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Glenn T Werneburg Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH, USACorrespondence: Glenn T Werneburg, Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH, USA, Tel +1 216-444-2200, Email wernebg@ccf.orgAbstract: Catheter-associated urinary tract infection (CAUTI) is the most common healthcare-associated infection and cause of secondary bloodstream infections. Despite many advances in diagnosis, prevention and treatment, CAUTI remains a severe healthcare burden, and antibiotic resistance rates are alarmingly high. In this review, current CAUTI management paradigms and challenges are discussed, followed by future prospects as they relate to the diagnosis, prevention, and treatment. Clinical and translational evidence will be evaluated, as will key basic science studies that underlie preventive and therapeutic approaches. Novel diagnostic strategies and treatment decision aids under development will decrease the time to diagnosis and improve antibiotic accuracy and stewardship. These include several classes of biomarkers often coupled with artificial intelligence algorithms, cell-free DNA, and others. New preventive strategies including catheter coatings and materials, vaccination, and bacterial interference are being developed and investigated. The antibiotic pipeline remains insufficient, and new strategies for the identification of new classes of antibiotics, and rational design of small molecule inhibitor alternatives, are under development for CAUTI treatment.Keywords: catheter-associated urinary tract infection, biofilm, bacterial interference, bacterial competition, chaperone-usher, machine learning

Competing Interests: Declaration of Competing Interest GTW consulting for Atterx Biotherapeutics, Light Line Medical. SPV consultant: Medtronic, Allergan, BlueWind, Axonics. AWM has nothing to disclose.

Objective: To characterize microbial biofilms associated with different device types used in the urological field including ureteral stents, sacral neuromodulation (SNM) devices, penile prostheses, and artificial urinary sphincters (AUS)., Materials and Methods: Data from 4 studies, each reporting biofilm composition of a particular device type, were pooled and included for inter-device analysis. Studies recruited adults scheduled for ureteral stent, SNM, IPP, or AUS removal/revision. Device (n = 115) biofilms and controls were analyzed with multi-omics approaches, and compositions were compared across device types and clinical factors., Results: Microbiota present on each device type was distinct from that of perineal, rectal, or urine flora (P <.01). Biofilm microbial counts (P <.001) and diversity (P = .024) differed by device type. Ureteral stents had greater microbial counts than other device types (P <.001). Staphylococcus, Pseudomonas, Lactobacillus, Ureaplasma were commonly detected across devices. Device biofilms harbored a greater proportion of Proteobacteria phylum, and the rectal, perineal, and urine flora harbored a greater proportion of Firmicutes. Unique microbe-metabolite interaction networks were identified in presence and absence of infection. Antibiotic-resistance genes including sul2 (sulfonamide resistance) and rpoB (rifampin resistance) were detected in biofilms across device types. Biofilm reconstitution in vitro differed by device type from which strains were isolated., Conclusion: Ureteral stents, sacral neuromodulation devices, penile prostheses, and artificial urinary sphincters harbored unique microbial and metabolite profiles that differed from those of skin, urine, and rectal flora. The findings of this study set the groundwork for investigation of novel strategies to reduce device-associated infection risk within and outside urology., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/ personal relationships, which may be considered as potential competing interests: GTW consulting for Atterx Biotherapeutics, Light Line Medical; HBG consultant: Abbvie, Medtronic, BlueWind; SPV consultant: Medtronic, Allergan, BlueWind, Axonics., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: Urinary tract infections are one of the most common reasons for antibiotic prescription. The widespread use of antibiotic treatments contributes to the global health problem of antimicrobial resistance development. To slow down the progression of antimicrobial resistance, it is essential that we explore nonantibiotic preventive treatments for this common condition. We aim to report discussions regarding nonantibiotic preventive strategies for recurrent urinary tract infections in both catheterized and non-catheterized patients that took place at the International Consultation on Incontinence-Research Society meeting in Bristol in 2024., Methods: We undertook a think-tank session during this multidisciplinary meeting specifically designated for discussion regarding both established and emerging nonantibiotic treatments for UTI prevention in both catheterized and non-catheterized patients. This led to the generation of pertinent research questions, which hope to shape future UTI research., Results: We describe the discussions that took place and document the important research questions that were proposed during the International Consultation on Incontinence-Research Society meeting in Bristol in 2024., Conclusions: There is a range of established UTI preventative strategies for UTI prevention in both catheterized and non-catheterized patients. Emerging UTI prevention treatments have varying levels of evidence to support their use, and in many areas, further research is needed to establish their place in clinical pathways., (© 2024 Wiley Periodicals LLC.)

Objective: To develop, externally validate, and test a series of computer algorithms to accurately predict antibiotic susceptibility test (AST) results at the time of clinical diagnosis, up to 3 days before standard urine culture results become available, with the goal of improving antibiotic stewardship and patient outcomes., Patients and Methods: Machine learning algorithms were developed and trained to predict susceptibility or resistance using over 4.7 million discrete AST classifications from urine cultures in a cohort of adult patients from outpatient and inpatient settings from 2012 to 2022. The algorithms were validated on a cohort from a geographically-distant hospital system, ~1931 km (~1200 miles) from the training cohort facilities, from the same time period. Finally, algorithms were clinically validated in a contemporary cohort and compared to the empiric therapy prescribed by clinicians. Appropriateness of the antibiotics selected by clinicians and the algorithm during the clinical validation was compared., Results: Algorithms were accurate during clinical validation (area under the receiver operating characteristic curve [AUC] 0.71-0.94) for all 11 tested antibiotics. The algorithms' accuracy improved as the organism was identified (AUC 0.79-0.97). In external validation in a geographically-distant cohort, the algorithms remained accurate even without additional training on this group (AUC 0.69-0.87). When the algorithms were trained on the antibiogram from the geographically-distant hospital, the accuracy improved (AUC 0.70-0.93). When algorithms' performances were tested against clinicians in a contemporary cohort for the empiric prescription of oral antibiotics, the drug agent suggested by the algorithms more frequently resulted in adequate empiric coverage., Conclusions: Machine learning algorithms trained on a large dataset are accurate in prediction of urine culture susceptibility vs resistance up to 3 days prior to urine AST availability. Clinical implementation of such an algorithm could improve both clinical care and antimicrobial stewardship., (© 2024 BJU International.)

Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/ personal relationships, which may be considered as potential competing interests: GTW consultant for Atterx Biotherapeutics and Light Line Medical; medical advisory board member for Renascent Diagnostics, whose products are unrelated to this study; HBG: consultant for Abbvie and Medtronic; SPV consultant for Medtronic, Allergan, BlueWind, Axonics.

Objective: To predict treatment response for overactive bladder (OAB) for a specific patient remains elusive. We sought to develop accurate models using machine learning for prediction of objective and patient-reported treatment response to intravesical botulinum toxin (OBTX-A) injection. We sought to validate the models in a challenging setting using an external dataset of a markedly different patient cohort and dosing regimen. We hypothesized the model would outperform human experts and top available algorithms., Methods: Algorithms using "operator splitting" designed for accuracy and efficiency even in small training datasets with variable completeness, were trained to predict objective response and patient-reported symptomatic improvement using the ROSETTA trial cohort and validated using the ABC trial cohort of patients who underwent OBTX-A. Areas under the curve (AUC) of algorithms were compared to the top publicly-available machine-learning classifier XGBoost, logistic regression with cross validation, and human expert predictions in the external validation set., Results: In the validation set, the operator splitting neural network had AUC of 0.66 and outperformed XGBoost with DART (top available machine-learning classifier, AUC: 0.58), logistic regression (AUC 0.55), and human experts (AUC 0.47-0.53) for prediction of clinical responder status. It was similarly accurate in prediction of patient subjective improvement in symptoms following OBTX-A (AUC: 0.64), again outperforming other algorithms and human experts (AUC 0.41-0.62)., Conclusion: The neural network outperformed human experts and other machine-learning approaches in prediction of objective and patient-reported OBTX-A outcomes for OAB in a challenging independent validation cohort. Clinical implementation could improve counseling and treatment selection., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GTW consultant for Atterx Biotherapeutics and Light Line Medical, whose products are unrelated to this study. EAW has no disclosures. HBG: consultant for Abbvie and Medtronic. ES has no disclosures. LHR has no disclosures. SPV consultant for Medtronic, Allergan, BlueWind, Axonics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Standard laboratory cultures and biomarkers for urologic conditions have limitations that have led to great interest in microbiome testing in urology. Microbiome testing may play a role in clinical urology in the future in areas such as diagnosis of infections, biomarkers for diagnosis and prognosis of functional and oncological conditions, and targeted microbial modulation to augment existing treatment modalities and reduce disease risk., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The urine culture is imperfect, and a series of alternative approaches are in development to assist in diagnosis, treatment, and prevention of urinary tract infection (UTI). Culture-independent approaches typically do not distinguish between viable and nonviable bacteria, and are generally not included in current clinical guidance. Next-generation sequencing may play an important future role in precise targeting of antibiotic treatment of asymptomatic bacteriuria prior to endourologic surgery or in pregnancy. Future studies are needed to determine whether microbiota modulation could prevent UTI. Possible modulation mechanisms may include fecal microbiota transplant, application of topical vaginal estrogen or probiotics, and bacteriophage therapy., Competing Interests: Disclosures GW consultant: Atterx Biotherapeutics, Light Line Medical. MH. Hsieh: none. Clinical trial registration: This manuscript is not a clinical trial and thus does not warrant registration as such. Ethics of approval and patient consent: n/a., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To determine accuracy of negative urinalysis (UA) for predicting negative urine culture and the absence of urinary tract infection (UTI), and optimal urine culture growth cutoff for UTI diagnosis in men with and without urinary catheters., Subjects and Methods: UAs with urine cultures within 1 week from adult men were identified and evaluated. Predictive values for the absence of UTI (absence of ≥1 of the following criteria: documentation of UTI diagnosis, antibiotic prescription, uropathogen presence on culture) were calculated., Results: In total, 22 883 UAs were included. Negative UA had a high predictive value for negative urine culture (0.95, 95% confidence interval [CI]: 0.94-0.95) and absence of UTI (0.99, CI: 0.99-0.995) in the overall cohort. Negative UA also had a high predictive value for negative urine culture (0.93, CI: 0.90-0.95) and absence of UTI (0.99, CI: 0.98-0.999) in those with indwelling urinary catheters. The traditional threshold of culture growth of 100 000 colony-forming units (CFU)/mL did not capture 22% of UTIs., Conclusion: UA exhibits high predictive value for negative urine culture and absence of UTI in men, supporting a protocol wherein culture is only performed in the context of abnormal UA. The traditional 100 000 CFU/mL cut-off may have not captured a subset of UTI in the male population, and warrants further investigation., (© 2024 The Author(s). Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Competing Interests: Declaration of Competing Interest GTW—consultant for Atterx Biotherapeutics and Light Line Medical; AWM—no conflict.

Aims: The integration of artificial intelligence (AI) into functional urology management must be assessed for its clinical utility, but hopefully will change, perhaps to revolutionize the way LUTD and other conditions are assessed, the aim being to offer patients more rapid and effective management which enhances patient outcomes. The aim of this proposal, discussed at the ICI-RS annual meeting, is to evaluate the available evidence on AI and the way it might change the approach to urodynamic (UDS) diagnoses, including overactive bladder syndrome (OAB), and perhaps other LUTDs such as bladder outflow obstruction., Methods: A compendium of discussion based on the current evidence related to AI and its potential applications in UDS and OAB., Results: AI-powered diagnostic tools are being developed to analyze complex datasets from urodynamic studies, imaging, and other diagnostic tests. AI systems can leverage large volumes of clinical data to recommend personalized treatment plans based on individual patient profiles to optimize surgical procedures, enhance diagnostic precision, tailor the therapy, reduce the risk of complications, and improve outcomes. In the future, AI will be able to provide tailored counseling regarding the outcomes and potential side effects of drugs and procedures to a given patient., Conclusion: AI's role in functional urology has been poorly investigated, and its implementation across several areas may improve clinical care and the pathophysiological understanding of functional urologic conditions., (© 2024 Wiley Periodicals LLC.)

Urinary tract infection (UTI) is among the most common human bacterial infections. In the context of increasing antibiotic resistance, there are many research efforts to improve the pathophysiological understanding, diagnosis, and treatment of UTI. Despite the high clinical relevance of UTI, there is high variability in definitions in the literature, making interpretation and comparison of research studies difficult, and even impossible in some cases. A recent Delphi consensus study generated a new reference standard definition for UTI that incorporates symptoms, pyuria, and urine culture results. This definition allows for designation of systemic involvement, and no longer categorizes UTIs as complicated or uncomplicated. The definition aligns with guidance from regulatory bodies for approval of UTI drugs. Implementation of a reference standard definition in the design and reporting of future investigations will allow better research design and interpretability within and outside the urology field. The new reference standard resolves some issues and offers a suitable way to unify methodology, and hence increase the potential strength of research in this area. There are some limitations and challenges for implementation, such as difficulties in establishing sensitivity and specificity values for the various settings in which the definition will be used. The inclusion of "probable" and "possible" UTI categories could be a problem in studies that require dichotomous outcomes. Nonetheless, the reference standard should be recommended until new developments become available, notably a more specific UTI biomarker than pyuria. Approaches to standardized diagnosis of catheter-associated UTIs remain unresolved. PATIENT SUMMARY: A new research definition for urinary tract infection (UTI) has been developed. Use of a single standardized definition in research will help in better design of research studies and comparison of results. Although the new definition will help in reducing the variability in UTI research reports, it has some limitations and there may be challenges to overcome before it is widely used., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Objective: Lower urinary tract symptoms (LUTS) and overactive bladder (OAB) intimately affect the psychological wellbeing and mental health of men. However, to date, the association of aggression with LUTS and OAB has not been investigated. To address this knowledge gap, we evaluated the association of aggression with LUTS and OAB in a large representative cohort of men at the population level., Methods: We used computer-assisted web interviews that included reliable questionnaires for assessment of LUTS, OAB, and aggression. A population-representative group of men was based on the most recent census. For data analysis, we developed univariate and multivariate regression models., Key Findings and Limitations: We analyzed data for a cohort of 3001 men that was representative for age and place of residence. Aggression was more prevalent among respondents with LUTS and OAB in comparison to men without these conditions ( p  < 0.001). The scores for aggression were directly proportional to the scores for LUTS and OAB (Spearman's rank correlation coefficients of 0.261 for LUTS and 0.284 for OAB). Univariate linear regression models revealed an association between aggression and LUTS or OAB in all age groups. Finally, multivariable linear regression models confirmed that correlations of aggression with LUTS and OAB were independent of age, sociodemographic parameters, comorbidities, and lifestyle habits (regression coefficients of 0.013 for LUTS and 0.024 for OAB)., Conclusions and Clinical Implications: Our study is the first to show that aggression among men is consistently associated with LUTS and OAB. Our results open a new research area on the effect of LUTS and OAB or their causes on psychological wellbeing and mental health, and may even support screening for hostile behavior in the clinical setting for individuals who report LUTS and OAB., Patient Summary: We performed the first study to investigate whether aggression is linked to lower urinary tract symptoms (LUTS) and overactive bladder (OAB). Results from our survey in a representative group of men in Poland show that aggression is linked to LUTS and OAB. More research is needed to confirm these results., (© 2024 The Author(s).)

Introduction/purpose: Sacral neuromodulation (SNM) is effective therapy for overactive bladder refractory to oral therapies, and non-obstructive urinary retention. A subset of SNM devices is associated with infection requiring surgical removal. We sought to compare microbial compositions of explanted devices in the presence and absence of infection, by testing phase, and other clinical factors, and to investigate antibiotic resistance genes present in the biofilms. We analyzed resistance genes to antibiotics used in commercially-available anti-infective device coating/pouch formulations. We further sought to assess biofilm reconstitution by material type and microbial strain in vitro using a continuous-flow stir tank bioreactor, which mimics human tissue with an indwelling device. We hypothesized that SNM device biofilms would differ in composition by infection status, and genes encoding resistance to rifampin and minocycline would be frequently detected., Materials/methods: Patients scheduled to undergo removal or revision of SNM devices were consented per IRB-approved protocol (IRB 20-415). Devices were swabbed intraoperatively upon exposure, with controls and precautions to reduce contamination of the surrounding field. Samples and controls were analyzed with next-generation sequencing and RT-PCR, metabolomics, and culture-based approaches. Associations between microbial diversity or microbial abundance, and clinical variables were then analyzed using t-tests and ANOVA. Reconstituted biofilm deposition in vitro using the bioreactor was compared by microbial strain and material type using plate-based assays and scanning electron microscopy., Results: Thirty seven devices were analyzed, all of which harbored detectable microbiota. Proteobacteria, Firmicutes and Actinobacteriota were the most common phyla present overall. Beta-diversity differed in the presence versus absence of infection (p = 0.014). Total abundance, based on normalized microbial counts, differed by testing phase (p < 0.001), indication for placement (p = 0.02), diabetes mellitus (p < 0.001), cardiac disease (p = 0.008) and history of UTI (p = 0.008). Significant microbe-metabolite interaction networks were identified overall and in the absence of infection. 24% of biofilms harbored the tetA tetracycline/minocycline resistance gene and 53% harbored the rpoB rifampin resistance gene. Biofilm was reconstituted across tested strains and material types. Ceramic and titanium did not differ in biofilm deposition for any tested strain., Conclusions: All analyzed SNM devices harbored microbiota. Device biofilm composition differed in the presence and absence of infection and by testing phase. Antibiotic resistance genes including to rifampin and tetracycline/minocycline, which are used in commercially-available anti-infective pouches, were frequently detected. Isolated organisms from SNM devices demonstrated the ability to reconstitute biofilm formation in vitro. Biofilm deposition was similar between ceramic and titanium, materials used in commercially-available SNM device casings. The findings and techniques used in this study together provide the basis for the investigation of the next generation of device materials and coatings, which may employ novel alternatives to traditional antibiotics. Such alternatives might include bacterial competition, quorum-sensing modulation, or antiseptic application, which could reduce infection risk without significantly selecting for antibiotic resistance., (© 2024 The Author(s). Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Purpose of Review: Transgender and gender-diverse individuals (TGD) are at risk for sexually transmitted infections. Gender affirmation surgery is a cornerstone of care for many TGD individuals. For genital gender affirmation, the surgical creation of a vagina may be performed through a number of techniques. Those who have undergone vaginoplasty have unique anatomical and biopsychosocial considerations, which we discuss., Recent Findings: While sexually-transmitted infections including HPV, HSV, HIV, gonorrhea, and chlamydia, have been described in TGD individuals after vaginoplasty, the reports are very rare, and the provider should maintain an index of suspicion and maintain a broad differential for symptoms including neovaginal discharge. We discuss the association of the neovaginal microbiota composition with bacterial vaginosis, and how its modulation could potentially reduce bacterial vaginosis and sexually transmitted infection risk., Summary: We examine the literature regarding sexually-transmitted infections following vaginoplasty, and the neovaginal microbiome and its similarities and differences relative to the natal vaginal microbiome., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

In order to establish a causal relationship between urinary microbiota and a urological disease or condition, a series of rigorous scientific criteria must be met. Demonstration of an association between microbiota and a condition does not necessarily imply causality, importance, or clinical relevance., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Bladder compliance is the relationship between detrusor pressure and bladder storage volume. We discuss the definition of compliance, how it may be accurately measured, and its clinical relevance. Specifically, we discuss the association between low compliance and upper urinary tract deterioration. We discuss medical and surgical therapies that have been demonstrated to improve compliance and reduce upper tract risk. Finally, we propose a model, which not only considers compliance but also differential pressure between the bladder and ureters, and how this may also be an accurate predictor of upper tract deterioration. We call for further investigation to test this model., Competing Interests: Disclosure G.T. Werneburg declares that he has no conflict of interest. J.T. Stoffel: Scientific Advisor Flume Catheter, Spine X; Site investigator Coloplast clinical trial., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To characterize the surgical management, perioperative, and cancer-specific outcomes, and the influence of aggressive histologic variants (AHV) on operative management among patients with renal cell carcinoma (RCC) and inferior vena cava (IVC) thrombus. RCC with rhabdoid and/or sarcomatoid differentiation, which we defined as AHV, portends a worse prognosis. AHV can be associated with a desmoplastic reaction which may complicate resection., Methods: We reviewed patients undergoing radical nephrectomy and IVC thrombectomy between 1990 and 2020. Comparative statistics were employed as appropriate. Survival analysis was performed according to the Kaplan-Meier method, and intergroup analysis performed with log-rank statistics. Multivariable cox proportional hazards regression was used to assess the effect of AHV, age, thrombus level, vena cavectomy, metastases, and medical comorbidities on recurrence and overall survival (OS)., Results: Ninety-four of 403 (23.3%) patients had AHV, including 43 (46%) rhabdoid, 39 (41%) sarcomatoid, and 12 (13%) with both. AHV were more likely to present with advanced disease; however, increased perioperative complications or decreased OS were not observed. Median (IQR) survival was 16.7 (4.8-47) months without AHV and 12.6 (4-29) months with AHV (P = .157). Sarcomatoid differentiation was independently associated with worse OS (HR = 2.016, CI 1.38-2.95, P <.001), whereas rhabdoid alone or with sarcomatoid demonstrated similar OS (P = 0.063)., Conclusion: RCC and IVC thrombus with AHV are more likely to present with metastatic disease, and sarcomatoid differentiation is associated with a worse OS. Resection of tumors with and without AHV have similar perioperative complications, suggesting that surgery can be safely accomplished in patients with RCC and IVC thrombus with AHV., Competing Interests: Declaration of Competing Interest All authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Culture-based studies have shown that penile prostheses harbor biofilms in the presence and absence of infection, but these findings have not been adequately validated using contemporary microbiome analytic techniques., Aim: The study sought to characterize microbial biofilms of indwelling penile prosthesis devices according to patient factors, device components, manufacturer, and infection status., Methods: Upon penile prostheses surgical explantation, device biofilms were extracted, sonicated, and characterized using shotgun metagenomics and culture-based approaches. Device components were also analyzed using scanning electron microscopy., Outcomes: Outcomes included the presence or absence of biofilms, alpha and beta diversity, specific microbes identified and the presence of biofilm, and antibiotic resistance genes on each prosthesis component., Results: The average age of participants from whom devices were explanted was 61 ± 11 years, and 9 (45%) of 20 had a diagnosis of diabetes mellitus. Seventeen devices were noninfected, and 3 were associated with clinical infection. Mean device indwelling time prior to explant was 5.1 ± 5.1 years. All analyzed components from 20 devices had detectable microbial biofilms, both in the presence and absence of infection. Scanning electron microscopy corroborated the presence of biofilms across device components. Significant differences between viruses, prokaryotes, and metabolic pathways were identified between individual patients, device manufacturers, and infection status. Mobiluncus curtisii was enriched in manufacturer A device biofilms relative to manufacturer B device biofilms. Bordetella bronchialis, Methylomicrobium alcaliphilum, Pseudoxanthomonas suwonensis, and Porphyrobacter sp. were enriched in manufacturer B devices relative to manufacturer A devices. The most abundant bacterial phyla were the Proteobacteria, Actinobacteria, and Firmicutes. Glycogenesis, the process of glycogen synthesis, was among the predominant metabolic pathways detected across device components. Beta diversity of bacteria, viruses, protozoa, and pathways did not differ among device components., Clinical Implications: All components of all penile prostheses removed from infected and noninfected patients have biofilms. The significance of biofilms on noninfected devices remains unknown and merits further investigation., Strengths and Limitations: Strengths include the multipronged approach to characterize biofilms and being the first study to include all components of penile prostheses in tandem. Limitations include the relatively few number of infected devices in the series, a relatively small subset of devices included in shotgun metagenomics analysis, and the lack of anaerobic and other expanded conditions for culture., Conclusion: Penile prosthesis biofilms are apparent in the presence and absence of infection, and the composition of biofilms was driven primarily by device manufacturer, individual variability, and infection, while being less impacted by device component., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.)

To understand differences between asymptomatic colonized and infected states of indwelling medical devices, we sought to determine penile prosthesis biofilm composition, microbe-metabolite interaction networks, and association with clinical factors. Patients scheduled for penile prosthesis removal/revision were included. Samples from swabbed devices and controls underwent next-generation sequencing, metabolomics, and culture-based assessments. Biofilm formation from device isolates was reconstituted in a continuous-flow stir tank bioreactor. 93% of 27 analyzed devices harbored demonstrable biofilm. Seven genera including Faecalibaculum and Jeotgalicoccus were more abundant in infected than uninfected device biofilms (p < 0.001). Smokers and those with diabetes mellitus or cardiac disease had lower total normalized microbial counts than those without the conditions (p < 0.001). We identified microbe-metabolite interaction networks enriched in devices explanted for infection and pain. Biofilm formation was recapitulated on medical device materials including silicone, PTFE, polyurethane, and titanium in vitro to facilitate further mechanistic studies. Nearly all penile prosthesis devices harbor biofilms. Staphylococcus and Escherichia, the most common causative organisms of prosthesis infection, had similar abundance irrespective of infection status. A series of other uncommon genera and metabolites were differentially abundant, suggesting a complex microbe-metabolite pattern-rather than a single organism-is responsible for the transition from asymptomatic to infected or painful states., (© 2023. The Author(s).)

Objective: To assess predictive value of urinalysis for negative urine culture and absence of urinary tract infection, re-evaluate the microbial growth threshold for positive urine culture result, and describe antimicrobial resistance features. Urine culture is associated with 27% of U.S. hospitalizations, and unnecessary antibiotic prescription is a main antibiotic resistance contributor., Methods: Urinalyses with urine culture from women ages 18-49 from 2013 to 2020 were studied. Clinically diagnosed urinary tract infection (CUTI) was defined as (1) uropathogen growth, (2) documented diagnosis of urinary tract infection, and (3) antibiotic prescription. Sensitivity, specificity, and diagnostic predictive values were used to assess urinalysis performance in predicting isolation of a uropathogen by culture and in detection of CUTI., Results: Total 12,252 urinalyses were included. Forty-one percent of urinalyses were associated with positive urine culture and 1287 (10.5%) with CUTI. Negative urinalysis exhibited high predictive accuracy for negative urine culture (specificity 90.3%, PPV 87.3%) and absence of CUTI (specificity 92.2%, PPV 97.4%). Twenty-four percent of patients not meeting the CUTI definition were still prescribed antibiotics. Twenty-two percent of cultures associated with CUTI exhibited growth less than 100,000 CFU/mL. Escherichia coli was implemented as causing 70% of CUTIs, and 4.2% of these produced an extended spectrum beta-lactamase., Conclusion: Negative urinalysis exhibits high predictive accuracy for absence of CUTI. A reporting threshold of 10,000 CFU/mL is more clinically appropriate than a 100,000 CFU/mL cutpoint. Reflex culture based on urinalysis results could complement clinical judgement and improve laboratory and antibiotic stewardship in premenopausal women., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: We sought to determine microbe-metabolite composition and interactions within indwelling ureteral stent biofilms, determine their association with patient factors including infection, and reconstitute biofilm formation on relevant surface materials in vitro., Materials and Methods: Upon ureteral stent removal from patients, proximal and distal ends were swabbed. Samples were analyzed by 16S next-generation sequencing and metabolomics. A continuous-flow stir-tank bioreactor was used to reconstitute and quantify in vitro biofilm formation from stent-isolated bacteria on stent-related materials including silicone, polytetrafluoroethylene, polyurethane, polycarbonate, and titanium. Diversity, relative abundance, and association with clinical factors were analyzed with ANOVA and Bonferroni t -tests or PERMANOVA. Biofilm deposition by microbial strain and device material type were analyzed using plate counts and scanning electron microscopy following bioreactor incubation., Results: All 73 samples from 37 ureteral stents harbored microbiota. Specific genera were more abundant in samples from stents wherein there was antibiotic exposure during indwelling time ( Escherichia/Shigella, Pseudomonas, Staphylococcus , Ureaplasma ) and in those associated with infection ( Escherichia/Shigella , Ureaplasma ). The enriched interaction subnetwork in stent-associated infection included Ureaplasma and metabolite 9-methyl-7-bromoeudistomin. Strains identified as clinically relevant and central to interaction networks all reconstituted biofilm in vitro, with differential formation by strain ( Enterococcus faecalis most) and material type (titanium least)., Conclusions: Ureteral stent biofilms exhibit patterns unique to stent-associated infection and antibiotic exposure during indwelling time. Microbes isolated from stents reconstituted biofilm formation in vitro. This work provides a platform to test novel materials, evaluate new coatings for anti-biofilm properties, and explore commensal strain use for bacterial interference against pathogens.

Introduction and Hypothesis: The objective was to accurately predict patient-centered subjective outcomes following the overactive bladder (OAB) treatments OnabotulinumtoxinA (OBTX-A) injection and sacral neuromodulation (SNM) using a neural network-based machine-learning approach. In the context of treatments designed to improve quality of life, a patient's perception of improvement should be the gold standard outcome measure., Methods: Cutting-edge neural network-based algorithms using reproducing kernel techniques were trained to predict patient-reported improvements in urinary leakage and bladder function as assessed by Patient Global Impression of Improvement score using the ROSETTA trial datasets. Blinded expert urologists provided with the same variables also predicted outcomes. Receiver operating characteristic curves and areas under the curve were generated for algorithm and human expert predictions in an out-of-sample holdout dataset., Results: Algorithms demonstrated excellent accuracy in predicting patient subjective improvement in urinary leakage (OBTX-A: AUC 0.75; SNM: 0.80). Similarly, algorithms accurately predicted patient subjective improvement in bladder function (OBTX-A: AUC 0.86; SNM: 0.96). The top-performing algorithms outcompeted human experts across outcome measures., Conclusions: Novel neural network-based machine-learning algorithms accurately predicted OBTX-A and SNM patient subjective outcomes, and generally outcompeted expert humans. Subtle aspects of the physician-patient interaction remain uncomputable, and thus the machine-learning approach may serve as an aid, rather than as an alternative, to human interaction and clinical judgment., (© 2022. The International Urogynecological Association.)

Background: Patients undergoing simultaneous liver-kidney transplantation (SLK) have impaired native kidney function. The relative contribution of allograft versus native function after SLK is unknown. We sought to characterize the return of native kidney function following SLK., Methods: Following SLK, patients underwent technetium-99 m-mercaptoacetyltriglycine renal scintigraphy following serum creatinine nadir. Kidney contributions to estimated glomerular filtration rate (eGFR) were determined. Patients with native kidney function at serum creatinine nadir contributing eGFR ≥30 versus <30 mL/min/1.73 m 2 were compared, and multiple linear regression analysis for native eGFR improvement was performed., Results: Thirty-one patients were included in this analysis. Average native kidney contribution to overall kidney function following SLK was 51.1% corresponding to native kidney eGFR of 44.5 mL/min/1.73 m 2 and native kidney function eGFR improvement of 30.3 mL/min/1.73 m 2 ( P < 0.001). Twenty-six of 31 patients had native kidney contribution of eGFR ≥30 mL/min/1.73 m 2 . Hepatorenal syndrome as the sole primary etiology of kidney dysfunction was 100% specific for native kidney eGFR >30 mL/min/1.73 m 2 and predicted native eGFR improvement ( P = 0.03)., Conclusions: Substantial improvement in native kidney function follows SLK, and hepatorenal syndrome as the sole primary etiology of kidney dysfunction is predictive of improvement. Whether such patients are suitable for liver transplant followed by surveillance with option for subsequent kidney transplants requires investigation., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Individuals with neuromuscular disorders and neurogenic lower urinary tract dysfunction are commonly nonweight-bearing with lower lean muscle mass than the general population. We sought to compare estimated glomerular filtration rate equations that include creatinine, cystatin C, or both, in nonweight-bearing individuals and matched ambulatory controls., Materials and Methods: Records were reviewed for individuals with serum creatinine (Cr) and cystatin C (Cys) and diagnosis consistent with nonweight-bearing status, and matched ambulatory controls. The 2021 CKD-EPI (Chronic Kidney Disease-Epidemiology Collaboration) race agnostic equations were used to calculate estimated glomerular filtration rate. Renal function was compared by equation in the overall cohorts and in a patient subset with imaging and/or urinalysis evidence of renal dysfunction., Results: Nonweight-bearing (n = 102) and control populations (n = 204) had similar demographics. In the nonweight-bearing population, estimated glomerular filtration rate differed when calculated using CKD-EPI Cr , CKD-EPI Cr+Cys, and CKD-EPI Cys (107, 93, 80 mL/min/1.73 m 2 , respectively, P < .001). The differences in estimated glomerular filtration rate were greater in the nonweight-bearing relative to the control group regardless of CKD-EPI equation pairs compared ( P < .001). In the patient subset with imaging and/or proteinuria evidence of renal dysfunction, the nonweight-bearing population again had different estimated glomerular filtration rate when calculated using CKD-EPI Cr , CKD-EPI Cr+Cys , and CKD-EPI Cys ( P < . 001). Fifty-eight percent of nonweight-bearing individuals with evidence of renal dysfunction on imaging or urinalysis were reclassified into a lower estimated glomerular filtration rate category when using estimated glomerular filtration rate Cys relative to estimated glomerular filtration rate Cr ., Conclusions: Estimated glomerular filtration rate equations containing serum creatinine, cystatin C, or both, validated in mostly ambulatory populations, are not equivalently accurate in estimating kidney function in nonweight-bearing individuals. Comparison of these equations against gold standard glomerular filtration rate measurement is needed to determine which most closely approximates true glomerular filtration rate.

Neurogenic lower urinary tract dysfunction (NLUTD), the abnormal function of the lower urinary tract in the context of neurological pathology, has been the subject of multiple efforts worldwide for the development of clinical practice guidelines. These guidelines are based on the same body of evidence, and are therefore subject to the same gaps. For example, sexual and bowel dysfunction in the context of NLUTD, optimal renal function assessment in those who are non-ambulatory or with low muscle mass, optimal upper tract surveillance timing, and modification of diagnostic and treatment modalities for low-resource nations and communities are inadequately addressed. In addition, many aspects of the conclusions and final recommendations of the guidelines are similar. This duplicative work represents a large expenditure of time and effort, which we believe could be focused instead on evidence gaps. Here, we call for a global unified approach to create a single, resource-independent, comprehensive guidance on NLUTD, neurogenic sexual, and neurogenic bowel dysfunction. Targeted research addressing the evidence gaps should be called for and pursued. This will allow for focus to shift to filling the gaps in the evidence for future guidelines.

The artificial urinary sphincter (AUS) is an effective treatment option for incontinence due to intrinsic sphincteric deficiency in the context of neurogenic lower urinary tract dysfunction, or stress urinary incontinence following radical prostatectomy. A subset of AUS devices develops infection and requires explant. We sought to characterize biofilm composition of the AUS device to inform prevention and treatment strategies. Indwelling AUS devices were swabbed for biofilm at surgical removal or revision. Samples and controls were subjected to next-generation sequencing and metabolomics. Biofilm formation of microbial strains isolated from AUS devices was reconstituted in a bioreactor mimicking subcutaneous tissue with a medical device present. Mean patient age was 73 (SD 10.2). All eighteen artificial urinary sphincter devices harbored microbial biofilms. Central genera in the overall microbe−metabolite interaction network were Staphylococcus (2620 metabolites), Escherichia/Shigella (2101), and Methylobacterium-Methylorubrum (674). An rpoB mutation associated with rifampin resistance was detected in 8 of 15 (53%) biofilms. Staphylococcus warneri formed greater biofilm on polyurethane than on any other material type (p < 0.01). The results of this investigation, wherein we comprehensively characterized the composition of AUS device biofilms, provide the framework for future identification and rational development of inhibitors and preventive strategies against device-associated infection.

The urine culture, the cornerstone for laboratory diagnosis of urinary tract infection (UTI), is associated with a high frequency of false-positive and false-negative results, and its diagnostic threshold is debated. Urine culture takes days to result, and antibiotics are often initiated while awaiting final culture readings. Further, asymptomatic bacteriuria-the presence of bacteria in urine in the absence of UTI symptoms-generally does not warrant treatment. The authors review current expert guidance on the use of urine culture, including approaches to ordering, processing, and reporting of urine cultures, with the goal of reducing unnecessary antibiotic use and misdiagnosis of UTI., (Copyright © 2022 The Cleveland Clinic Foundation. All Rights Reserved.)

Objective: To identify differences in neuroinflammatory gene expression in individuals with chronic orchialgia (CO) compared to asymptomatic controls., Methods: Vas deferens, spermatic cord fascia, blood, and urine were collected from 9 men with CO at time of microscopic spermatic cord denervation and 7 asymptomatic controls at time of vasectomy. RNA was isolated and analyzed with the NanoString Human Neuroinflammation panel. Data were normalized, gene expression fold changes and enriched pathways relative to asymptomatic controls were determined. Gene expression was considered significantly different if there was a >2-fold change and P-value <.05 relative to controls., Results: Mean patient age was 51 years and median symptom duration 12 months. There were 26 genes with significantly differential expression in vas deferens. cFos, a marker of nociceptive pain, had the greatest difference (30.2-fold change, P <.000001). Enriched pathways in vas deferens included nerve function, matrix remodeling, and innate immune responses. In fascia, cFos also had the greatest differential expression (38-fold, P = .000002), followed by S100A12 (11-fold, inducer of innate immune response). Enriched pathways in fascia included nerve function and inflammation. In blood, there were no differentially expressed genes, and in urine there were 95 differentially expressed genes., Conclusion: Men with CO have a diverse set of neuroinflammatory genes with differential expression in tissue and urine relative to healthy controls. These findings confirm pathologic changes in tissue targeted by denervation surgery, and suggest molecular changes in neuropathic pain that could lead to biomarker identification and novel treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To understand the mechanistic basis for reduced infectious complications in transperineal (TP) prostate biopsy, we sought to determine whether TP prostate biopsy is associated with a lower degree of pathogen introduction into the prostate relative to transrectal (TR) biopsy., Materials and Methods: In men scheduled for prostate biopsy for standard clinical indications, rectal and perineal skin swabs, and 2 extra biopsy cores, were obtained. Specimens underwent DNA extraction followed by next-generation sequencing and standard laboratory culture. Microbial quantity and composition were determined and compared between prostate core biopsy tissue from individuals who underwent TP vs TR biopsy., Results: Twenty-three men were accrued to the study. Biopsy core tissue from the TP group had less microbial diversity (15.0 vs 25.8 phylogenetic clades/sample, P = .0004) and had a lower quantity of known pathogens (36.3 vs 104.2 normalized counts of pathogens/sample, P = .018) relative to the TR group. TP group tissue core flora was more attributable to the perineal than rectal source (P = .047). Viable Escherichia coli was isolated from 45% of the TR group cores, but none in the TP group (P = .014)., Conclusion: Biopsy tissue from individuals who undergo TP biopsy harbors a lower human pathogenic bacterial load than those who undergo TR biopsy, with a minimal risk of viable E. coli. Our results elucidate a possible mechanism for reduced infectious risk associated with TP biopsy relative to TR biopsy and a rational basis for widespread implementation of TP biopsy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To evaluate prostate cancer screening occurrence in patients with spinal cord injury at our institution compared to a matched, unaffected population., Materials and Methods: We conducted a retrospective review of patients with the criteria: male, age 50-70, and diagnosis of cerebral palsy, spina bifida, or quadriplegia. A control cohort was matched by age, race, insurance, and co-morbidities. Prostate specific antigen (PSA) screening, PSA value, prostate MRI, prostate biopsy, and biopsy outcome were compared. Multivariate logistic regression analysis was performed to determine the association between patient variables and PSA screening., Results: The study cohort and control cohort included 2180 patients each. Patients with spinal cord injury had significantly lower rates of PSA screening (15% vs 24%, P <.00001), MRI (0.1% vs 0.6%, P = .02), and biopsy (0.6% vs 1.3%, P = .01) compared to control. Spinal cord injury was associated with a lower likelihood of PSA screening (OR = 0.56, CI = 0.48-0.65, P <.00001). There were no significant differences in PSA value and biopsy outcomes., Conclusion: Patients with spinal cord injury had a lower likelihood of PSA screening compared to a matched control population. Since PSA screening is a shared-decision making process, providers should consider the increasing life expectancy of patients with spinal cord injury and risks of under-testing for prostate cancer., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The increasing wealth of clinical data may become unmanageable for a physician to assimilate into optimal decision-making without assistance. Utilizing a novel machine learning (ML) approach, we sought to develop algorithms to predict patient outcomes following the overactive bladder treatments OnabotulinumtoxinA (OBTX-A) injection and sacral neuromodulation (SNM)., Materials and Methods: ROSETTA datasets for overactive bladder patients randomized to OBTX-A or SNM were obtained. Novel ML algorithms, using reproducing kernel techniques were developed and tasked to predict outcomes including treatment response and decrease in urge urinary incontinence episodes in both the OBTX-A and SNM cohorts, in validation and test sets. Blinded expert urologists also predicted outcomes. Receiver operating characteristic curves were generated and AUCs calculated for comparison to lines of ignorance and the expert urologists' predictions., Results: Trained algorithms demonstrated outstanding accuracy in predicting treatment response (OBTX-A: AUC 0.95; SNM: 0.88). Algorithms accurately predicted mean decrease in urge urinary incontinence episodes (MSE < 0.15) in OBTX-A and SNM. Algorithms were superior to human experts in response prediction for OBTX-A, and noninferior to human experts in response prediction for SNM., Conclusions: Novel ML algorithms were accurate, superior to expert urologists in predicting OBTX-A outcomes, and noninferior to expert urologists in predicting SNM outcomes. Some aspects of the physician-patient interaction are subtle and uncomputable, and thus ML may complement, but not supplant, a physician's judgment., (© 2022 Wiley Periodicals LLC.)

Background: We sought to study differential neuroinflammatory gene expression in men with interstitial cystitis (IC) with Hunner lesions compared with asymptomatic controls using NanoString, which uses barcoded probes to measure hundreds of genes. IC is a heterogenous condition lacking reliable biomarkers, and a subset of patients exhibits Hunner lesions, implicating the bladder as an inflammatory pain generator., Methods: Blood, urine, and bladder biopsies were collected from 6 men with IC and Hunner lesions. 7 asymptomatic controls had blood and urine collected and 2 benign bladder biopsies were obtained from our tissue bank. RNA was isolated and analyzed with NanoString Human Neuroinflammation panel. Gene expression was considered significant if there was a >1.5-fold change and adjusted P value <0.05 compared with controls., Results: Mean patient age was 61.5 years with 8 years median symptom duration. In bladder tissue, while many cytokine and chemokine genes had higher expression as expected (e.g., TNF , CXCL10 ), other significant genes included TRPA1 (1098-fold increased, expressed in pain sensing neurons) and TNFRSF17 (735-fold, B-cell related). In urine, there was 114-fold increase in S1PR4 , which mediates pain via TRP-dependent pathways. A patient on cyclosporine had lower inflammatory gene expression levels relative to other IC patients, but no difference in TRPA1 ., Conclusions: Men with IC and Hunner lesions have a diverse set of neuroinflammatory genes with differential expression compared to controls. We identified genes linked to neuropathic pain through the TRP pathway and this expression was not reduced by cyclosporine. These findings open a new direction for biomarker and therapeutic discovery., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tau-21-657). DAS serves as an unpaid editorial board member of Translational Andrology and Urology from August 2020 to July 2022. DAS reports investment interest in Triurol. The other authors have no conflicts of interest to declare., (2021 Translational Andrology and Urology. All rights reserved.)

Introduction: Enhanced recovery after surgery protocols and increased attention to value-based care have led to the reconsideration of routine postoperative admission in female pelvic medicine and reconstructive surgery (FPMRS) cases. We aimed to assess trends in same-day discharge (SDD) and associated readmissions and emergency room visits in a single-surgeon 10-year experience., Methods: The electronic medical record was queried for 30-day outcomes (readmission and emergency department visits with associated indications) for all cases performed between June 2010 and August 2020 by a single FPMRS surgeon. Non-FPMRS specialty cases were excluded. Patient characteristics and 30-day outcomes were compared based on SDD status for the overall cohort as well as the subset of cases traditionally involving an overnight stay (i.e., robotic transabdominal, apical prolapse repair)., Results: 1793 surgeries were identified and analyzed, including 357 apical prolapse repairs, 370 slings, 392 neuromodulation and 114 complex mesh excisions. The majority (79.1%) had SDD. For admitted patients, mean length of stay was 1.5 (1.3) days. Among cases traditionally involving overnight stay, rates of SDD were significantly higher in 2020 than 2010 (84% vs. 32%, p < 0.001), and increased over time. Overall rates of 30-day readmission and ED visits were low (1.9% and 2.6%, respectively) and did not differ based on SDD status (p = 0.76). Readmissions occurred at mean 11.6 (7.0) days, most commonly for urinary tract infection (13/34)., Conclusions: SDD is not associated with increased 30-day readmission or ED visits across a wide breadth of FPMRS cases. SDD is safe and feasible in the majority of FPMRS cases., (© 2021 Wiley Periodicals LLC.)

Uropathogenic Escherichia coli assemble surface structures termed pili or fimbriae to initiate infection of the urinary tract. P pili facilitate bacterial colonization of the kidney and pyelonephritis. P pili are assembled through the conserved chaperone-usher pathway. Much of the structural and functional understanding of the chaperone-usher pathway has been gained through investigations of type 1 pili, which promote binding to the bladder and cystitis. In contrast, the structural basis for P pilus biogenesis at the usher has remained elusive. This is in part due to the flexible and variable-length P pilus tip fiber, creating structural heterogeneity, and difficulties isolating stable P pilus assembly intermediates. Here, we circumvent these hindrances and determine cryo-electron microscopy structures of the activated PapC usher in the process of secreting two- and three-subunit P pilus assembly intermediates, revealing processive steps in P pilus biogenesis and capturing new conformational dynamics of the usher assembly machine., (© 2021. The Author(s).)

We present a question regarding the management of a patient with recurrent urinary tract infections (UTIs) following multiple procedures for benign prostatic hyperplasia (BPH)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To compare standard cultures and next-generation sequencing (NGS) in men with chronic prostatitis/chronic pelvic pain syndrome (CPPS). CPPS shares clinical features with urinary tract infections, but bacteria are seldom found. NGS is more sensitive than standard cultures., Materials and Methods: Men diagnosed with CPPS (National Institute of Health Category III) underwent traditional cultures and NGS of their urine and expressed prostatic secretions (EPS). Characteristics between groups were compared statistically., Results: Thirty-one men with CPPS were included (mean age 44.5). All standard urine cultures were negative, and 3 EPS cultures were positive. Seventy-eight unique microbes were detected with NGS, including uropathogens in 10 of the men. There were no bacteria identified by NGS in EPS that were not also found in the urine. Men with positive NGS did not differ from those without in age, symptom severity or phenotype. Men with typical urinary tract infection symptoms (eg, dysuria, chills) were more likely to have uropathogens detected on NGS relative to men without such symptoms. Nine patients were prescribed antibiotics based on their NGS findings, but only 1 exhibited symptom improvement (11%)., Conclusion: NGS commonly identified bacteria in CPPS patients, but these did not localize to the prostate. NGS positivity did not correlate with symptom severity and antibiotic therapy was seldom effective. NGS detected uropathogens more frequently in those with clinical symptoms suggestive of urinary tract infection. Clinical trials are needed to examine the utility of NGS-guided antibiotics in this subpopulation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: We sought to determine the composition and initiation site of bacterial biofilm on indwelling urinary catheters and to track biofilm progression with time., Materials and Methods: Indwelling urinary catheters were collected from 2 tertiary care centers following removal from patients. Indwelling time was noted and catheters were de-identified. Catheters were sectioned, stained for biofilms and analyzed by spectrophotometry and visualization. Biofilm colonization patterns were analyzed using descriptive statistical analysis and bacterial composition was determined using next generation sequencing., Results: We collected and analyzed a total of 33 catheters from 26 males and 7 females with indwelling time ranging from 15 minutes to 43 days. Biofilm colonization was consistently high on the region of the balloon for all indwelling times. After week 1 the distal third of the catheter had higher biofilm colonization than the proximal third (week 2 p=0.034). At all indwelling times the intraluminal surface of the catheter had greater biofilm colonization than the outer surface. Next generation sequencing detected potential uropathogenic bacteria in all 10 analyzed samples., Conclusions: The catheter balloon, its distal aspect and its lumen were the predominant locations of biofilm comprising uropathogenic bacteria. Strategies to prevent or treat biofilm should be targeted to these areas.

Pathogenic bacteria such as Escherichia coli assemble surface structures termed pili, or fimbriae, to mediate binding to host-cell receptors 1 . Type 1 pili are assembled via the conserved chaperone-usher pathway 2-5 . The outer-membrane usher FimD recruits pilus subunits bound by the chaperone FimC via the periplasmic N-terminal domain of the usher. Subunit translocation through the β-barrel channel of the usher occurs at the two C-terminal domains (which we label CTD1 and CTD2) of this protein. How the chaperone-subunit complex bound to the N-terminal domain is handed over to the C-terminal domains, as well as the timing of subunit polymerization into the growing pilus, have previously been unclear. Here we use cryo-electron microscopy to capture a pilus assembly intermediate (FimD-FimC-FimF-FimG-FimH) in a conformation in which FimD is in the process of handing over the chaperone-bound end of the growing pilus to the C-terminal domains. In this structure, FimF has already polymerized with FimG, and the N-terminal domain of FimD swings over to bind CTD2; the N-terminal domain maintains contact with FimC-FimF, while at the same time permitting access to the C-terminal domains. FimD has an intrinsically disordered N-terminal tail that precedes the N-terminal domain. This N-terminal tail folds into a helical motif upon recruiting the FimC-subunit complex, but reorganizes into a loop to bind CTD2 during handover. Because both the N-terminal and C-terminal domains of FimD are bound to the end of the growing pilus, the structure further suggests a mechanism for stabilizing the assembly intermediate to prevent the pilus fibre diffusing away during the incorporation of thousands of subunits.

Background: Technological advancements have led to the success of minimally invasive treatment modalities for prostate cancer such as CyberKnife and Cryotherapy. Here, we investigate patient-reported urinary function, bowel habits, and sexual function in patients following CyberKnife (CK) or Cryotherapy treatment, and compare them with active holistic surveillance (AHS) patients., Methods: An IRB-approved institutional database was retrospectively reviewed for patients who underwent CK, Cryotherapy, or AHS. Quality of life (QoL) survey responses were collected every three months and the mean function scores were analyzed in yearly intervals over the 4 years post-treatment., Results: 279 patients (767 survey sets) were included in the study. There was no difference among groups in urinary function scores. The CyberKnife group had significantly lower bowel habit scores in the early years following treatment (year 2 mean difference: -5.4, P < 0.01) but returned to AHS level scores by year 4. Cryotherapy patients exhibited initially lower, but not statistically significant, bowel function scores, which then improved and approached those of AHS. Both CyberKnife (year 1 mean difference: -26.7, P < 0.001) and Cryotherapy groups (-35.4, P < 0.001) had early lower sexual function scores relative to AHS, but then gradually improved and were not significantly different from AHS by the third year post-treatment. A history of hormonal therapy was associated with a lower sexual function scores relative to those patients who did not receive hormones in both CyberKnife (-18.45, P < 0.01) and Cryotherapy patients (-14.6, P < 0.05)., Conclusions: After initial lower bowel habits and sexual function scores, CyberKnife or Cryotherapy-treated patients had no significant difference in QoL relative to AHS patients. These results highlight the benefit of CyberKnife and Cryotherapy in the management of organ-confined prostate cancer.

Objective: To investigate the effects of focal (hemiablation) or total cryotherapy and minimum tumor temperature on patient-reported quality of life (QoL) in patients with prostate cancer., Methods: An Institutional Review Board-approved database was reviewed for patients who underwent cryotherapy or active surveillance (AS). QoL questionnaire responses were collected and scores were analyzed for differences between focal and total cryotherapy and between very cold (<-76°C) and moderate-cold (≥-76°C) minimum tumor temperatures., Results: A total of 197 patients responded to a total of 547 questionnaires. Focal and total cryotherapy patients had initially lower sexual function scores relative to AS (year 1 mean difference focal: -31.7, P <.001; total: -48.1, P <.001). Focal cryotherapy was associated with a more rapid improvement in sexual function. Both focal and total cryotherapy sexual function scores were not statistically significantly different from the AS cohort by postprocedural year 4. Very cold and moderate-cold temperatures led to initially lower sexual function scores relative to AS (year 1 very cold: -38.1, P <.001; moderate-cold: -30.7, P <.001). Moderate-cold temperature scores improved more rapidly than those of very cold temperature. Neither very cold nor moderate-cold temperatures had a statistically significant difference in sexual function scores relative to AS by postprocedural year 4. Urinary function and bowel habits were not significantly different between focal and total cryotherapy and between very cold and moderate-cold temperature groups., Conclusion: Focal cryotherapy and moderate-cold (≥-76°C) temperature were associated with favorable sexual function relative to total cryotherapy and very cold temperature, respectively. No significant differences in urinary function or bowel habits were observed between groups., (Copyright © 2017 Elsevier Inc. All rights reserved.)