Background Much of our knowledge about the impact of urinary incontinence (UI) on children is derived from surveys. While these studies provide an overview of the UI experience, personal interviews may offer additional nuances and a more detailed perspective of what the experience of UI is for children. Objective To conduct interviews and use qualitative analysis to explore the experiences of children with UI, with a particular focus on (1) the impact of UI on participants' lives, (2) which coping strategies children with UI use, and (3) the emotional effects of UI. Study design Semi-structured interviews of children with non-neurogenic and non-anatomic UI recruited from a pediatric urology clinic were audio recorded and verbatim transcribed. Eligibility included: age 8-17 years, history of UI, English fluency, and being able to participate in a 30 min interview. Conventional content analysis was performed to identify themes directly from the transcripts. Coders independently and iteratively coded transcripts (intercoder reliability >0.85) until inductive thematic saturation was achieved. Results There were substantial practical and emotional impacts on the 30 (14 males, 16 females) children (median age 11.5 years) with UI. Participants relayed significant interference with social activities like sports and sleepovers, which often lead to avoidant behavior of these activities. By contrast, most stated that UI did not impair school performance. The most strongly and consistently expressed emotions were embarrassment and anxiety. Nevertheless, children described a wide variety of adaptations, including behavioral and cognitive, to manage their incontinence and its effects on their lives (Summary Table). Discussion This is the first qualitative study that describes the experiences and perspectives of children with UI. Surveys of this population suggest a lower health-related quality of life, particularly in emotional well-being, self-esteem and relationships. This work augments this body of literature and shows how UI interferes with their daily life and is a major source of embarrassment and anxiety. Despite this, children with UI display strong resilience and adapt to their condition. The study was limited in that the sample was biased to those presenting to a urology clinic and was not designed to compare differences in UI experience between ages, genders, or treatment types. Conclusion This study, the first qualitative exploration of the emotional responses and coping behaviors of children with UI, shows significant social impact and negative emotional responses but marked resiliency. These findings should be considered when developing a comprehensive treatment strategy for children with UI. [GRAPHICS] .

Purpose. The workup and surveillance strategies for infant hydronephrosis (HN) vary, although this could be due to grade-dependent differences in imaging intensity. We aimed to describe the frequency of imaging studies for HN within the first year of life, stratified by initial HN grade, within a large regional healthcare system. Study Design and Data Source. Retrospective cohort using Intermountain Healthcare Data Warehouse. Inclusion criteria: (1) birth between 1/1/2005 and 12/31/2013, (2) CPT code for HN, and (3) ultrasound (U/S) confirmed HN within four months of birth. Data Collection. Grade of HN on initial postnatal U/S; number of HN-associated radiologic studies (renal U/Ss, voiding cystourethrograms (VCUGs), and diuretic renal scans); demographic and medical variables. Primary Outcome. Sum of radiologic studies within the first year of life or prior to pyeloplasty. Statistical Analysis. Multivariate poisson regression to analyze association between the primary outcome and the initial HN grade. Results. Of 1,380 subjects (993 males and 387 females), 990 (72%), 230 (17%), and 160 (12%) had mild, moderate, and severe HN, respectively. Compared with those with mild HN, patients with moderate (RR: 1.57; 95% CI: 1.42–1.73) and severe (RR: 2.09; 95% CI: 1.88–2.32) HN had a significantly higher rate of imaging use over 12 months (or prior to surgery) after controlling for potential confounders. Conclusions. In a large regional healthcare system, imaging use for HN is proportional to its initial grade. This suggests that within our system, clinicians treating this condition are using a risk-stratified approach to imaging.

Asymptomatic bacteriuria (ASB) is a common finding in many populations, including healthy women and persons with underlying urologic abnormalities. The 2005 guideline from the Infectious Diseases Society of America recommended that ASB should be screened for and treated only in pregnant women or in an individual prior to undergoing invasive urologic procedures. Treatment was not recommended for healthy women; older women or men; or persons with diabetes, indwelling catheters, or spinal cord injury. The guideline did not address children and some adult populations, including patients with neutropenia, solid organ transplants, and nonurologic surgery. In the years since the publication of the guideline, further information relevant to ASB has become available. In addition, antimicrobial treatment of ASB has been recognized as an important contributor to inappropriate antimicrobial use, which promotes emergence of antimicrobial resistance. The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.

17.4%) and benign prostate hyperplasia in 233/304 (76.7%) patients.Mean catheter time was 2.2d and mean hospitalization stay 2.4d.14/304 (4.6%) Patients had a post-operative UTI.Logistic regression could not show a significant difference in favor of AMP (4.3% vs. 4.7% ; p 0.9) in developing UTI in general or complicated UTI (2.2% vs. 3.4% ; p 0.52).A statistical, non-significant decrease in bacteriuria at time of hospital discharge (5.2% vs. 12.5% ; p 0.57) or at the follow-up consultation (6.3% vs. 15% ; p 0.4) was observed.CONCLUSIONS: Our preliminary results shows no significant difference in post-operative UTI in favor of AMP in TURP, meaning we can safely continue our study.A slight but statistical not-significant decrease in post-operative bacteriuria at time of hospital discharge and at the follow-up consultation after 4 weeks is observed.Further data collecting and analysis is needed to confirm our preliminary findings.

OBJECTIVE To evaluate how previous antimicrobial resistance, prior prescription data, and patient place of residence (ZIP code) can guide empirical therapy for uncomplicated urinary tract infections (UTI). Guidelines recommend empirical antimicrobial selection for women with symptoms of uncomplicated UTIs, most commonly trimethoprim-sulfamethoxazole (SXT), nitrofurantoin (NIT), or ciprofloxacin (CIP). Previous antimicrobial resistance and prior prescription data are potential predictors of resistance in subsequent urine cultures for UTIs. Also, there is evidence of geographic clustering of antimicrobial resistance for UTIs. METHODS Retrospective data from women (age >= 18) with an assigned diagnosis of UTI, submitting urine cultures as outpatients (2011-2018), were gathered. Univariate analyses and multivariable regression models were used to determine odds ratios for predicting resistance to SXT, NIT, and CIP on the 2011-2017 data. Antimicrobial choice algorithms were created using 2011-2017 results and tested on 2018 data. RESULTS In the training cohort, 9455 women had diagnoses of uncomplicated UTIs and positive urine cultures. Prevalence of resistance for SXT, NIT, and CIP was 19.4%, 12.1%, and 10.3%, respectively. A urine culture with previous resistance, prior antimicrobial prescription within 2 years and ZIP code were the strongest predictors of a subsequent resistant culture. An algorithm based on these data had a success rate of 92.2%, compared to provider's choice (87.5%, P <.001) or best theoretical outcomes with guidelines (90.0%, P = .048). CONCLUSION Previous resistance, prior prescriptions, and patient ZIP code are predictors of subsequent resistance in patients with uncomplicated UTIs. Algorithms using these data can outperform real-world outcomes and guidelines. (C) 2019 Elsevier Inc.

Purpose: Guidelines recommend treating women who have symptoms of an uncomplicated urinary tract infection with antimicrobials without performing a urine culture. However, 10% to 50% of women with urinary tract infection symptoms are found to have a negative culture. Urinalysis data are useful to predict a negative culture. We evaluated how a previous negative culture predicts the likelihood of a subsequent negative culture. Materials and Methods: We gathered retrospective data on women 18 years old or older with symptoms of an uncomplicated urinary tract infection who submitted urine cultures as outpatients from 2011 to 2017. Univariate analysis and multivariable regression models were used to determine the likelihood ratios and risk ratios of predicting a negative culture. Results: Of the 20,759 patients 9,271 (44.7%) had a negative culture, defined as less than 10(3) CFU/ml, and 6,958 (33.5%) had at least 1 prior culture, including 4,510 (64.8%) with at least 1 prior negative culture and 2,634 (58.4%) with a subsequent negative culture. Variables associated with an increased likelihood of another negative culture were a prior negative culture (LR 1.43, 95% CI 1.387-1.475), prior negative culture and negative urinalysis (LR 1.839, 95% CI 1.768-1.913), and vaginal irritation and/or discharge (LR 1.335, 95% CI 1.249-1.427, each p<0.001). Urinalysis had 83% specificity and 78% positive predictive value. These values were significantly enhanced if the patient had a prior negative culture without a prior positive culture (95% and 87%, respectively). Conclusions: In women with recurrent urinary tract infection symptoms a previous negative culture and negative urinalysis are highly predictive of another negative culture. Women with recurrent urinary tract infection symptoms, and negative urinalysis and urine cultures may benefit from further evaluation.

Purpose We reviewed and collated information concerning the available tools for the measurement of symptoms and outcomes in pediatric continence. Materials and methods MEDLINE, EMBASE, and CINHAL databases were searched for relevant articles published prior to December 2016 and independently screened by two researchers. Expert opinion was also widely sought through consultation with the ICCS Board membership and their professional networks and the multidisciplinary authorship group. The most relevant materials were then selected for analysis and inclusion and resulted in a document available on the ICCS website for all members to review. Insights and feedback were considered with consensus and agreement reached to modify the document. Results and conclusions A variety of useful tools for the assessment and measurement of bladder and bowel dysfunction and quality of life and behavioral comorbidities are presented together with their indications and potential pitfalls. ICCS cannot recommend one over another as the most useful for each clinician will vary depending on the clinical setting, available time, and patient population. We provide a framework for choosing those that are most appropriate based on our findings.

maintained at day7 after LPS injection.Comprehensive cytokine assay (ELISA) showed that more than 2 folds of down-regulation of both inflammatory promoting cytokines (IL-1 alpha, IL-6) and chemokines (CCL3, CXCL1) were observed in epididymitis model of IDO KO mice compared with WT mice.On the other hand, more than 1.5 folds of upregulation of inflammatory inhibiting cytokines (IL-4, IL-10) were observed in epididymitis model of IDO KO mice.The peak expression of IL-1 alpha, IL-6, CCL3 and CXCL1 were at day1 and that of IL-4 was at day3.The expression of IL-10 increased in time dependent manner.Same results were introduced from separate quantitative analysis and immunohistochemical staining.After treatment of IDO inhibition and LPS, IL-1 alpha, IL-6, CCL3 and CXCL1 were significantly downregulated anytime in time series compared with WT mice using ELISA method (p<0.05).IL-4 and IL-10 were significantly up-regulated anytime in time series compared with WT mice (p<0.05).In the group of IDO inhibition, epididymal ductal structure was maintained at day7 after LPS injection and little invasion of inflammatory cells were observed anytime in time series.CONCLUSIONS: IDO should be involved in epididymal immunological reaction via cytokines.To inhibit IDO would contribute to protection of epididymis tissue when inflammation occurs in epididymis.Therefore, IDO might be a novel target for the therapy of the epididymitis in addition to antibodiotics.

IntroductionVoiding cystourethrogram (VCUG) provides a wealth of data on urinary tract function and anatomy, but few standards exist for reporting VCUG findings.ObjectiveWe aimed to assess variability in VCUG reports and to test our hypothesis that VCUG reports from pediatric facilities and pediatric radiologists are more complete than those performed at other facilities or by non-pediatric radiologists.Study designWe analyzed original VCUG reports from children enrolled in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial. A 23-item checklist was created and used to evaluate reporting of technical (e.g. catheter size), anatomic (e.g. vesicoureteral reflux (VUR) presence and grade, bladder shape), and functional information (e.g. bladder emptying). Radiologists were classified as pediatric or non-pediatric radiologists. Facilities were categorized as to whether they were a freestanding pediatric hospital (FSPH), a pediatric "hospital within a hospital" (PHWH), a non-pediatric hospital (NPH), or an outpatient radiology facility (ORF). Multivariate linear regression was used to analyze factors associated with the completeness of the VCUG reports (percent of items reported from the 23-item checklist).ResultsSix-hundred and two VCUGs were performed at 90 institutions. Of those, 76% were read by a pediatric radiologist, and 49% were performed at a FSPH (Table). On average, less than half of the 23 items in our standardized assessment tool were included in VCUG reports (mean 48%, SD 12). The completeness of reports varied by facility type: 51% complete at FSPH (SD 11), 50% at PHWH (SD 10), 36% at NPH (SD 11), and 43% at ORF (SD 8) (p < 0.0001). In multivariate analysis, VCUG reports generated at NPH or ORF had 8% fewer items included (95% CI 3.0-12.8, p < 0.01), and those generated at PHWH did not differ from those generated at FSPH. Reports read by a non-pediatric radiologist had 6% fewer items included (95% CI 3-9.7; p < 0.01) compared with those read by a pediatric radiologist.DiscussionThere is substantial underreporting of findings in VCUG reports when assessing a widely represented sample of routine, community-generated reports using an idealized standard. Although VUR was often reported, other crucial anatomic and functional findings of the VCUG were consistently underreported across all facility types.ConclusionAlthough pediatric radiologist and pediatric hospitals generated more complete VCUG reports compared with those having non-pediatric origins, the differences are small when considering the substantial underreporting of VCUG findings in general. This underscores the opportunities for improvement in reporting of VCUG findings.

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II1 Apr 2017MP11-12 ANTIMICROBIAL PROPHYLAXIS FOR TRANSRECTAL ULTRASOUND GUIDED PROSTATE BIOPSY: A PROSPECTIVE COHORT TRIAL Teresa Zembower, Kelly Maxwell, Robert Nadler, John Cashy, Marc Scheetz, Chao Qi, and Anthony J. Schaeffer Teresa ZembowerTeresa Zembower More articles by this author , Kelly MaxwellKelly Maxwell More articles by this author , Robert NadlerRobert Nadler More articles by this author , John CashyJohn Cashy More articles by this author , Marc ScheetzMarc Scheetz More articles by this author , Chao QiChao Qi More articles by this author , and Anthony J. SchaefferAnthony J. Schaeffer More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.413AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We evaluated the effectiveness of targeted antimicrobial prophylaxis in men undergoing transrectal ultrasound guided prostate biopsy (TRUSP). METHODS A prospective, non-randomized cohort study evaluated targeted prophylaxis to determine the rate of post-biopsy infectious complications. Rectal swab cultures plated on selective media identified ciprofloxacin-resistant and-susceptible gram-negative bacteria (CR-GNB and CS-GNB). Patients with CS-GNB received ciprofloxacin while those with CR-GNB received directed prophylaxis. Infectious complications were defined clinically and microbiologically within 30 days after TRUSP. RESULTS Between November 1, 2012 and March 31, 2015, 510 men completed the study; 430 (84.3%) harbored CS-GNB, 80 (15.7%) CR-GNB and 76 (95%) CR-GNB were Escherichia coli. 484 (94.9%) completed the study per protocol, while 26 (5.1%) who received dual prophylaxis were evaluated in a separate intention-to-treat analysis. Of the 484, 475 (98.1%) had no infections, while 9 (1.9%) experienced clinical infections and 6 (1.2%) were culture-proven (CP). The infections included uncomplicated UTIs n=5 (1.0 %), 4 CP (0.8%); complicated UTIs n=1 (0.2%); and urosepsis, n=3 (0.6 %), 1 CP (0.2%). The 5 patients with uncomplicated UTIs were managed as outpatients, whereas the 4 with complicated UTIs or sepsis were admitted to the hospital for a mean of 2.6 days. All recovered without sequelae. No drug-related adverse events occurred. CONCLUSIONS Targeted antimicrobial prophylaxis achieved a low rate of infectious complications, limited morbidity and no sustained sequelae. These results were based on individual rectal flora cultures, suggesting that similar results can be obtained in a variety of patients, settings and over time. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e141 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Teresa Zembower More articles by this author Kelly Maxwell More articles by this author Robert Nadler More articles by this author John Cashy More articles by this author Marc Scheetz More articles by this author Chao Qi More articles by this author Anthony J. Schaeffer More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II1 Apr 2017MP82-04 TRANSCRIPTIONAL REGULATION OF CORTICOTROPIN RELEASING FACTOR Lizath Aguiniga, Anthony Schaeffer, and David Klumpp Lizath AguinigaLizath Aguiniga More articles by this author , Anthony SchaefferAnthony Schaeffer More articles by this author , and David KlumppDavid Klumpp More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2551AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Interstitial cystitis (IC) patients suffer from chronic pelvic pain and bladder dysfunction. IC patients have altered cortisol levels suggesting dysregulation of the hypothalamic-pituitary adrenal (HPA) axis and suffer from exacerbated symptoms in response to high stress. Corticotropin-releasing factor (CRF) is the initiator of the HPA axis and mediates stress responses and voiding control, where increased CRF levels in Barrington's nucleus induce bladder dysfunction. Arachidonic acid (AA) metabolites have been shown to induce CRF expression, however the transcriptional mediators of this modulation are unknown. Here we identify transcription factors that mediate AA-induced CRF gene expression. METHODS We used MIRAGE software to identify candidate transcription factor binding sites in a 1kb region of the human CRF gene promoter. We identified a peroxisome proliferator activated hormone response element (PPRE) and two Xenobiotic Responsive Element (XRE) sites as candidate mediators of AA-dependent CRF induction. Site-directed mutations of the PPRE and XRE sites were generated in a CRF-luciferase reporter plasmid to evaluate responses to AA and the impact of AhR and PPAR gamma expressed in HEK 293T cells. The hypothalamic neuronal cell line N42 was used to evaluate the role of AhR and PPAR gamma in native promoter regulation by RT PCR. We also generated mice that have PPAR gamma and AhR knocked-out in CRF-expressing cells and characterized voiding activity. RESULTS AA induction in the PPRE mutant resulted in increased CRF promoter activity compared to WT, whereas XRE1 had decreased activity. The mutation of both XRE1 and XRE2 resulted in decreased responsiveness to AA. Over-expression of PPAR gamma alone showed no change, while over-expression of AhR alone showed a significant increase in AA-induced CRF expression; this was inhibited by over-expression of both AhR and PPAR gamma in HEK 293T cells. Over-expression of AhR in N42 cells resulted in increased CRF mRNA in response to AA induction. AhR conditional knockout mice showed increased voiding frequency. CONCLUSIONS These results suggest AhR binding to the XRE sites modulates AA-dependent CRF gene expression. PPAR gamma inhibits AA-dependent CRF gene expression. Continued studies will use mouse models to examine the in vivo role of AhR and PPAR gamma inhibitors to modulate voiding activity. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1098 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Lizath Aguiniga More articles by this author Anthony Schaeffer More articles by this author David Klumpp More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I1 Apr 2017MP85-20 ACYLOXYACYL HYDROLASE MODULATES PELVIC PAIN SEVERITY Wenbin Yang, Ryan Yaggie, Mingcheng Jiang, Charles Rudick, Joseph Done, Charles Heckman, Anthony Schaeffer, and David Klumpp Wenbin YangWenbin Yang More articles by this author , Ryan YaggieRyan Yaggie More articles by this author , Mingcheng JiangMingcheng Jiang More articles by this author , Charles RudickCharles Rudick More articles by this author , Joseph DoneJoseph Done More articles by this author , Charles HeckmanCharles Heckman More articles by this author , Anthony SchaefferAnthony Schaeffer More articles by this author , and David KlumppDavid Klumpp More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2682AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Chronic pelvic pain causes significant morbidity to patients and is a bane to clinicians. Using a murine neurogenic cystitis model that recapitulates key aspects of interstitial cystitis/bladder pain syndrome (IC), we recently showed that pseudorabies virus (PRV) induces severe pelvic allodynia BALB/c mice, relative to C57BL/6 mice. Here, we use a genetic strategy to identify a novel modulator of pelvic pain expressed along the bladder-brain axis. METHODS Mouse SNP genotyping: We generated 96 F2 female mice, infected with PRV, and pelvic pain was scored in response to von Frey filament stimulus. Purified F2 mouse tail DNA was genotyped with Illumina Mouse MD arrays containing 1449 SNPs. We mapped QTL using R/qtl software. Knockout mice were evaluated for pelvic allodynia, and expression was localized by immunofluorescence. RESULTS female F1CxB mice exhibit the low-allodynia phenotype of C57BL/6 parental mice in response to PRV, indicating that the severe pelvic pain phenotype of BALB/c mice is recessive. To identify loci modulating pelvic pain, we performed a quantitative trait locus (QTL) analysis on female F2CxB progeny by quantifying PRV-induced allodynia and statistical associations between pelvic pain and recombinant genotypes. Analyses identified a polymorphism on chromosome 13, rs6314295, significantly associated with allodynia (LOD=3.11). Expression analyses revealed that the mouse gene for acyloxyacyl hydrolase (AOAH), encoded near this SNP, was induced in the sacral spinal cord of PRV-infected mice. AOAH-deficient mice exhibited pelvic hypersensitivity compared to wild-type (WT) mice and developed extreme pelvic allodynia both in neurogenic and bacterial cystitis models. AOAH deficiency results in greater bladder pathology in neurogenic cystitis consistent with increased bladder mast cell activation. AOAH expression was detected along the bladder-brain axis, and AOAH-deficient mice have elevated levels of bladder VEGF, a UCPPS biomarker. CONCLUSIONS These findings indicate that AOAH is expressed along the bladder-brain axis and modulates pelvic pain severity and UCPPS biomarker expression. Thus, allelic variation in Aoah may mediate susceptibility to UCPPS symptoms. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1155 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Wenbin Yang More articles by this author Ryan Yaggie More articles by this author Mingcheng Jiang More articles by this author Charles Rudick More articles by this author Joseph Done More articles by this author Charles Heckman More articles by this author Anthony Schaeffer More articles by this author David Klumpp More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

IntroductionVoiding cystourethrography (VCUG) is the modality of choice to diagnose vesicoureteral reflux (VUR). Although grading of VUR is essential for prognosis and clinical decision-making, the inter-observer reliability for grading has been shown to vary substantially. The Randomized Intervention for Children with VesicoUreteral Reflux (RIVUR) trial provides a large cohort of children with VUR to better understand the reliability of VCUG findings.ObjectiveTo determine the inter-observer consistency of the grade of VUR and other VCUG findings in a large cohort of children with VUR.Study designThe RIVUR trial is a randomized controlled trial of antimicrobial prophylaxis in children with VUR diagnosed after UTI. Each enrollment VCUG was read by a local clinical (i.e. non-reference) radiologist, and independently by two blinded RIVUR reference radiologists. Reference radiologists' disagreements were adjudicated for trial purposes. The grade of VUR and other VCUG findings were extracted from the local clinical radiologist's report. The unit of analysis included individual ureters and individual participants. We compared the three interpretations for grading of VUR and other VCUG findings to determine the inter-observer reliability. ResultsSix-hundred and two non-reference radiology reports from 90 institutions were reviewed and yielded the grade of VUR for 560 left and 524 right ureters. All three radiologists agreed on VUR grade in only 59% of ureters; two of three agreed on 39% of ureters; and all three disagreed on 2% of ureters (Table). Agreement was better (>= 92%) for other VCUG findings (e.g. bladder shape "normal"). The non-reference radiologists' grade of VUR differed from the reference radiologists' adjudicated grade by exactly one grade level in 19% of ureters, and by two or more grade levels in 2.2% of ureters. When the participant was the unit of analysis, all three radiologists agreed on the grade of VUR in both ureters in just 43% of cases. Discussion Our study shows considerable and clinically relevant variability in grading VUR by VCUG. This variability was consistent when comparing non-reference to the adjudicated reference radiologists' assessment and the reference radiologists to each other. This study was limited to children with a history of UTI and grade I-IV VUR and may not be generalizable to all children who have a VCUG.ConclusionThe considerable inter-observer variability in VUR grading has both research and clinical implications, as study design, risk stratification, and clinical decision-making rely heavily on grades of VUR.

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I1 Apr 2016MP24-15 CLINICALLY DIVERSE LPS ISOLATES DIRECTLY STIMULATE DRG NEURONS: RELEVANCE FOR BLADDER PAIN Abdel Belmadani, Richard Miller, Rachel Miller, Anne-Marie Malfait, Ryan Yaggie, Anthony Schaeffer, and David Klumpp Abdel BelmadaniAbdel Belmadani More articles by this author , Richard MillerRichard Miller More articles by this author , Rachel MillerRachel Miller More articles by this author , Anne-Marie MalfaitAnne-Marie Malfait More articles by this author , Ryan YaggieRyan Yaggie More articles by this author , Anthony SchaefferAnthony Schaeffer More articles by this author , and David KlumppDavid Klumpp More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.771AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES E. coli evoke a spectrum of pain responses when instilled into the bladder, ranging from no pelvic pain to post-UTI chronic pain that persists after transient infection. Previous studies indicate that E. coli-induced pain is mediated by TLR4 independent of inflammation. Because TLR4 activation is associated with TRPV1-mediated calcium responses in DRG neurons, we evaluated the hypothesis that differential bacterial pain phenotypes correlate with LPS-induced responses of DRG neurons. METHODS LPS was purified from E. coli strains NU14, Sf874, and 83972, representing bacterial pain phenotypes of acute, chronic, and analgesic, respectively. Responses of intact murine DRGs to LPS were quantified by monitoring (Ca2+) in using PIRT-GCamP3 ratiometric Ca imaging imaging using spinning disk confocal microscopy. GCamP3 is expressed in all DRG neurons in these mice. Effects of LPS isolates on production of the proalgogenic chemokine MCP-1 by cultured DRG neurons was also measured. RESULTS All LPS isolates induced robust MCP-1 secretion in dissociated cultures of DRG neurons that was not influenced by bacterial pain phenotypes. All LPS isolates were also capable of producing robust (Ca2+) in signals in capsaicin sensitive DRG neurons in whole ganglia. Sf874 LPS increased (Ca2+) in less frequently than the other isolates investigated. CONCLUSIONS Compared to our prior observations that MCP-1 expression in intact DRG in vivo responses vary with E. coli pain phenotypes in an MCP-1 reporter mouse, these data suggest that DRG MCP-1 responses vary between dissociated and intact preparations suggesting a role for non-neuronal cells. Calcium imaging supports the idea that LPS can directly activate DRG neurons. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e275 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Abdel Belmadani More articles by this author Richard Miller More articles by this author Rachel Miller More articles by this author Anne-Marie Malfait More articles by this author Ryan Yaggie More articles by this author Anthony Schaeffer More articles by this author David Klumpp More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

OBJECTIVE:To determine the mean and normal range of anteroposterior diameter (APD) of the renal pelves in children.METHODS:Patients aged 0-19 years with normal spinal MRIs were identified after institutional review board approval. Those with dilating uropathy or abdominal surgery/radiation were excluded. The maximum APD was measured. A mixed linear model was fit to determine the relationship between APD and age, adjusted for bladder distention. The left and right kidneys were treated independently.RESULTS:283 left and 285 right renal units were included. For the left, a 3.5% increase in APD per year was predicted (p < 0.0001), with the average APD for infants and 18-year olds with non-distended bladders being 2.5 mm (95th percentile: 7.2 mm) and 4.6 mm (13.4 mm), respectively. For the right, a 3.9% increase in APD per year was predicted (p < 0.0001), with the average APD for infants and 18-year olds with non-distended bladders being 2.8 mm (8.4 mm) and 5.5 mm (16.6 mm), respectively. Compared with a non-distended bladder, a distended bladder increased the predicted APD between 23% (right) and 38% (left) (p = 0.01 and p < 0.0001, respectively).CONCLUSION:The mean and normal ranges of APD measured by MRI in children are provided. APD increases with age and bladder distension and is greater on the left. Advances in knowledge: This article establishes normative ranges for APD, a critical component of genitourinary tract evaluation, and does so using the most precise imaging modality for this condition.

Uropathogenic Escherichia coli (UPEC) accounts for 80 to 90% of urinary tract infections (UTI), and the increasing rate of antibiotic resistance among UPEC isolates reinforces the need for vaccines to prevent UTIs and recurrent infections. Previous studies have shown that UPEC isolate NU14 suppresses proinflammatory NF-κB-dependent cytokines (D. J. Klumpp, A. C. Weiser, S. Sengupta, S. G. Forrestal, R. A. Batler, and A. J. Schaeffer, Infect Immun 69:6689-6695, 2001, http://dx.doi.org/10.1128/IAI.69.11.6689-6695.2001; B. K. Billips, A. J. Schaeffer, and D. J. Klumpp, Infect Immun 76:3891-3900, 2008, http://dx.doi.org/10.1128/IAI.00069-08). However, modification of lipopolysaccharide (LPS) structure by deleting the O-antigen ligase gene (waaL) enhanced proinflammatory cytokine secretion. Vaccination with the ΔwaaL mutant diminished NU14 reservoirs and protected against subsequent infections. Therefore, we hypothesized that LPS structural determinants shape immune responses. We evaluated the contribution of LPS domains to urovirulence corresponding to the inner core (waaP, waaY, and rfaQ), outer core (rfaG), and O-antigen (waaL, wzzE, and wzyE). Deletion of waaP, waaY, and rfaG attenuated adherence to urothelial cells in vitro In a murine UTI model, the ΔrfaG mutant had the most severe defect in colonization. The mutation of rfaG, waaL, wzzE, and wzyE resulted in an inability to form reservoirs in mouse bladders. Infection with the LPS mutant panel resulted in various levels of urinary myeloperoxidase. Since the ΔwaaL mutant promoted Th1-associated adaptive responses in previous studies (B. K. Billips, R. E. Yaggie, J. P. Cashy, A. J. Schaeffer, and D. J. Klumpp, J Infect Dis 200:263-272, 2009, http://dx.doi.org/10.1086/599839), we assessed NU14 for Th2-associated cytokines. We found NU14 infection stimulated TLR4-dependent bladder interleukin-33 (IL-33) production. Inoculation with rfaG, waaL, wzzE, and wzyE mutants showed decreased IL-33 production. We quantified antigen-specific antibodies after infection and found significantly increased IgE and IgG1 in ΔwaaP mutant-infected mice. Our studies show LPS structural constituents mediate multiple aspects of the UPEC life cycle, including the ability to acutely colonize bladders, form reservoirs, and evoke innate and adaptive immune responses.

The article by Eisenberg et al (1Eisenberg M.L. Li S. Cullen M.R. Baker L.C. Increased risk of incident chronic medical conditions in infertile men: Analysis of US claims data.Fertil Stert. 2016; 105: 629-636Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar) is an important salvo in the body of literature linking male infertility to broader somatic health using claims data. Significant prior work done in this area has linked male infertility to increased cancer risk (2Walsh T.J. Schembri M. Turek P.J. Chan J.M. Carroll P.R. Smith J.F. et al.Increased risk of high-grade prostate cancer among infertile men.Cancer. 2010; 116: 2140-2147PubMed Google Scholar), cardiovascular mortality (3Eisenberg M.L. Park Y. Hollenbeck A.R. Lipshultz L.I. Schatzkin A. Pletcher M.J. Fatherhood and the risk of cardiovascular mortality in the NIH-AARP Diet and Health Study.Hum Reprod. 2011; 26: 3479-3485Crossref PubMed Scopus (42) Google Scholar), and has suggested that cohorts of infertile men may not represent the general US population (4Hotaling J.M. Davenport M.T. Eisenberg M.L. VanDenEeden S.K. Walsh T.J. Men who seek infertility care may not represent the general U.S. population: data from the National Survey of Family Growth.Urology. 2012; 79: 123-127Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar). Although other investigators have used claims data to examine the association between male infertility and cancer and overall mortality, investigations into the association between reproductive and somatic health are limited by the lack of datasets that capture the outpatient nature of the diagnosis and longitudinal follow-up needed to identify systemic disease (5Brooke B.S. Goodney P.P. Kraiss L.W. Gottlieb D.J. Samore M.H. Finlayson S.R. Readmission destination and risk of mortality after major surgery: an observational cohort study.Lancet. 2015; 386: 884-895Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar). Before discussing the article, we would like to review the cohort and findings of the study, because they are complex.This retrospective cohort study by Eisenberg et al. (1Eisenberg M.L. Li S. Cullen M.R. Baker L.C. Increased risk of incident chronic medical conditions in infertile men: Analysis of US claims data.Fertil Stert. 2016; 105: 629-636Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar) uses the Truven Health MarketScan Commercial Claims and Encounters database to examine the association between male infertility, defined as a diagnosis of male infertility by International Classification of Diseases, 9th revision (ICD-9) code 606.x, and the outcome of various ICD-9–defined comorbidities including cardiovascular disease, peripheral vascular disease, hyperlipidemia, hypertension, chronic obstructive pulmonary disease, liver disease, renal disease, anxiety disorders, bipolar disorder, and depression. They also chose to look at such behavioral issues as alcohol and drug abuse. Subjects must have visited a physician 1 year before and after the diagnosis, and were also excluded if they had a cancer or medical diagnosis before or within 1 year of their infertility diagnosis. This inpatient and outpatient database of more than 70 million privately insured individuals (including 15 million reproductive-aged male lives) allowed for the identification of 13,027 men with a diagnosis of male infertility and 23,860 with a diagnosis of fertility testing. This cohort had a total follow-up time of 42,478 years or over 3 years per individual, on average. The authors also compared this with a cohort of 79,099 vasectomized men.The authors used a Cox proportional hazards model comparing men diagnosed with male infertility with men simply tested for infertility, and they determined that the male infertility group had an increased risk of many of the outcomes of interest, including a 30% and 50% increased risk of diabetes and ischemic heart disease, respectively. Additionally, azoospermic men were found to have a higher incidence of renal disease and alcohol abuse, although this could be due to reverse causality (e.g., renal disease causing infertility).Although the methods are rigorous and the results are provocative, this study must be interpreted cautiously. Besides the interesting choice to look at behavioral patterns associated with infertility, there are three reasons why these results must be validated in future studies: the number of subjects defined as having infertility is much lower than expected, the comparison group (infertility testing) is likely to contain many infertile men, and the short follow-up introduces the potential for the outcomes existing at the time of the fertility diagnosis or reverse causality (the outcome causing infertility). However, the fact that the comparison group (infertility testing) is likely subfertile or infertile actually would tend to strengthen the results of this study. Much like nearly all the work done in this area, the length of follow-up for these men is likely not sufficient to disentangle the reverse causality and ensure that the men were followed long enough to develop systemic disease that was not pre-existing at the time of fertility testing.The first and most significant issue is the lower than expected number of infertile males. Using their inclusion criteria, the authors identify infertility in less than 1% of the nearly 15 million males aged 18–50 years. If we assume that 15% of couples are infertile, and that half of this is due to male factor, 7% of males have some degree of male factor. Thus, 10 million men in this cohort aged 18–50 would translate into 700,000 men with male infertility (as compared with the nearly 37,000 men considered infertile using the authors' coding criteria). This is explained by several factors. Much of this may be due to lack of care seeking. Thirty-year-old men are known to seek care much less often than similarly aged women. However, this is likely not the only reason accounting for the drastically lower number of expected subjects. More likely is the authors coding scheme that underrepresents the number of infertile men in the sample, which is the second major limitation. The authors have done an excellent job dealing with this, and this bias is, sadly, inherent in all claims-based analyses of male reproduction.The vast majority of reproductive urologists will intentionally not code a patient for male infertility, in an attempt to garner some coverage for the encounter. Although most insurance providers will cover the diagnostic workup of male infertility, very few cover treatments. Thus, many providers will code a man as being "at risk for hypogonadism" or "rule out testicular failure" rather than male infertility. Further, few providers will change the diagnosis from infertility testing to male infertility once a patient is diagnosed with male infertility. For these reasons, it is very likely that many comparator men who received fertility testing are infertile and should have been counted as such. If we assume that many "fertile" men in this report were in fact infertile, then the authors might have underreported the effect size. This limitation will be very difficult to overcome with claims data such as these that fail to capture semen analyses and other biologic markers at a very granular level.Finally, the concept of reverse causation could in fact lead to incorrect interpretation of the results. Reverse causality is when an outcome precedes or causes the exposure. An example of reverse causation is that of alcoholism leading to mental illness. This conclusion is based on the assumption that mental illness does not lead to alcoholism, which is not true. As it pertains to this report, the authors allow for the outcome to be coded as soon as 1 year after the infertility diagnosis. Without allowing for 3 or 4 years between index diagnosis and outcome, the possibility exists that infertility and the outcomes of interest could have been occurring together. A short average follow up time introduces the possibility that reverse causation is occurring. How would the results differ if the outcome was coded 3 years after the infertility diagnosis?This works lays the foundation for further analyses in this area, which are vital to cementing the concept that a man's reproductive potential can serve as a biomarker for his somatic health. The article by Eisenberg et al (1Eisenberg M.L. Li S. Cullen M.R. Baker L.C. Increased risk of incident chronic medical conditions in infertile men: Analysis of US claims data.Fertil Stert. 2016; 105: 629-636Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar) is an important salvo in the body of literature linking male infertility to broader somatic health using claims data. Significant prior work done in this area has linked male infertility to increased cancer risk (2Walsh T.J. Schembri M. Turek P.J. Chan J.M. Carroll P.R. Smith J.F. et al.Increased risk of high-grade prostate cancer among infertile men.Cancer. 2010; 116: 2140-2147PubMed Google Scholar), cardiovascular mortality (3Eisenberg M.L. Park Y. Hollenbeck A.R. Lipshultz L.I. Schatzkin A. Pletcher M.J. Fatherhood and the risk of cardiovascular mortality in the NIH-AARP Diet and Health Study.Hum Reprod. 2011; 26: 3479-3485Crossref PubMed Scopus (42) Google Scholar), and has suggested that cohorts of infertile men may not represent the general US population (4Hotaling J.M. Davenport M.T. Eisenberg M.L. VanDenEeden S.K. Walsh T.J. Men who seek infertility care may not represent the general U.S. population: data from the National Survey of Family Growth.Urology. 2012; 79: 123-127Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar). Although other investigators have used claims data to examine the association between male infertility and cancer and overall mortality, investigations into the association between reproductive and somatic health are limited by the lack of datasets that capture the outpatient nature of the diagnosis and longitudinal follow-up needed to identify systemic disease (5Brooke B.S. Goodney P.P. Kraiss L.W. Gottlieb D.J. Samore M.H. Finlayson S.R. Readmission destination and risk of mortality after major surgery: an observational cohort study.Lancet. 2015; 386: 884-895Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar). Before discussing the article, we would like to review the cohort and findings of the study, because they are complex. This retrospective cohort study by Eisenberg et al. (1Eisenberg M.L. Li S. Cullen M.R. Baker L.C. Increased risk of incident chronic medical conditions in infertile men: Analysis of US claims data.Fertil Stert. 2016; 105: 629-636Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar) uses the Truven Health MarketScan Commercial Claims and Encounters database to examine the association between male infertility, defined as a diagnosis of male infertility by International Classification of Diseases, 9th revision (ICD-9) code 606.x, and the outcome of various ICD-9–defined comorbidities including cardiovascular disease, peripheral vascular disease, hyperlipidemia, hypertension, chronic obstructive pulmonary disease, liver disease, renal disease, anxiety disorders, bipolar disorder, and depression. They also chose to look at such behavioral issues as alcohol and drug abuse. Subjects must have visited a physician 1 year before and after the diagnosis, and were also excluded if they had a cancer or medical diagnosis before or within 1 year of their infertility diagnosis. This inpatient and outpatient database of more than 70 million privately insured individuals (including 15 million reproductive-aged male lives) allowed for the identification of 13,027 men with a diagnosis of male infertility and 23,860 with a diagnosis of fertility testing. This cohort had a total follow-up time of 42,478 years or over 3 years per individual, on average. The authors also compared this with a cohort of 79,099 vasectomized men. The authors used a Cox proportional hazards model comparing men diagnosed with male infertility with men simply tested for infertility, and they determined that the male infertility group had an increased risk of many of the outcomes of interest, including a 30% and 50% increased risk of diabetes and ischemic heart disease, respectively. Additionally, azoospermic men were found to have a higher incidence of renal disease and alcohol abuse, although this could be due to reverse causality (e.g., renal disease causing infertility). Although the methods are rigorous and the results are provocative, this study must be interpreted cautiously. Besides the interesting choice to look at behavioral patterns associated with infertility, there are three reasons why these results must be validated in future studies: the number of subjects defined as having infertility is much lower than expected, the comparison group (infertility testing) is likely to contain many infertile men, and the short follow-up introduces the potential for the outcomes existing at the time of the fertility diagnosis or reverse causality (the outcome causing infertility). However, the fact that the comparison group (infertility testing) is likely subfertile or infertile actually would tend to strengthen the results of this study. Much like nearly all the work done in this area, the length of follow-up for these men is likely not sufficient to disentangle the reverse causality and ensure that the men were followed long enough to develop systemic disease that was not pre-existing at the time of fertility testing. The first and most significant issue is the lower than expected number of infertile males. Using their inclusion criteria, the authors identify infertility in less than 1% of the nearly 15 million males aged 18–50 years. If we assume that 15% of couples are infertile, and that half of this is due to male factor, 7% of males have some degree of male factor. Thus, 10 million men in this cohort aged 18–50 would translate into 700,000 men with male infertility (as compared with the nearly 37,000 men considered infertile using the authors' coding criteria). This is explained by several factors. Much of this may be due to lack of care seeking. Thirty-year-old men are known to seek care much less often than similarly aged women. However, this is likely not the only reason accounting for the drastically lower number of expected subjects. More likely is the authors coding scheme that underrepresents the number of infertile men in the sample, which is the second major limitation. The authors have done an excellent job dealing with this, and this bias is, sadly, inherent in all claims-based analyses of male reproduction. The vast majority of reproductive urologists will intentionally not code a patient for male infertility, in an attempt to garner some coverage for the encounter. Although most insurance providers will cover the diagnostic workup of male infertility, very few cover treatments. Thus, many providers will code a man as being "at risk for hypogonadism" or "rule out testicular failure" rather than male infertility. Further, few providers will change the diagnosis from infertility testing to male infertility once a patient is diagnosed with male infertility. For these reasons, it is very likely that many comparator men who received fertility testing are infertile and should have been counted as such. If we assume that many "fertile" men in this report were in fact infertile, then the authors might have underreported the effect size. This limitation will be very difficult to overcome with claims data such as these that fail to capture semen analyses and other biologic markers at a very granular level. Finally, the concept of reverse causation could in fact lead to incorrect interpretation of the results. Reverse causality is when an outcome precedes or causes the exposure. An example of reverse causation is that of alcoholism leading to mental illness. This conclusion is based on the assumption that mental illness does not lead to alcoholism, which is not true. As it pertains to this report, the authors allow for the outcome to be coded as soon as 1 year after the infertility diagnosis. Without allowing for 3 or 4 years between index diagnosis and outcome, the possibility exists that infertility and the outcomes of interest could have been occurring together. A short average follow up time introduces the possibility that reverse causation is occurring. How would the results differ if the outcome was coded 3 years after the infertility diagnosis? This works lays the foundation for further analyses in this area, which are vital to cementing the concept that a man's reproductive potential can serve as a biomarker for his somatic health. Increased risk of incident chronic medical conditions in infertile men: analysis of United States claims dataFertility and SterilityVol. 105Issue 3PreviewTo determine the incidence of chronic medical conditions of men with infertility. Full-Text PDF

You have accessJournal of UrologyPediatrics1 Apr 2015V7-04 MULTI-INSTITUTIONAL BLADDER EXSTROPHY CONSORTIUM: COMPLETE PRIMARY REPAIR OF EXSTROPHY Joseph G. Borer, Evalynn Vasquez, Anthony J. Schaeffer, Douglas A. Canning, John V. Kryger, and Michael E. Mitchell Joseph G. BorerJoseph G. Borer More articles by this author , Evalynn VasquezEvalynn Vasquez More articles by this author , Anthony J. SchaefferAnthony J. Schaeffer More articles by this author , Douglas A. CanningDouglas A. Canning More articles by this author , John V. KrygerJohn V. Kryger More articles by this author , and Michael E. MitchellMichael E. Mitchell More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1935AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES For bladder exstrophy (BE) repair, gaining necessary surgical experience is challenging due to the rarity of BE. We created a multi-institutional collaboration for the purposes of sharing collective expertise, to efficiently maximize surgical proficiency, and to standardize surgical technique and subsequent care of complete primary repair of exstrophy (CPRE). Our objective is to demonstrate the surgical technique adopted by this collaboration. METHODS Boston Children's Hospital, Children's Hospital of Philadelphia and Children's Hospital of Wisconsin alternately served as host site for scheduled surgeries, with observation, commentary and critique by surgeons from the other sites. Technique was CPRE with bilateral iliac osteotomy performed at 1-3 months of age. Video recording was used for real-time observation both locally and remotely, teaching, future analysis, editing, and review. RESULTS From February 2013 through September 2014, CPRE was performed in 23 patients: 12 boys and 8 girls with classic bladder exstrophy; 1 boy and 2 girls with epispadias. Three surgical modifications were adopted by the group. The first concerned approach to the urethral plate dissection in the boy. The current approach uses a ventral dissection along the medial aspect of the corpora cavernosa using bipolar electrocautery. The second was the deliberate attempt to form a bladder neck in an effort to increase continence by elongating the urethra and creating a more acutely angled transition from proximal urethra to bladder neck into bladder. The third was made after urethral obstruction was noted in 3 girls. Preplacement of perineal and urethral meatus sutures prior to approximation of the pubis allowed optimal exposure of the tissue for accurate and precise suture placement. Complications in girls included 4 episodes of pyelonephritis, 3 urethral obstructions (1 resulted in bladder rupture and 2 required temporary clean intermittent catheterization), and 1 partial labial separation. Complications in boys included 3 urethrocutaneous fistula, 1 hypospadias, return to operating room for 1 suprapubic tube removal, and 1 spica cast change. All closures were successful without dehiscence. CONCLUSIONS We report the surgical method adopted by a multi-institutional collaboration. The increased volume of patients, expert opinions shared, and proficiency gained were immediate benefits observed. This effort increased the annual experience of each institution involved from 3 to 9-fold to ultimately benefit patient care. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e660 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joseph G. Borer More articles by this author Evalynn Vasquez More articles by this author Anthony J. Schaeffer More articles by this author Douglas A. Canning More articles by this author John V. Kryger More articles by this author Michael E. Mitchell More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Purpose of review Recurrent urinary tract infection (rUTI) is a serious clinical problem, yet effective therapeutic options are limited, especially against multidrug-resistant uropathogens. In this review, we explore the development of a clinically relevant model of rUTI in previously infected mice and review recent developments in bladder innate immunity that may affect susceptibility to rUTI. Recent findings Chronic bladder inflammation during prolonged bacterial cystitis in mice causes bladder mucosal remodelling that sensitizes the host to rUTI. Although constitutive defenses help prevent bacterial colonization of the urinary bladder, once infection occurs, induced cytokine and myeloid cell responses predominate and the balance of immune cell defense and bladder immunopathology is critical for determining disease outcome, in both naïve and experienced mice. In particular, the maintenance of the epithelial barrier appears to be essential for preventing severe infection. Summary The innate immune response plays a key role in determining susceptibility to rUTI. Future studies should be directed towards understanding how the innate immune response changes as a result of bladder mucosal remodelling in previously infected mice, and validating these findings in human clinical specimens. New therapeutics targeting the immune response should selectively target the induced innate responses that cause bladder immunopathology, while leaving protective defenses intact.

You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Prostate & Genitalia1 Apr 2015MP25-06 MODELS OF LOWER URINARY TRACT SYMPTOMS IN THE PRESENCE AND ABSENCE OF PAIN Daniel J. Mazur, Anthony J. Schaeffer, and Praveen Thumbikat Daniel J. MazurDaniel J. Mazur More articles by this author , Anthony J. SchaefferAnthony J. Schaeffer More articles by this author , and Praveen ThumbikatPraveen Thumbikat More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1209AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a debilitating condition characterized mainly by pelvic pain. In addition, many patients report voiding complaints and lower urinary tract symptoms (LUTS). While the mechanism behind these voiding complaints is not well understood, it is possible that inflammation induces fibrosis within the prostate, as has been hypothesized to occur in benign prostatic hyperplasia (BPH). To better understand this process, we developed two transient infection-induced prostatitis murine models where LUTS can be studied in the presence or absence of chronic pain. METHODS C57BL/6 (B6) and NOD/ShiLtJ (NOD) mice (5-7 weeks old) were transurethrally infected with Escherichia coli strain CP-1, a bacteria from a CP/CPPS patient that clears from the prostate and bladder of mice by 30 days. At post-infection days 5, 14, and 35, the mice were pain tested for referred pain with von-Frey filaments and the prostates and bladders harvested for analysis (4-8 mice per time point). Additionally, urodynamic evaluation was completed at day 35 under urethane anesthesia. Prostate and bladder specimens were analyzed by flow cytometry and real-time quantitative PCR (QT-PCR) for the presence of cells and markers involved in fibrosis. RESULTS B6 mice did not develop pain, however, NOD mice developed significant pain at all time points. Cystometry showed increased frequency of bladder contractions in CP-1 infected mice of both strains. By flow cytometry, B6 mice developed an increase in fibrocytes (vimentin+, CD45+) in the prostate at day 14 which became statistically significant at day 35. A similar but delayed trend was noted in NOD mice with an increase in fibrocytes at day 35, however, this was not statistically significant. NOD mice did develop a significant increase in vimentin+ cells (mesenchymal cells) at day 14. The bladders of B6 mice demonstrated a significant increase in vimentin+ cells at day 35 and at day 14 in the NOD mice. There was no difference in the presence of fibrocytes in the bladders. B6 mice had a >1 fold increase in expression of collagen 1a1, 1a2, αSMA, and CXCL5 at day 14 by QT-PCR. A similar increase in these markers was noted in the NOD mice but at the earlier time point of day 5. CONCLUSIONS We have demonstrated in infection-induced prostatitis murine models that urinary frequency develops in the presence and absence of pain. This is associated with the concurrent suggestion of fibrosis within the prostate, with altered kinetics of development in each model. Further studies are underway to identify the pathogenesis of LUTS in the context of inflammation and pain. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e287 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel J. Mazur More articles by this author Anthony J. Schaeffer More articles by this author Praveen Thumbikat More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...