 cycles and undergo RC., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Prostate cancer (PCa) is the second most common male cancer worldwide, but effective biomarkers for the presence or progression risk of disease are currently elusive. In a series of nine matched histologically confirmed PCa and benign samples, we carried out an integrated transcriptome-wide gene expression analysis, including differential gene expression analysis and weighted gene co-expression network analysis (WGCNA), which identified a set of potential gene markers highly associated with tumour status (malignant vs . benign). We then used these genes to establish a minimal progression-free survival (PFS)-associated gene signature (GS) ( PCBP1 , PABPN1 , PTPRF , DANCR , and MYC ) using least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox regression analyses from The Cancer Genome Atlas prostate adenocarcinoma (TCGA-PRAD) dataset. Our signature was able to predict PFS over 1, 3, and 5 years in TCGA-PRAD dataset, with area under the curve (AUC) of 0.64-0.78, and our signature remained as a prognostic factor independent of age, Gleason score, and pathological T and N stages. A nomogram combining the signature and Gleason score demonstrated improved predictive capability for PFS (AUC: 0.71-0.85) and was superior to the Cambridge Prognostic Group (CPG) model alone and some conventionally used clinicopathological factors in predicting PFS. In conclusion, we have identified and validated a novel five-gene signature and established a nomogram that effectively predicted PFS in patients with PCa. Findings may improve current prognosis tools for PFS and contribute to clinical decision-making in PCa treatment., Competing Interests: LH is founder, director and chief scientific officer of SENISCA Ltd. SENISCA’s commercial activities have no bearing on the content of this publication. 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 © 2022 Mou, Spencer, Knight, John, McCullagh, McGrath and Harries.)

Purpose: Enhanced recovery after surgery (ERAS) protocols have been implemented across a variety of disciplines to improve outcomes. Herein we describe the impact of ERAS on quality of life (QOL) and cost for patients undergoing urologic oncology surgery., Methods: A systematic literature search using the MEDLINE, Scopus, Clinictrials.gov, and Cochrane Review databases for studies published between 1946 and 2020 was conducted. Articles were reviewed and assigned a risk of bias by two authors and were included if they addressed ERAS and either QOL or cost-effectiveness for patients undergoing urologic oncology surgery., Results: The literature search yielded a total of 682 studies after removing duplicates, of which 10 (1.5%) were included in the review. Nine articles addressed radical cystectomy, while one addressed ERAS and QOL for laparoscopic nephrectomy. Six publications assessed the impact of ERAS on QOL domains. Questionnaires used for assessment of QOL varied across studies, and timing of administration was heterogeneous. Overall, ERAS improved patient QOL during early phases of recovery within the realms of bowel function, physical/social/cognitive functioning, sleep and pain control. Costs were assessed in 4 retrospective studies including 3 conducted in the United States and one from China all addressing radical cystectomy. Studies demonstrated either decreased costs associated with ERAS as a result of decreased length of stay or no change in cost based on ERAS implementation., Conclusion: While limited studies are published on the subject, ERAS implementation for radical cystectomy and laparoscopic nephrectomy improved patient-reported QOL during early phases of recovery. For radical cystectomy, there was a decreased or neutral overall financial cost associated with ERAS. Further studies assessing QOL and cost-effectiveness over the entire global period of care in a variety of urologic oncology surgeries are warranted., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To determine the preoperative assessment and perioperative outcomes of men undergoing bladder outlet obstruction (BOO) surgery in the UK., Patients and Methods: A retrospective cohort study was conducted of all men undergoing BOO surgery in 105 UK hospitals over a 1-month period. The study included 1456 men, of whom 42% were catheter dependent prior to undergoing surgery., Results: There was no evidence that a frequency-volume chart or urinary symptom questionnaire had been completed in 73% or 50% of men, respectively in the non-catheter-dependent group. Bipolar transurethral resection of the prostate (TURP) was the most common BOO surgical procedure performed (38%). Monopolar TURP was the next most prevalent modality (23%); however, minimally invasive BOO surgical procedures combined accounted for 17% of all procedures performed. Of the cohort 5% of men had complications within 30 days of surgery, only 1% had Clavien-Dindo Grade ≥III complications. Less than 1% of the cohort received a blood transfusion after BOO surgery and 2% were re-admitted to hospital after their BOO surgery. In total only 4% of the whole cohort were catheter dependent after BOO surgery. Pre- and postoperative paired International Prostate Symptom Score scores reviewed suggest that minimally invasive surgical procedures achieved comparable levels of improvement in both symptoms and bother at 3 months postoperatively in men who were not catheter dependent preoperatively., Conclusions: There has been a substantial shift in the available choice of procedure for BOO surgery around the UK in recent years. However, men can be reassured that overall BOO surgery treatments are safe and effective. Evidence of adherence to guidelines in the preoperative assessment of men with lower urinary tract symptoms undergoing surgery was poorly documented and must be improved., (© 2021 The Authors BJU International © 2021 BJU International.)

Purpose: We investigated the pathological response rates and survival associated with 3 vs 4 cycles of cisplatin-based neoadjuvant chemotherapy (NAC) in patients with cT2-4N0M0 muscle invasive bladder cancer., Materials and Methods: In this cohort study we analyzed clinical data of 828 patients treated with NAC and radical cystectomy between 2000 and 2020. A total of 384 and 444 patients were treated with 3 and 4 cycles of NAC, respectively. Pathological objective response (pOR; ypT0-Ta-Tis-T1 N0), pathological complete response (pCR; ypT0 N0), cancer-specific survival and overall survival were investigated., Results: pOR and pCR were achieved in 378 (45%; 95% CI 42, 49) and 207 (25%; 95% CI 22, 28) patients, respectively. Patients treated with 4 cycles of NAC had higher pOR (49% vs 42%, p=0.03) and pCR (28% vs 21%, p=0.02) rates compared to those treated with 3 cycles. This effect was confirmed on multivariable logistic regression analysis (pOR OR 1.46 p=0.008, pCR OR 1.57, p=0.007). On multivariable Cox regression analysis, 4 cycles of NAC were significantly associated with overall survival (HR 0.68; 95% CI 0.49, 0.94; p=0.02) but not with cancer-specific survival (HR 0.72; 95% CI 0.50, 1.04; p=0.08)., Conclusions: Four cycles of NAC achieved better pathological response and survival compared to 3 cycles. These findings may aid clinicians in counseling patients and serve as a benchmark for prospective trials. Prospective validation of these findings and assessment of cumulative toxicity derived from an increased number of cycles are needed.

We demonstrate the use of an acoustic device to actively encapsulate single red blood cells into individual droplets in a T-junction. We compare the active encapsulation with the passive encapsulation depending on the number of loaded cells as well as the created droplet volumes. This method overcomes the Poisson limitation statistical loading of cells for the passive encapsulation. In our experiments we reach a single cell encapsulation efficiency of 97.9 ± 2.1% at droplet formation rates exceeding 15 Hz.

Purpose: To assess the association of patient age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC)., Materials and Methods: We analyzed data from 1105 patients with MIBC. Patients age was evaluated as continuous variable and stratified in quartiles. Pathologic objective response (pOR; ypT0-Ta-Tis-T1N0) and pathologic complete response (pCR; ypT0N0), as well survival outcomes were assessed. We used data of 395 patients from The Cancer Genome Atlas (TCGA) to investigate the prevalence of TCGA molecular subtypes and DNA damage repair (DDR) gene alterations according to patient age., Results: pOR was achieved in 40% of patients. There was no difference in distribution of pOR or pCR between age quartiles. On univariable logistic regression analysis, patient age was not associated with pOR or pCR when evaluated as continuous variables or stratified in quartiles (all p > 0.3). Median follow-up was 18 months (IQR 6-37). On Cox regression and competing risk regression analyses, age was not associated with survival outcomes (all p > 0.05). In the TCGA cohort, patient with age ≤ 60 years has 7% less DDR gene mutations (p = 0.59). We found higher age distribution in patients with luminal (p < 0.001) and luminal infiltrated (p = 0.002) compared to those with luminal papillary subtype., Conclusions: While younger patients may have less mutational tumor burden, our analysis failed to show an association of age with response to preoperative chemotherapy or survival outcomes. Therefore, the use of preoperative chemotherapy should be considered regardless of patient age., (© 2021. The Author(s).)

Tuberculosis (TB) remains a global healthcare crisis, with an estimated 5.8 million new cases and 1.5 million deaths in 2020. TB is caused by infection with the major human pathogen Mycobacterium tuberculosis , which is difficult to rapidly diagnose and treat. There is an urgent need for new methods of diagnosis, sufficient in vitro models that capably mimic all physiological conditions of the infection, and high-throughput drug screening platforms. Microfluidic-based techniques provide single-cell analysis which reduces experimental time and the cost of reagents, and have been extremely useful for gaining insight into monitoring microorganisms. This review outlines the field of microfluidics and discusses the use of this novel technique so far in M. tuberculosis diagnostics, research methods, and drug discovery platforms. The practices of microfluidics have promising future applications for diagnosing and treating TB.

Background: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) is associated with improved overall and cancer-specific survival. The post-NAC pathological stage has previously been reported to be a major determinant of outcome., Objective: To develop a postoperative nomogram for survival based on pathological and clinical parameters from an international consortium., Design, Setting, and Participants: Between 2000 and 2015, 1866 patients with MIBC were treated at 19 institutions in the USA, Canada, and Europe. Analysis was limited to 640 patients with adequate follow-up who had received three or more cycles of NAC., Outcome Measurements and Statistical Analysis: A nomogram for bladder cancer-specific mortality (BCSM) was developed by multivariable Cox regression analysis. Decision curve analysis was used to assess the model's clinical utility., Results and Limitations: A total of 640 patients were identified. Downstaging to non-MIBC (ypT1, ypTa, and ypTis) occurred in 271 patients (42 %), and 113 (17 %) achieved a complete response (ypT0N0). The 5-yr BCSM was 47.2 % (95 % confidence interval [CI]: 41.2-52.6 %). On multivariable analysis, covariates with a statistically significant association with BCSM were lymph node metastasis (hazard ratio [HR] 1.90 [95% CI: 1.4-2.6]; p < 0.001), positive surgical margins (HR 2.01 [95 % CI: 1.3-2.9]; p < 0.001), and pathological stage (with ypT0/Tis/Ta/T1 as reference: ypT2 [HR 2.77 {95 % CI: 1.7-4.6}; p < 0.001] and ypT3-4 [HR 5.9 {95 % CI: 3.8-9.3}; p < 0.001]). The area under the curve of the model predicting 5-yr BCSM after cross validation with 300 bootstraps was 75.4 % (95 % CI: 68.1-82.6 %). Decision curve analyses showed a modest net benefit for the use of the BCSM nomogram in the current cohort compared with the use of American Joint Committee on Cancer staging alone. Limitations include the retrospective study design and the lack of central pathology., Conclusions: We have developed and internally validated a nomogram predicting BCSM after NAC and radical cystectomy for MIBC. The nomogram will be useful for patient counseling and in the identification of patients at high risk for BCSM suitable for enrollment in clinical trials of adjuvant therapy., Patient Summary: In this report, we looked at the outcomes of patients with muscle-invasive bladder cancer in a large multi-institutional population. We found that we can accurately predict death after radical surgical treatment in patients treated with chemotherapy before surgery. We conclude that the pathological report provides key factors for determining survival probability., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: To evaluate the accuracy and completeness of surgeon-reported radical prostatectomy outcome data across a national health system by comparison with a national dataset gathered independently from clinicians directly involved in patient care., Patients and Methods: Data submitted by surgeons to the British Association of Urological Surgeons (BAUS) radical prostatectomy audit for all men undergoing radical prostatectomy between 2015 and 2016 were assessed by cross linkage to the National Prostate Cancer Audit (NPCA) database. Specific data items collected in both databases were selected for comparison analysis. Data completeness and agreement were assessed by percentages and Cohen's kappa statistic., Results: Data from 4707 men in the BAUS and NPCA databases were matched for comparison. Compared with the NPCA, dataset completeness was higher in the BAUS dataset for type of nerve-sparing procedure (92% vs 42%) and postoperative margin status (89% vs 48%) but lower for readmission (87% vs 100%) and Charlson score (80% vs 100%). For all other variables assessed completeness was comparable. Agreement and data reliability were high for most variables. However, despite good agreement, the inter-cohort reliability was poor for readmission, M stage and Charlson score (κ < 0.30)., Conclusions: For the first time in urology we show that surgeon-reported data from the BAUS radical prostatectomy audit can reliably be used to benchmark peri-operative radical prostatectomy outcomes. For comorbidity data, to assist with risk analysis, and longer-term outcomes, NPCA routinely collected data provide a more comprehensive source., (© 2021 The Authors. BJU International © 2021 BJU International.)

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., (© 2021 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objectives: To assess the efficacy of neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in a retrospective multicentre cohort of patients with cT2N0M0 bladder cancer (BCa) without preoperative hydronephrosis., Patients and Methods: This was a propensity-based analysis of 619 patients. Of these, 316 were treated with NAC followed by RC and 303 with upfront RC. After multiple imputations, inverse probability of treatment weighting (IPTW) was used to account for potential selection bias. Multivariable logistic regression analysis was performed to evaluate the impact of NAC on pathological complete response and downstaging at RC, while IPTW-adjusted Kaplan-Meier curves and Cox regression models were built to evaluate the impact of NAC on overall survival (OS)., Results: After IPTW-adjusted analysis, standardised differences between groups were <15%. A complete response (pT0N0) at final pathology was achieved in 94 (30%) patients receiving NAC and nine (3%) undergoing upfront RC. Downstaging to non-muscle-invasive disease (

Objective: To assess the differential response to neoadjuvant chemotherapy (NAC) in patients with urothelial carcinoma of the bladder (UCB) compared to upper tract urothelial carcioma (UTUC) treated with radical surgery., Patients and Methods: Data from 1299 patients with UCB and 276 with UTUC were obtained from multicentric collaborations. The association of disease location (UCB vs UTUC) with pathological complete response (pCR, defined as a post-treatment pathological stage ypT0N0) and pathological objective response (pOR, defined as ypT0-Ta-Tis-T1N0) after NAC was evaluated using logistic regression analyses. The association with overall (OS) and cancer-specific survival (CSS) was evaluated using Cox regression analyses., Results: A pCR was found in 250 (19.2%) patients with UCB and in 23 (8.3%) with UTUC (P < 0.01). A pOR was found in 523 (40.3%) patients with UCB and in 133 (48.2%) with UTUC (P = 0.02). On multivariable logistic regression analysis, patients with UTUC were less likely to have a pCR (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.27-0.70; P < 0.01) and more likely to have a pOR (OR 1.57, 95% CI 1.89-2.08; P < 0.01). On univariable Cox regression analyses, UTUC was associated with better OS (hazard ratio [HR] 0.80, 95% CI 0.64-0.99, P = 0.04) and CSS (HR 0.63, 95% CI 0.49-0.83; P < 0.01). On multivariable Cox regression analyses, UTUC remained associated with CSS (HR 0.61, 95% CI 0.45-0.82; P < 0.01), but not with OS., Conclusions: Our present findings suggest that the benefit of NAC in UTUC is similar to that found in UCB. These data can be used as a benchmark to contextualise survival outcomes and plan future trial design with NAC in urothelial cancer., (© 2020 The Authors BJU International Published by John Wiley & Sons Ltd on behalf of BJU International.)

Introduction: With the emergence of the COVID-19 pandemic, all elective surgery was temporarily suspended in the UK, allowing for diversion of resource to manage the anticipated surge of critically unwell patients. Continuing to deliver time-critical surgical care is important to avoid excess morbidity and mortality from pathologies unrelated to COVID-19. We describe the implementation and short-term surgical outcomes from a system to deliver time-critical elective surgical care to patients during the COVID-19 pandemic., Materials and Methods: A protocol for the prioritisation and safe delivery of time-critical surgery at a COVID-19 'clean' site was implemented at the Nuffield Health Exeter Hospital, an independent sector hospital in the southwest of England. Outcomes to 30 days postoperatively were recorded, including unplanned admissions after daycase surgery, readmissions and complications, as well as the incidence of perioperative COVID-19 infection in patients and staff., Results: A total of 128 surgical procedures were performed during a 31-day period by a range of specialties including breast, plastics, urology, gynaecology, vascular and cardiology. There was one unplanned admission and and two readmissions. Six complications were identified, and all were Clavien-Dindo grade 1 or 2. All 128 patients had preoperative COVID-19 swabs, one of which was positive and the patient had their surgery delayed. Ten patients were tested for COVID-19 postoperatively, with none testing positive., Conclusion: This study has demonstrated the implementation of a safe system for delivery of time-critical elective surgical care at a COVID-19 clean site. Other healthcare providers may benefit from implementation of similar methodology as hospitals plan to restart elective surgery.

Background: UK Bladder cancer survival remains low. Nonmetastatic muscle-invasive bladder cancer (MIBC) is potentially curable. It is unclear how many patients receive nonradical treatment owing to advanced age, comorbidities, or alternative factors., Objective: To describe treatments and assess survival by disease stage and sex for all newly diagnosed nonmetastatic MIBC in England in 2016, and to observe associations between comorbidities and treatments., Design, Setting, and Participants: All new nonmetastatic MIBC diagnoses in England in 2016 were identified retrospectively using National Cancer Registration and Analysis Service, Radiotherapy Datasets, Systemic Anti-Cancer Therapy, and Hospital Episode Statistics databases., Outcome Measurements and Statistical Analysis: Age, Charlson Comorbidity Index (CCI), and treatments were ascertained, and 1-yr survival was estimated using Pohar-Perme and Kaplan-Meier methods., Results and Limitations: Nonmetastatic MIBC diagnoses were registered for 2519 patients (median age 76 yr). Radical cystectomy was performed in 24%, 37% of whom received neoadjuvant chemotherapy (NAC). Radical radiotherapy was performed in 29%, 48% of whom received NAC. NAC alongside radical treatment was associated with higher 1-yr overall survival (OS)-91% (88-93%) with NAC and 83% (80-85%) without (p = 0.05). Nonradical treatments occurred for 47%, with corresponding lower OS. Females with stage II and III disease had significantly lower net survival (NS). Radically treated patients had lower CCIs., Conclusions: This analysis provides an overview of all nonmetastatic MIBC diagnosed in England in 2016. Just over half of the patients received curative-intent treatment. Of them, only 43% received NAC. One-year OS was disparate, correlating with treatment intensity. Those receiving NAC and radical therapy demonstrated highest OS. Female patients had significantly inferior NS. The data highlight a prescient unmet research need to understand the patient demographic and reasons behind treatment allocation, to address the poor survival observed in those treated nonradically, and the low NAC utilisation. The significantly aged population requires specific future focus., Patient Summary: We looked at all patients in England in 2016 who were diagnosed with bladder cancer invading the bladder muscle. Many patients were elderly, and the most intensive treatments aiming for cure were frequently not used. Survival in women was found to be considerably worse, as was survival for less intensively treated patients., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Background: Prostate surgery can improve lower urinary tract symptoms (LUTS) by relieving bladder outlet obstruction (BOO). However, surgery is less effective without BOO, or if detrusor underactivity is present. Urodynamics (UDS) can identify BOO and measure detrusor activity, but evidence in clinical practice is lacking., Objective: Urodynamics for Prostate Surgery Trial: Randomised Evaluation of Assessment Methods (UPSTREAM) aimed to evaluate whether a care pathway including UDS would reduce surgery without increasing urinary symptoms., Design, Setting, and Participants: UPSTREAM is a pragmatic, noninferiority, randomised controlled trial in men with bothersome LUTS, in whom surgery was an option, in 26 hospitals in England (ISRCTN56164274)., Intervention: Participants were randomised (1:1) to routine care (RC) diagnostic tests, or RC plus UDS., Outcome Measurements and Statistical Analysis: The primary outcome was the International Prostate Symptom Score (IPSS; patient-reported outcome scale from 0 to 35 points) 18 mo after randomisation, with a noninferiority margin of 1 point. Urological surgery rates were a key secondary outcome. The primary outcome was compared between the arms using linear regression, analysed on an intention-to-treat basis., Results and Limitations: Between October 2014 and December 2016, 820 men (median age 68 yr) were randomised (393 and 427 in the RC and UDS arms, respectively). The UDS arm showed noninferiority of the mean IPSSs (UDS 12.6; RC 13.1; adjusted difference at 18 mo -0.33 [95% confidence interval {CI} -1.47, +0.80]). In the UDS arm, 153/408 (38%) received surgery compared with 138/384 (36%) in the RC arm (adjusted odds ratio 1.05; 95% CI 0.77, 1.43). A total of 428 adverse events (UDS 234; RC 194) were recorded, with related events similar in both arms and 11 unrelated deaths., Conclusions: In this population, the UDS randomised group was noninferior to RC for the IPSS but did not reduce surgical rates. This study shows that routine use of UDS in the evaluation of uncomplicated LUTS has a limited role and should be used selectively., Patient Summary: For men with uncomplicated lower urinary tract symptoms, symptom improvements after treatment and the number of operations performed are similar, irrespective of whether or not urodynamic tests are conducted in addition to routine tests. Accordingly, routine use of urodynamics has a limited role in this population group., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: Enhanced Recovery After Surgery (ERAS) is a perioperative approach to managing surgical patients. The impact of ERAS on radical cystectomy (RC) outcomes remains understudied., Objective: To review the literature regarding ERAS protocols and RC outcomes. The primary outcome was hospital length of stay (LOS)., Evidence Acquisition: A systematic review of the articles published from 1970 through 2018 was conducted. Individual patient data (IPD) were requested and a meta-analysis was performed., Evidence Synthesis: A total of 4197 articles were retrieved and 22 (reporting 4048 patients) were selected for the review. LOS followed by 30-d and that followed by 90-d complications were the most common endpoints. ERAS use was associated with reduced morbidity, quicker bowel recovery, and shorter LOS, without affecting mortality. IPD were obtained for 2077 patients from 11 studies. In multivariable models, LOS was associated with ERAS use (regression coefficient: -4.54 [95% confidence interval {CI}: -5.79 to -3.28] d with ERAS p <  0.001) and Charlson Comorbidity Index (+1.64 [1.38-1.90] d for each point increase, p <  0.001), and varied between hospitals (from -1.59 [-3.03 to -0.14] to +4.55 [1.89-7.21] d, p <  0.03). Individual ERAS components associated with shorter LOS included no nasogastric (NG) tube (-8.70 [-11.9 to -5.53] d, p <  0.001) and local anesthesia blocks compared with regional anesthesia (-3.29 [-6.31 to -0.27] d, p =  0.03)., Conclusions: ERAS protocols were associated with reduced LOS and postoperative complication rate. Avoidance of NG tubes and use of local anesthesia blocks were significantly associated with reduced LOS. These findings reflect different components of recovery, which ERAS can optimize and further support documentation of the use of ERAS components when reporting RC outcomes., Patient Summary: Use of enhanced recovery in patients undergoing surgery to remove the bladder is associated with fewer surgical complications and a shorter hospital stay. Avoidance of nasogastric tubes and use of local anesthesia after the operation were associated with a shorter length of stay., (Copyright © 2020 European Association of Urology. All rights reserved.)

Background: Lower urinary tract symptoms (LUTS) in men may indicate bladder outlet obstruction (BOO) or weakness, known as detrusor underactivity (DU). Severe bothersome LUTS are a common indication for surgery. The diagnostic tests may include urodynamics (UDS) to confirm whether BOO or DU is the cause, potentially reducing the number of people receiving (inappropriate) surgery., Objectives: The primary objective was to determine whether a care pathway including UDS is no worse for symptom outcome than one in which it is omitted, at 18 months after randomisation. Rates of surgery was the key secondary outcome., Design: This was a pragmatic, multicentre, two-arm (unblinded) randomised controlled trial, incorporating a health economic analysis and qualitative research., Setting: Urology departments of 26 NHS hospitals in England., Participants: Men (aged ≥ 18 years) seeking further treatment, potentially including surgery, for bothersome LUTS. Exclusion criteria were as follows: unable to pass urine without a catheter, having a relevant neurological disease, currently undergoing treatment for prostate or bladder cancer, previously had prostate surgery, not medically fit for surgery and/or unwilling to be randomised., Interventions: Men were randomised to a care pathway based on non-invasive routine tests (control) or routine care plus invasive UDS (intervention arm)., Main Outcome Measures: The primary outcome was International Prostate Symptom Score (IPSS) at 18 months after randomisation and the key secondary outcome was rates of surgery. Additional secondary outcomes included adverse events (AEs), quality of life, urinary and sexual symptoms, UDS satisfaction, maximum urinary flow rate and cost-effectiveness., Results: A total of 820 men were randomised (UDS, 427; routine care, 393). Sixty-seven men withdrew before 18 months and 11 died (unrelated to trial procedures). UDS was non-inferior to routine care for IPSS 18 months after randomisation, with a confidence interval (CI) within the margin of 1 point (-0.33, 95% CI -1.47 to 0.80). A lower surgery rate in the UDS arm was not found (38% and 36% for UDS and routine care, respectively), with overall rates lower than expected. AEs were similar between the arms at 43-44%. There were more cases of acute urinary retention in the routine care arm. Patient-reported outcomes for LUTS improved in both arms and satisfaction with UDS was high in men who received it. UDS was more expensive than routine care. From a secondary care perspective, UDS cost an additional £216 over an 18-month time horizon. Quality-adjusted life-years (QALYs) were similar, with a QALY difference of 0.006 in favour of UDS over 18 months. It was established that UDS was acceptable to patients, and valued by both patients and clinicians for its perceived additional insight into the cause and probable best treatment of LUTS., Limitations: The trial met its predefined recruitment target, but surgery rates were lower than anticipated., Conclusions: Inclusion of UDS in the diagnostic tests results in a symptom outcome that is non-inferior to a routine care pathway, but does not affect surgical rates for treating BOO. Results do not support the routine use of UDS in men undergoing investigation of LUTS., Future Work: Focus should be placed on indications for selective utilisation of UDS in individual cases and long-term outcomes of diagnosis and therapy., Trial Registration: Current Controlled Trials ISRCTN56164274., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 24, No. 42. See the NIHR Journals Library website for further project information., Competing Interests: Outside this work, Paul Abrams reports grants and personal fees for being a consultant and speaker for Astellas Pharma Inc. (Tokyo, Japan), and personal fees for being a consultant for Ipsen (Paris, France) and a speaker for Pfizer Inc. (New York City, NY, USA) and Sun Pharmaceutical Industries Ltd (Mumbai, India). He also reports personal fees from Pierre Fabre S.A. (Paris, France) and Coloplast Ltd (Peterborough, UK). Christopher Chapple reports being an author for Allergan plc (Dublin, Ireland) and Astellas Pharma; being an investigator for scientific studies/trials with Astellas Pharma and Ipsen; being a patent holder with Symimetics; receiving personal fees as a consultant/advisor for Astellas Pharma, Bayer Schering Pharma GmbH (Berlin, Germany), Ferring Pharmaceuticals (Saint-Prex, Switzerland), Galvani Bioelectronics (GlaxoSmithKline; Stevenage, UK), Pierre Fabre, Symimetics, TARIS Biomedical Inc. (Lexington, MA, USA), and Urovant Sciences (Irvine, CA, USA); and receiving personal fees as a meeting participant/speaker for Astellas Pharma and Pfizer. J Athene Lane was a member of the Clinical Trials Unit funded by the National Institute for Health Research during the conduct of this trial. Marcus J Drake reports being on associated advisory boards and has received grants, personal fees and non-financial support from Allergan, Astellas Pharma and Ferring Pharmaceuticals. He has also received personal fees from Pfizer.

Objective: To assess the effect of patient's sex on response to neoadjuvant chemotherapy (NAC) in patients with clinically nonmetastatic muscle-invasive bladder cancer (MIBC)., Methods: Complete pathologic response, defined as ypT0N0 at radical cystectomy, and downstaging were evaluated using sex-adjusted univariable and multivariable logistic regression modeling. We used interaction terms to account for age of menopause and smoking status. The association of sex with overall survival and cancer-specific survival was evaluated using Cox regression analyses., Results: A total of 1,031 patients were included in the analysis, 227 (22%) of whom were female. Female patients had a higher rate of extravesical disease extension (P = 0.01). After the administration of NAC, ypT stage was equally distributed between sexes (P = 0.39). On multivariable logistic regression analyses, there was no difference between the sexes or age of menopause with regards to ypT0N0 rates or downstaging (all P > 0.5). On Cox regression analyses, sex was associated with neither overall survival (hazard ratio 1.04, 95% confidence interval 0.75-1.45, P = 0.81) nor cancer-specific survival (hazard ratio 1.06, 95% confidence interval 0.71-1.58, P = 0.77)., Conclusion: Our study generates the hypothesis that NAC equalizes the preoperative disparity in pathologic stage between males and females suggesting a possible differential response between sexes. This might be the explanation underlying the comparable survival outcomes between sexes despite females presenting with more advanced tumor stage., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Infections due to Pseudomonas aeruginosa ( P. aeruginosa ) often exhibit broad-spectrum resistance and persistence to common antibiotics. Persistence is especially problematic with immune-compromised subjects who are unable to eliminate the inhibited bacteria. Hence, antibiotics must be used at the appropriate minimum bactericidal concentration (MBC) rather than at minimum inhibitory concentration (MIC) levels. However, MBC determination by conventional methods requires a 24 h culture step in the antibiotic media to confirm inhibition, followed by a 24 h sub-culture step in antibiotic-free media to confirm the lack of bacterial growth. We show that electrochemical detection of pyocyanin (PYO), which is a redox-active bacterial metabolite secreted by P. aeruginosa , can be used to rapidly assess the critical ciprofloxacin level required for bactericidal deactivation of P. aeruginosa within just 2 hours in antibiotic-treated growth media. The detection sensitivity for PYO can be enhanced by using nanoporous gold that is modified with a self-assembled monolayer to lower interference from oxygen reduction, while maintaining a low charge transfer resistance level and preventing electrode fouling within biological sample matrices. In this manner, bactericidal efficacy of ciprofloxacin towards P. aeruginosa at the MBC level and bacterial persistence at the MIC level can be determined rapidly, as validated at later timepoints using bacterial subculture in antibiotic-free media., Competing Interests: Declaration of interests 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.

Objectives: To evaluate the activity of intravesical mitomycin-C (MMC) to ablate recurrent low-risk non-muscle-invasive bladder cancer (NMIBC) and assess whether it may enable patients to avoid surgical intervention for treatment of recurrence., Patients and Methods: CALIBER is a phase II feasibility study. Participants were randomized (2:1) to treatment with four once-weekly MMC 40-mg intravesical instillations (chemoablation arm) or to surgical management. The surgical group was included to assess the feasibility of randomization. The primary endpoint was complete response to intravesical MMC in the chemoablation arm at 3 months, reported with exact 95% confidence intervals (CIs). Secondary endpoints included time to subsequent recurrence, summarized by Kaplan-Meier methods., Results: Between February 2015 and August 2017, 82 patients with visual diagnosis of recurrent low-risk NMIBC were enrolled from 24 UK hospitals (chemoablation, n = 54; surgical management, n =28). The median follow-up was 24 months. Complete response at 3 months was 37.0% (20/54; 95% CI 24.3-51.3) with chemoablation and 80.8% (21/26; 95% CI 60.6-93.4) with surgical management. Amongst patients with complete response at 3 months, a similar proportion was recurrence-free by 12 months in both groups (84%). Amongst those with residual disease at 3 months, the 12-month recurrence-free proportion was lower in the surgical management group (40.0%) than in the chemoablation group (84%). Recruitment stopped early as chemoablation did not meet the prespecified threshold of 45% complete responses at 3 months., Conclusion: Intravesical chemoablation in low-risk NMIBC is feasible and safe, but did not demonstrate sufficient response in the present trial. After chemoablation there may be a reduction in recurrence rate, even in non-responders, that is greater than with surgery alone. Further research is required to investigate the role and optimal schedule of neoadjuvant intravesical chemotherapy prior to surgery for NMIBC., (© 2020 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Microfluidic applications such as active particle sorting or selective enrichment require particle classification techniques that are capable of working in real time. In this paper, we explore the use of neural networks for fast label-free particle characterization during microfluidic impedance cytometry. A recurrent neural network is designed to process data from a novel impedance chip layout for enabling real-time multiparametric analysis of the measured impedance data streams. As demonstrated with both synthetic and experimental datasets, the trained network is able to characterize with good accuracy size, velocity, and cross-sectional position of beads, red blood cells, and yeasts, with a unitary prediction time of 0.4 ms. The proposed approach can be extended to other device designs and cell types for electrical parameter extraction. This combination of microfluidic impedance cytometry and machine learning can serve as a stepping stone to real-time single-cell analysis and sorting. Graphical Abstract.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer lacking specific biomarkers that can be correlated to disease onset, promotion and progression. To assess whether tumor cell electrophysiology may serve as a marker for PDAC tumorigenicity, we use multi-frequency impedance cytometry at high throughput (∼350 cells/s) to measure the electrical phenotype of single PDAC tumor cells from xenografts, which are derived from primary pancreatic tumors versus those from liver metastases of different patients. A novel phase contrast metric based on variations in the high and low frequency impedance phase responses that is related to electrophysiology of the cell interior is found to be systematically altered as a function of tumorigenicity. PDAC cells of higher tumorigenicity exhibited lowered interior conductivity and enhanced permittivity, which is validated by the dielectrophoresis on the respective cell types. Using genetic analysis, we suggest the role of dysregulated Na + transport and removal of Ca 2+ ions from the cytoplasm on key oncogenic KRAS-driven processes that may be responsible for lowering of the interior cell conductivity. We envision that impedance cytometry can serve as a tool to quantify phenotypic heterogeneity for rapidly stratifying tumorigenicity. It can also aid in protocols for dielectrophoretic isolation of cells with a particular phenotype for prognostic studies on patient survival and to tailor therapy selection to specific patients., 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 © 2019 Elsevier B.V. All rights reserved.)

•IDENTIFY study: The largest prospective cohort study of haematuria in secondary care.•Contemporary urinary cancer detection rates and diagnostic strategies.•The effectiveness of diagnostic tests, e.g. ultrasound, in detecting urinary cancer.•Novel patient risk factors associated with bladder and upper tract urinary cancers., Competing Interests: 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., (© 2020 The Authors.)

Introduction: The neutrophil-to-lymphocyte ratio (NLR) is an attractive marker because it is derived from routine bloodwork. NLR has shown promise as a prognostic factor in muscle invasive bladder cancer (MIBC) but its value in patients receiving neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) is not yet established. Since NLR is related to an oncogenic environment and poor antitumor host response, we hypothesized that a high NLR would be associated with a poor response to NAC and would remain a poor prognostic indicator in patients receiving NAC., Methods: A retrospective analysis was performed on patients with nonmetastatic MIBC (cT2-4aN0M0) who received NAC prior to RC between 2000 and 2013 at 1 of 19 centers across Europe and North America. The pre-NAC NLR was used to split patients into a low (NLR ≤ 3) and high (NLR > 3) group. Demographic and clinical parameters were compared between the groups using Student's t test, chi-squared, or Fisher's exact test. Putative risk factors for disease-specific and overall survival were analyzed using Cox regression, while predictors of response to NAC (defined as absence of MIBC in RC specimen) were investigated using logistic regression., Results: Data were available for 340 patients (199 NLR ≤ 3, 141 NLR > 3). Other than age and rate of lymphovascular invasion, demographic and pretreatment characteristics did not differ significantly. More patients in the NLR > 3 group had residual MIBC after NAC than the NLR ≤ 3 group (70.8% vs. 58.3%, P = 0.049). NLR was the only significant predictor of response (odds ratio: 0.36, P = 0.003) in logistic regression. NLR was a significant risk factor for both disease-specific (hazard ratio (HR): 2.4, P = 0.006) and overall survival (HR:1.8, P = 0.02)., Conclusion: NLR > 3 was associated with a decreased response to NAC and shorter disease-specific and overall survival. This suggests that NLR is a simple tool that can aid in MIBC risk stratification in clinical practice., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Surgical trainers consider laparoscopic videos as a useful teaching aid to maximize trainees' learning and skill development given the backdrop of time constraints and productivity demands. Aim of this study is to assess the current use of laparoscopic videos amongst surgical trainees in the United Kingdom., Methods: A steering committee of 15 experienced laparoscopic trainers from 8 countries developed a survey on the use of laparoscopic videos by surgical trainees. The survey items were finalized by discussion through e-mails, teleconferences, and face-to-face meetings and a finalised questionnaire was distributed amongst surgical trainees in the United Kingdom., Results: 92 trainees were invited and 75 returned the questionnaire (81.5%). 86.7% of the trainees routinely watched online surgical videos and the more frequently used websites were Youtube.com and Websurg.com. Trainees require laparoscopic videos to have supplementary educational content such as English commentary (90.7%) and use of snapshots (93.3%) and diagrams (86.7%). Position of the patient and trocars, indication for surgery, preoperative data and postoperative outcomes are required characteristics of laparoscopic videos. 29 trainees (38.7%) do not record the laparoscopic procedures they perform, despite the majority of them recognising the usefulness of routine video-recording for training purposes (78.7%)., Conclusions: Surgical trainees consider videos a useful adjunct in laparoscopic surgery training, with preference for open access sources. Trainees value highly informative videos with supplementary educational content., (Copyright © 2018 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Objectives: To analyse the perioperative and oncological outcomes of all radical prostatectomies (RPs) performed for high-risk prostate cancer in the British Association of Urological Surgeons (BAUS) national registry from 2014 to 2015., Patients and Methods: We identified and analysed outcomes of all RPs performed for high-risk prostate cancer (clinical stage >T2 and/or biopsy Gleason grade >7 and/or preoperative prostate-specific antigen level ≥20 ng/mL) in the national registry for 2014 and 2015. Surgeon reporting of data was mandated during this period. Institution and individual surgeon volume-outcome relationships were assessed., Results: In total, 3671/13 947 (26.3%) patients underwent RP for high-risk prostate cancer over the 2-year period. Robot-assisted RP was the most prevalent approach (60.7%). In all, 39% of men received an extended pelvic lymph node dissection (LND), but over one-third (33.8%) had no LND. Minimally invasive techniques were associated with a significantly shorter length of stay. The reported rates of Clavien-Dindo ≥III complications within the dataset were low (2.0%), regardless of surgical modality or surgeon volume. No statistically significant surgeon volume-outcome relationships were identified when surgeon volume was stratified into tertiles., Conclusion: RP for high-risk prostate cancer in the UK appears safe, regardless of modality used or surgeon volume. No clear evidence that surgeon volume impacts on early perioperative outcomes was seen. Quality assurance of the surgeon-reported BAUS dataset is now required to drive quality improvement in national practice., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)