BACKGROUND Urodynamic studies are commonly performed in women before surgery for stress urinary incontinence, but there is no good evidence that they improve outcomes. METHODS We performed a multicenter, randomized, noninferiority trial involving women with uncomplicated, demonstrable stress urinary incontinence to compare outcomes after preoperative office evaluation and urodynamic tests or evaluation only. The primary outcome was treatment success at 12 months, defined as a reduction in the score on the Urogenital Distress Inventory of 70% or more and a response of “much better” or “very much better” on the Patient Global Impression of Improvement. The predetermined noninferiority margin was 11 percentage points. RESULTS A total of 630 women were randomly assigned to undergo office evaluation with urodynamic tests or evaluation only (315 per group); the proportion in whom treatment was successful was 76.9% in the urodynamic-testing group versus 77.2% in the evaluation-only group (difference, −0.3 percentage points; 95% confidence interval, −7.5 to 6.9), which was consistent with noninferiority. There were no significant between-group differences in secondary measures of incontinence severity, quality of life, patient satisfaction, rates of positive provocative stress tests, voiding dysfunction, or adverse events. Women who underwent urodynamic tests were significantly less likely to receive a diagnosis of overactive bladder and more likely to receive a diagnosis of voiding-phase dysfunction, but these changes did not lead to significant between-group differences in treatment selection or outcomes. CONCLUSIONS For women with uncomplicated, demonstrable stress urinary incontinence, preoperative office evaluation alone was not inferior to evaluation with urodynamic testing for outcomes at 1 year. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT00803959.)
Recent advances in the analysis of microbial communities colonizing the human body have identified a resident microbial community in the human urinary tract (UT). Compared to many other microbial niches, the human UT harbors a relatively low biomass. Studies have identified many genera and species that may constitute a core urinary microbiome. However, the contribution of the UT microbiome to urinary tract infection (UTI) and recurrent UTI (rUTI) pathobiology is not yet clearly understood. Evidence suggests that commensal species within the UT and urogenital tract (UGT) microbiomes, such as Lactobacillus crispatus, may act to protect against colonization with uropathogens. However, the mechanisms and fundamental biology of the urinary microbiome-host relationship are not understood. The ability to measure and characterize the urinary microbiome has been enabled through the development of next-generation sequencing and bioinformatic platforms that allow for the unbiased detection of resident microbial DNA. Translating technological advances into clinical insight will require further study of the microbial and genomic ecology of the urinary microbiome in both health and disease. Future diagnostic, prognostic, and therapeutic options for the management of UTI may soon incorporate efforts to measure, restore, and/or preserve the native, healthy ecology of the urinary microbiomes.
Background Female urinary microbiota (FUM) are associated with urgency urinary incontinence (UUI) and response to UUI medication. FUM of women with stress urinary incontinence (SUI) has not been described. Objective Study the cross-sectional relationships between FUM features and demographic and clinical characteristics of women undergoing SUI surgery. Design, Setting, and Participants Pre-operative urine specimens were collected from women without urinary tract infection and were available from 197 women (174 voided, 23 catheterized) enrolled in a multi-center prospective randomized trial, the Value of Urodynamic Evaluation (ValUE) study. Demographic and clinical variables were obtained including SUI and UUI symptoms, menopausal status, and hormone use. Outcome Measurements and Statistical Analysis The bacterial composition of the urine was qualitatively assessed by sequencing the bacterial 16S rRNA gene. Phylogenetic relatedness and microbial alpha diversity were compared to demographics and symptoms using generalized estimating equation models. Results The majority of 197 urine samples (86%) had detectable bacterial DNA. Bacterial diversity was significantly associated with higher BMI (p=0.02), increased Medical, Epidemiologic, and Social Aspects of Aging (MESA) urge index score (p=0.04), and hormonal status (p<0.001). No associations were detected with SUI symptoms. Increased diversity was also associated with a concomitant lower frequency of Lactobacillus in hormone-negative women. Conclusions Women undergoing SUI surgery have detectable urinary microbiota. This cross-sectional analysis revealed that increased diversity of the microbiota was associated with UUI symptoms, hormonal status and BMI. In contrast, the FUM was not associated with stress urinary incontinence symptoms.
Invasive pathogens interface with the host and its resident microbiota through interkingdom signaling. The bacterial receptor QseC, which is a membrane-bound histidine sensor kinase, responds to the host stress hormones epinephrine and norepinephrine and the bacterial signal AI-3, integrating interkingdom signaling at the biochemical level. Importantly, the QseC signaling cascade is exploited by many bacterial pathogens to promote virulence. Here, we translated this basic science information into development of a potent small molecule inhibitor of QseC, LED209. Extensive structure activity relationship (SAR) studies revealed that LED209 is a potent prodrug that is highly selective for QseC. Its warhead allosterically modifies lysines in QseC, impairing its function and preventing the activation of the virulence program of several Gram-negative pathogens both in vitro and during murine infection. LED209 does not interfere with pathogen growth, possibly leading to a milder evolutionary pressure toward drug resistance. LED209 has desirable pharmacokinetics and does not present toxicity in vitro and in rodents. This is a unique antivirulence approach, with a proven broad-spectrum activity against multiple Gram-negative pathogens that cause mammalian infections.
Although the genitourinary consequences of MS are rarely life threatening, they can cause significant morbidity and patient frustration. With the rapid advances in the medical management of MS the urologist should be actively involved in multispecialty treatment of these patients.
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