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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 Δ waaL 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 Δ rfaG 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 Δ waaL mutant promoted Th 1 -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 Th 2 -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 Δ waaP 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.

Clinical phenotyping of urological chronic pelvic pain syndromes (UCPPSs) in men and women have focused on end organ abnormalities to identify putative clinical subtypes. Initial evidence of abnormal brain function and structure in male pelvic pain has necessitated large-scale, multisite investigations into potential UCPPS brain biomarkers. We present the first evidence of regional white matter (axonal) abnormalities in men and women with UCPPS, compared with positive (irritable bowel syndrome, IBS) and healthy controls. Epidemiological and neuroimaging data were collected from participants with UCPPS (n = 52), IBS (n = 39), and healthy sex- and age-matched controls (n = 61). White matter microstructure, measured as fractional anisotropy (FA), was examined by diffusion tensor imaging. Group differences in regional FA positively correlated with pain severity, including segments of the right corticospinal tract and right anterior thalamic radiation. Increased corticospinal FA was specific and sensitive to UCPPS, positively correlated with pain severity, and reflected sensory (not affective) features of pain. Reduced anterior thalamic radiation FA distinguished patients with IBS from those with UCPPS and controls, suggesting greater microstructural divergence from normal tract organization. Findings confirm that regional white matter abnormalities characterize UCPPS and can distinguish between visceral diagnoses, suggesting that regional axonal microstructure is either altered with ongoing pain or predisposes its development.

Purpose: Lower urinary tract symptoms are a common finding in patients with chronic prostatitis/chronic pelvic pain syndrome. We previously reported that the mast cell-tryptase-PAR2 (protease activated receptor 2) axis has a critical role in the development of chronic pain in experimental autoimmune prostatitis, a mouse model of chronic prostatitis/chronic pelvic pain syndrome. Therefore, we examined whether PAR2 activation mediates lower urinary tract dysfunction.Materials and Methods: Functional cystometry was done in male B6 mice along with immunoblotting and immunohistochemistry for the expression of COL1A1 (collagen type I α I) and α-SMA (α-smooth muscle actin). Flow cytometry analysis was performed on single cell suspensions of the prostate, bladder, lymph nodes and spleen.Results: Experimental autoimmune prostatitis resulted in increased urinary voiding frequency and decreased bladder capacity 30 days after initiation. Concurrently, there was increased expression of COL1A1 and α-SMA in the prostate...

Summary 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. Summary Table . Excerpts of Qualitative Analysis of 30 children with UI. Impacts and Adaptations Representative Quotes (Participant ID) Practical affects Sleepovers I don't do sleepovers anymore because I don't want to risk [an accident] (F) Sports If I have an accident while I'm doing a sport, it might interfere, because if I can't get changed and washed up because there's no bathroom nearby … (N) Emotional Impact Negative Embarrassment Well it's embarrassing, and it's uncomfortable … The smell, I really hate the smell, and I would get embarrassed about it … I feel embarrassed. I feel disappointed in myself. I feel like I've failed (L) Anxiety If it's a really long car ride, then … I get kind of scared that I'm going to have to go pee and there's going to be nowhere we can stop (J) Shame It makes you feel like you're different. You're not like they are; you're different. You're not at the same level they are; you're under them somewhere … It's kind of like knowing that you're hiding this really ugly secret that you don't want anybody to find out … It's been a struggle. It almost makes me feel kind of childish in a way (H) Adaptations Preventative Don't hold it in … Even if you don't have to go, go to the bathroom, and that will prevent you from having accidents (O) Mitigating At home, I'll change. But if I'm at recess, or something, I'll tie my sweatshirt around me, or if I don't have a sweatshirt, I'll try to cover it with my shirt, sometimes, until we get inside, because I always carry around some pads and a change of underwear in my bag (P)

Background Prostatic inflammation is a key contributor to lower urinary tract symptoms (LUTS). An intraurethral infection with a uropathogenic isolate of E. coli (CP1) results in clinical signs of benign prostatic hyperplasia (BPH) and LUTS as demonstrated by increased urinary dysfunction, prostate inflammation and fibrosis. In this study we study the importance of mast cells in driving prostate inflammation in BPH/LUTS and the therapeutic benefit of mast cell neutralization on the disease. Results We observed increased mast cell infiltration and activation associated with increased fibrosis in prostate tissues from BPH patients and CP1 infected mice as identified by toluidine blue and picrosirius staining. To assess the role of mast cell activation, inhibition was performed using a combination of a mast cell stabilizer and histamine 1 receptor (H1R) antagonist at an early and late time point post CP1 infection. Treatment with this combination resulted in a decrease of activated mast cells in prostate tissues of infected mice. Furthermore, the prostate of these mice showed decreased prostate fibrosis and inflammation as assessed by picrosirius red staining and flow cytometry for immune cell infiltrates. Finally, we observed that this combination treatment can ameliorate the urinary dysfunction previously observed in response to CP1 infection, as assessed using unconscious terminal cystometry and bladder voiding function measurements. Conclusions These results provide evidence of the critical role played by mast cells in the development of prostate inflammation in BPH/LUTS. A combination therapy of mast cell stabilizer and H1R antagonist maybe a useful target for therapeutic intervention in men with BPH/LUTS.

INTRODUCTION AND OBJECTIVE:Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating condition of chronic pelvic pain. We previously linked a locus encoding acyloxyacyl hydrolase (Aoah)...

INTRODUCTION AND OBJECTIVE:Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition of chronic pelvic pain often co-morbid with voiding dysfunction and depression. We have p...

Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) is a common syndrome with limited therapies and an unknown etiology. Previously, our laboratory has defined a potential role for pathogenic infection in disease onset. Intra-urethral infection with a uropathogenic Escherichia coli strain isolated from a CP/CPPS patient, CP1, induces prostatic inflammation and tactile allodynia in mice. We have also demonstrated that a prostate specific Staphylococcus epidermidis bacterial isolate, NPI (non-pain inducing), from a healthy subject reduces pain and inflammation in an experimental autoimmune prostatitis (EAP) murine model. Here we focus on the interplay between these human isolates in the context of prostatitis development and resolution. NOD/ShiLtJ mice were inoculated with either NP1 or CP1, or combinations of both. Infection with CP1 induced pelvic tactile allodynia after 7 days, while NPI instillation alone induced no such response. Instillation with NPI 7 days following CP1 infection resolved pelvic tactile allodynia and prophylactic instillation 7 days prior to CPI infection prevented its onset. Prophylactic NPI instillation also prevented CP1 colonization of both prostate and bladder tissues. In vitro analyses revealed that CP1 and NPI do not directly inhibit the growth or invasive potential of one another. Immunological analyses revealed that specific markers associated with CP1-induced pelvic allodynia were decreased upon NPI treatment or repressed by prophylactic colonization. This study demonstrates that a commensal bacterial isolate can inhibit the colonization, pain responses, and immunological activation to uropathogenic bacteria, emphasizing the power of a healthy prostatic microflora in controlling health and disease.

Introduction Chronic pelvic pain syndrome (CPPS) is a complex disorder that affects a large proportion of all men. A limited understanding of its etiology and pathogenesis is reflected by the absence of effective therapies. Although CPPS is deemed clinically non-infectious with no well-defined etiological role for microbes, bacteria is readily isolated from both healthy and patient prostate secretion and urine samples. Our laboratory has previously demonstrated that a specific gram-negative bacterial isolate can induce CPPS-like symptoms in mice. Here we aimed to expand on these findings examining the role of gram-positive patient-derived bacteria in CPPS. Methods A retrospective analysis of bacterial cultures from CPPS patients from a single center was performed. Gram-positive bacteria were isolated from the expressed prostatic secretion (EPS) of three CPPS-patients (pain inducers, PI) and one from a healthy volunteer (non-pain inducer, NPI). These bacteria were inoculated intra-urethrally in two mouse backgrounds and analyzed for their ability to induce tactile allodynia, voiding dysfunction, and colonize the murine prostate. Host immune responses to bacterial instillation were analyzed by flow cytometry. Results PI strains (Staphylococcus haemolyticus 2551, Enterococcus faecalis 427, and Staphylococcus epidermidis 7244) induced and maintained tactile allodynia responses (200% increase above baseline) for 28 days in NOD/ShiLtJ mice. Conversely the healthy subject derived strain (Staphylococcus epidermidis NPI) demonstrated no significant pelvic allodynia induction. Intra-urethral inoculation of the four bacterial strains into C57BL/6 mice did not induce significant increases in pain responses. Infected NOD/ShiLtJ displayed significant voiding dysfunction compared to their control counterparts. Colony counts of prostate tissues from both NOD/ShiLtJ and C57BL/6 mice at day 28 demonstrated that bacterial strains colonized equally well, including NPI. We also determined that mechanistically, the patient-isolates induced prostate inflammation specifically involving T-cells and monocytes. Conclusions Gram-positive isolates from CPPS patients showed enhanced ability to induce tactile allodynia compared to a single taxonomically similar gram-positive strain isolated from a healthy control. Responses were shown to be dependent on host genetic background and not on colonization differences between strains.

Bacteriuria during pregnancy may be classified as asymptomatic bacteriuria, infections of the lower urinary tract (cystitis), or infections of the upper urinary tract (pyelonephritis). Lower tract bacteriuria is associated with an increased risk of developing pyelonephritis in pregnancy, which is itself associated with adverse maternal and fetal outcomes. Pregnant women should be screened for the presence of bacteriuria early in pregnancy. All bacteriuria in pregnancy should be treated, and antimicrobial choice in pregnancy should reflect safety for both the mother and the fetus. After treatment of bacteriuria, patients should be followed closely due to risk of recurrent bacteriuria.

© 2015 American Urological Association Education and Research, Inc. Purpose: Several chronic pain conditions may be distinguished by condition specific brain anatomical and functional abnormalities on imaging, which are suggestive of underlying disease processes. We present what is to our knowledge the first characterization of interstitial cystitis/bladder pain syndrome associated white matter (axonal) abnormalities based on multicenter neuroimaging from the MAPP Research Network. Materials and Methods: We assessed 34 women with interstitial cystitis/bladder pain syndrome and 32 healthy controls using questionnaires on pain, mood anddaily function. White matter microstructure was evaluated by diffusion tensor imaging to model directional water flow along axons or fractional anisotropy. Regions correlating with clinical parameters were further examined for gender and syndrome dependence. Results: Women with interstitial cystitis/bladder pain syndrome showed numerous white matter abnormalities that correlated with pain severity, urinary symptoms and impaired quality of life. Interstitial cystitis/bladder pain syndrome was characterized by decreased fractional anisotropy in aspects of the right anterior thalamic radiation, the left forceps major and the right longitudinal fasciculus. Increased fractional anisotropy was detected in the right superior and bilateral inferior longitudinal fasciculi. Conclusions: To our knowledge we report the first characterization of brain white matter abnormalities in women with interstitial cystitis/bladder pain syndrome. Regional decreases and increases in white matter integrity across multiple axonal tracts were associated with symptom severity. Given that white matter abnormalities closely correlated with hallmark symptoms of interstitial cystitis/bladder pain syndrome, including bladder pain and urinary symptoms, brain anatomical alterations suggest that there are neuropathological contributions to chronic urological pelvic pain.

Purpose: We used MAPP data to identify participants with urological chronic pelvic pain syndromes only or a chronic functional nonurological associated somatic syndrome in addition to urological chronic pelvic pain syndromes. We characterized these 2 subgroups and explored them using 3 criteria, including 1) MAPP eligibility criteria, 2) self-reported medical history or 3) RICE criteria.Materials and Methods: Self-reported cross-sectional data were collected on men and women with urological chronic pelvic pain syndromes, including predominant symptoms, symptom duration and severity, nonurological associated somatic syndrome symptoms and psychosocial factors.Results: Of 424 participants with urological chronic pelvic pain syndromes 162 (38%) had a nonurological associated somatic syndrome, including irritable bowel syndrome in 93 (22%), fibromyalgia in 15 (4%), chronic fatigue syndrome in 13 (3%) and multiple syndromes in 41 (10%). Of 233 females 103 (44%) had a nonurological associated somatic syndrome co...

Inflammation is associated with several diseases of the prostate including benign enlargement and cancer, but a causal relationship has not been established. Our objective was to characterize the prostate inflammatory microenvironment after infection with a human prostate-derived bacterial strain and to determine the effect of inflammation on prostate cancer progression. To this end, we mimicked typical human prostate infection with retrograde urethral instillation of CP1, a human prostatic isolate of Escherichia coli. CP1 bacteria were tropic for the accessory sex glands and induced acute inflammation in the prostate and seminal vesicles, with chronic inflammation lasting at least 1 year. Compared to controls, infection induced both acute and chronic inflammation with epithelial hyperplasia, stromal hyperplasia, and inflammatory cell infiltrates. In areas of inflammation, epithelial proliferation and hyperplasia often persist, despite decreased expression of androgen receptor (AR). Inflammatory cells in the prostates of CP1-infected mice were characterized at 8 weeks post-infection by flow cytometry, which showed an increase in macrophages and lymphocytes, particularly Th17 cells. Inflammation was additionally assessed in the context of carcinogenesis. Multiplex cytokine profiles of inflamed prostates showed that distinct inflammatory cytokines were expressed during prostate inflammation and cancer, with a subset of cytokines synergistically increased during concurrent inflammation and cancer. Furthermore, CP1 infection in the Hi-Myc mouse model of prostate cancer accelerated the development of invasive prostate adenocarcinoma, with 70% more mice developing cancer by 4.5 months of age. This study provides direct evidence that prostate inflammation accelerates prostate cancer progression and gives insight into the microenvironment changes induced by inflammation that may accelerate tumour initiation or progression.

Chronic pelvic pain causes significant patient morbidity and is a challenge 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 in BALB/c mice relative to C57BL/6 mice. Here, we report that a quantitative trait locus (QTL) analysis of PRV-induced allodynia in F2CxBprogeny identified a polymorphism on chromosome 13, rs6314295 , significantly associated with allodynia (logarithm of odds = 3.11). The nearby gene encoding acyloxyacyl hydrolase ( Aoah) was induced in the sacral spinal cord of PRV-infected mice. AOAH-deficient mice exhibited increased vesicomotor reflex in response to bladder distension, consistent with spontaneous bladder hypersensitivity, and increased pelvic allodynia in neurogenic cystitis and postbacterial chronic pain models. AOAH deficiency resulted in greater bladder pathology and tumor necrosis factor production in PRV neurogenic cystitis, markers of increased bladder mast cell activation. AOAH immunoreactivity was detectable along the bladder-brain axis, including in brain sites previously correlated with human chronic pelvic pain. Finally, AOAH-deficient mice had significantly higher levels of bladder vascular endothelial growth factor, an emerging marker of chronic pelvic pain in humans. These findings indicate that AOAH modulates pelvic pain severity, suggesting that allelic variation in Aoah influences pelvic pain in IC.

Chronic pain is often measured with a severity score that overlooks its spatial distribution across the body. This widespread pain is believed to be a marker of centralization, a central nervous system process that decouples pain perception from nociceptive input. Here, we investigated whether centralization is manifested at the level of the brain using data from 1079 participants in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network (MAPP) study. Participants with a clinical diagnosis of urological chronic pelvic pain syndrome (UCPPS) were compared to pain-free controls and patients with fibromyalgia, the prototypical centralized pain disorder. Participants completed questionnaires capturing pain severity, function, and a body map of pain. A subset (UCPPS N = 110; fibromyalgia N = 23; healthy control N = 49) underwent functional and structural magnetic resonance imaging. Patients with UCPPS reported pain ranging from localized (pelvic) to widespread (throughout the body). Patients with widespread UCPPS displayed increased brain gray matter volume and functional connectivity involving sensorimotor and insular cortices (P < 0.05 corrected). These changes translated across disease diagnoses as identical outcomes were present in patients with fibromyalgia but not pain-free controls. Widespread pain was also associated with reduced physical and mental function independent of pain severity. Brain pathology in patients with centralized pain is related to pain distribution throughout the body. These patients may benefit from interventions targeting the central nervous system.

BACKGROUND The pathogenesis of chronic prostatitis/chronic pelvic pain syndrome is unknown and factors including the host's immune response and the nervous system have been attributed to the development of CP/CPPS. We previously demonstrated that mast cells and chemokines such as CCL2 and CCL3 play an important role in mediating prostatitis. Here, we examined the role of neuroinflammation and microglia in the CNS in the development of chronic pelvic pain. METHODS Experimental autoimmune prostatitis (EAP) was induced using a subcutaneous injection of rat prostate antigen. Sacral spinal cord tissue (segments S14–S5) was isolated and utilized for immunofluorescence or QRT-PCR analysis. Tactile allodynia was measured at baseline and at various points during EAP using Von Frey fibers as a function for pelvic pain. EAP mice were treated with minocycline after 30 days of prostatitis to test the efficacy of microglial inhibition on pelvic pain. RESULTS Prostatitis induced the expansion and activation of microglia and the development of inflammation in the spinal cord as determined by increased expression levels of CCL3, IL-1β, Iba1, and ERK1/2 phosphorylation. Microglial activation in mice with prostatitis resulted in increased expression of P2X4R and elevated levels of BDNF, two molecular markers associated with chronic pain. Pharmacological inhibition of microglia alleviated pain in mice with prostatitis and resulted in decreased expression of IL-1β, P2X4R, and BDNF. CONCLUSION Our data show that prostatitis leads to inflammation in the spinal cord and the activation and expansion of microglia, mechanisms that may contribute to the development and maintenance of chronic pelvic pain. Prostate 75:50–59, 2015. © 2014 Wiley Periodicals, Inc.

The cause of chronic pelvic pain syndrome (CPPS) has yet to be established. Since the late 1980s, cytokine, chemokine, and immunological classification studies using human samples have focused on identifying biomarkers for CPPS, but no diagnostically beneficial biomarkers have been identified, and these studies have done little to deepen our understanding of the mechanisms underlying chronic prostatic pain. Given the large number of men thought to be affected by this condition and the ineffective nature of current treatments, there is a pressing need to elucidate these mechanisms. Prostatitis types IIIa and IIIb are classified according to the presence of pain without concurrent presence of bacteria; however, it is becoming more evident that, although levels of bacteria are not directly associated with levels of pain, the presence of bacteria might act as the initiating factor that drives primary activation of mast-cell-mediated inflammation in the prostate. Mast cell activation is also known to suppress regulatory T cell (Treg) control of self-tolerance and also activate neural sensitization. This combination of established autoimmunity coupled with peripheral and central neural sensitization can result in the development of multiple symptoms, including pelvic pain and bladder irritation. Identifying these mechanisms as central mediators in CPPS offers new insight into the prospective treatment of the disease.

Objective: To review the classification, evaluation, and management of pediatric urinary incontinence. Methods: An examination of texts and peer-reviewed literature was performed to identify subject matter relevant to the stated objectives, with the experience of the senior author used in cases where the literature failed to provide guidance. Results: On the basis of our review, we identified the International Children’s Continence Society’s (ICCS) statement standardizing the terminology for lower urinary tract function in children and present a logical classification scheme for incontinence. After an epidemiology review, we discuss the appropriate evaluation of the incontinent child, of which the cornerstones are a detailed history and thorough physical exam. Finally, a concise discussion of the management of daytime incontinence, nocturnal enuresis, and neurogenic and anatomic incontinence is presented, with deference to evidence-based approaches where available. Depending on the type of incontinence, the management strategies can include behavioral, pharmacologic, and/or surgical approaches. Conclusion: Pediatric urinary incontinence is a common condition which, after appropriate evaluation, can be successfully treated. Keywords : Urinary incontinence; Diurnal enuresis; Nocturnal enuresis; Pediatrics

We determined whether including a care coordination system to manage the referral process for hematuria would lead to improved quality of care.Inflection Navigator, a protocol based, electronic medical record enabled care coordination system, was developed to support primary care physicians evaluating newly discovered hematuria. We studied the system for patients referred for microscopic and gross hematuria from May 2009 to May 2010. We compared outcomes in these 106 patients and in 105 referred to our urology department for hematuria during the same period who did not use the system.Patients in the care coordination group completed the evaluation in a significantly shorter time with more than a 1-month difference in time between referral and the completion of the imaging and cystoscopy components of the assessment (mean 40.9 vs 74.1 days, p0.05). This system potentially lowered health care costs by decreasing the mean ± SD number of urology visits needed to complete an evaluation from 2.1 ± 1.5 in the standard referral group to 1.6 ± 1.4 in the care coordination group (p0.05).A protocol based care coordination system for hematuria decreased the time needed to complete an evaluation and decreased the number of overall visits required to make a final diagnosis. Thus, the Inflection Navigator system is an example of an electronic medical record enabled process innovation that can improve the efficiency of care while potentially lowering health care costs.

Objective To ascertain cystoscope durability in relation to usage and cost in the outpatient setting. Methods Six flexible cystoscopes were provided to our outpatient clinic by 2 vendors. Five Wolf 7305.006S02 cystoscopes (Richard Wolf Medical Instruments Corporation, Vernon Hills, IL) and 1 Olympus CYF-5 (Olympus America, Center Valley, PA) were used 2477 times over a 14-month study period. Prospective data were accumulated on each cystoscope including type of procedure, number of uses until mechanical failure, physician usage, and maintenance costs. All staff was trained in proper handling and maintenance of cystoscopes utilizing an Occupational Safety and Health Administration (OSHA) approved protocol. Retrospective comparison was performed of 1346 cystoscopic procedures during the previous 8 months before implementation of the processing protocol, with data including type and quantity of mechanical failures along with maintenance costs. Results Five total study period failures occurred in 4 cystoscopes, with a mean of 495.4 procedures/failure. In 3 separate cystoscopes, failure occurred after 70 (perforation of working channel), 194 (leak in bending rubber), and 236 uses (hole in bending rubber). One cystoscope had 2 failures after 168 (cut in bending rubber) and 255 uses (failed leak test). During the retrospective period, there were 10 failures, with a mean of 134.6 procedures/failure. Four failures were secondary to crushed insertion tubes. Comparison of retrospective and study period costs revealed a 43.9% decrease from $9.64 per procedure to $5.41 per procedure. Conclusion Outpatient flexible cystoscope durability seems directly related to optimization of handling and storage of cystoscopes. Costs related to mechanical failure were reduced with a rigorous reprocessing protocol.

To determine the mean and normal range of anteroposterior diameter (APD) of the renal pelves in children.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.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).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.

Summary Introduction Voiding cystourethrogram (VCUG) provides a wealth of data on urinary tract function and anatomy, but few standards exist for reporting VCUG findings. Objective We 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 design We 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 free-standing 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). Results Six-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 p p Discussion There 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. Conclusion Although 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. Table . Summary of population and results. Characteristic No. of VCUG reports analyzed 602 Gender of participants Male 49 (8.1%) Female 553 (91.9%) Median age in months at VCUG (IQR) 11 (5,30) VCUG read by a Pediatric radiologist 459 (76.2%) Non-pediatric radiologist 134 (22.3%) VCUG performed at b FSPH 297 (49.3%) PHWH 184 (30.6%) NPF 87 (14.5%) ORF 33 (5.5%) Overall frequency of item being reported (8 items selected from 23 total) Indication from procedure 557 (93) Presence of VUR 601 (99) Grade of VUR 585 (97) Cyclic study 95 (16) Complete bladder emptying 429 (71) Bladder appearance 517 (86) Urethra appearance 447 (74) Delayed images assessing upper tracts 151 (25) FSPH = free-standing pediatric hospital; NPH = non-pediatric hospital; ORF = outpatient radiology facility; PHWH = pediatric ‘hospital within a hospital’; VCUG = voiding cystourethrogram; VUR = vesicoureteral reflex. a Nine reports lacked information to identify the radiologist. b One facility type was unknown.

PURPOSE: We compared demographic and clinical characteristics of the University of Sciences Malaysia Chronic Prostatitis Cohort to the United States National Institutes of Health Chronic Prostatitis Cohort. MATERIALS AND METHODS: Participants met the same definition of chronic prostatitis/chronic pelvic pain syndrome. Each participant had extensive demographic, medical history, previous treatment, clinical and laboratory evaluations. RESULTS: The University of Sciences Malaysia and National Institutes of Health cohorts proved similar in most respects. National Institutes of Health-Chronic Prostatitis Symptom Index total scores, pain and urinary subscores were similar for the 332 University of Sciences Malaysia Chronic Prostatitis Cohort and 488 National Institutes of Health Chronic Prostatitis Cohort participants. Differences included worse quality of life subscore for the University of Sciences Malaysia Chronic Prostatitis Cohort, differences in the location, number of sites, and types of pain/discomfort between the 2 populations, and that the University of Sciences Malaysia participants had received less previous treatment. CONCLUSIONS: The demographic characteristics and clinical presentation of chronic prostatitis/chronic pelvic pain syndrome proved remarkably similar in these diverse populations. Both cohorts experienced major reduction in their quality of life from chronic pelvic pain and urinary symptoms. Comparison of diverse populations using standard clinical, laboratory and assessment instruments is feasible, and may provide important insights into chronic prostatitis/chronic pelvic pain syndrome and the factors that determine clinical outcome.

Interstitial cystitis/bladder pain syndrome (IC) is associated with significant morbidity, yet underlying mechanisms and diagnostic biomarkers remain unknown. Pelvic organs exhibit neural crosstalk by convergence of visceral sensory pathways, and rodent studies demonstrate distinct bacterial pain phenotypes, suggesting that the microbiome modulates pelvic pain in IC. Stool samples were obtained from female IC patients and healthy controls, and symptom severity was determined by questionnaire. Operational taxonomic units (OTUs) were identified by16S rDNA sequence analysis. Machine learning by Extended Random Forest (ERF) identified OTUs associated with symptom scores. Quantitative PCR of stool DNA with species-specific primer pairs demonstrated significantly reduced levels of E. sinensis, C. aerofaciens, F. prausnitzii, O. splanchnicus, and L. longoviformis in microbiota of IC patients. These species, deficient in IC pelvic pain (DIPP), were further evaluated by Receiver-operator characteristic (ROC) analyses, and DIPP species emerged as potential IC biomarkers. Stool metabolomic studies identified glyceraldehyde as significantly elevated in IC. Metabolomic pathway analysis identified lipid pathways, consistent with predicted metagenome functionality. Together, these findings suggest that DIPP species and metabolites may serve as candidates for novel IC biomarkers in stool. Functional changes in the IC microbiome may also serve as therapeutic targets for treating chronic pelvic pain.

We examined symptom variability in men and women with urological chronic pelvic pain syndrome. We describe symptom fluctuations as related to early symptom regression and its effect on estimated 1-year symptom change. We also describe a method to quantify patient specific symptom variability.Symptoms were assessed biweekly in 424 subjects with urological chronic pelvic pain syndrome during 1 year. To evaluate the impact of early symptom regression subjects were classified as improved, no change or worse according to the rate of change using 1) all data, 2) excluding week 0 and 3) excluding weeks 0 and 2. Patient specific, time varying variability was calculated at each interval using a sliding window approach. Patients were classified as high, medium or low variability at each time and ultimately as high or low variability overall based on the variability for the majority of contacts.Prior to excluding early weeks to adjust for early symptom regression 25% to 38% and 5% to 6% of patients were classified as improved and worse, respectively. After adjustment the percent of patients who were improved or worse ranged from 15% to 25% and 6% to 9%, respectively. High and low variability phenotypes were each identified in 25% to 30% of participants.Patients with urological chronic pelvic pain syndrome show symptom variability. At study enrollment patients had worse symptoms on average, resulting in a regression effect that influenced the estimated proportion of those who were improved or worse. Prospective studies should include a run-in period to account for regression to the mean and other causes of early symptom regression. Further, symptom variability may be quantified and used to characterize longitudinal symptom profiles of urological chronic pelvic pain syndrome.

Purpose Successful primary bladder closure of classic bladder exstrophy sets the stage for development of adequate bladder capacity and eventual voided continence. The postoperative pathway following primary bladder closure at the authors’ institution is quantitatively and qualitatively detailed. Materials and methods Sixty-five consecutive newborns (47 male) undergoing primary closure of classic bladder exstrophy were identified and data were extracted relating to immediate postoperative care. Overall success rate was utilized to validate the pathway. Results Mean age at time of primary closure was 4.6 days and mean hospital stay was 35.8 days. Osteotomy was performed in 19 patients (mean age 8.8 days), and was not required in 39 infants (mean age 2.9 days). All patients were immobilized for 4 weeks. Tunneled epidural analgesia was employed in 61/65 patients. All patients had ureteral catheters and a suprapubic tube, along with a comprehensive antibiotic regimen. Postoperative total parenteral nutrition was commonly administered, and enteral feedings started around day 4.6. Our success rate of primary closure was 95.4%. Conclusions A detailed and regimented plan for bladder drainage, immobilization, pain control, nutrition, antimicrobial prophylaxis, and adequate healing time is a cornerstone for the postoperative management of the primary closure of bladder exstrophy.

We evaluated targeted antimicrobial prophylaxis in men undergoing transrectal ultrasound guided prostate biopsy based on rectal swab culture results.From July 2010 to March 2011 we studied differences in infectious complications in men who received targeted vs standard empirical ciprofloxacin prophylaxis before transrectal ultrasound guided prostate biopsy. Targeted prophylaxis used rectal swab cultures plated on selective media containing ciprofloxacin to identify fluoroquinolone resistant bacteria. Patients with fluoroquinolone susceptible organisms received ciprofloxacin while those with fluoroquinolone resistant organisms received directed antimicrobial prophylaxis. We identified men with infectious complications within 30 days after transrectal ultrasound guided prostate biopsy using the electronic medical record.A total of 457 men underwent transrectal ultrasound guided prostate biopsy, and of these men 112 (24.5%) had rectal swab obtained while 345 (75.5%) did not. Among those who received targeted prophylaxis 22 (19.6%) men had fluoroquinolone resistant organisms. There were no infectious complications in the 112 men who received targeted antimicrobial prophylaxis, while there were 9 cases (including 1 of sepsis) among the 345 on empirical therapy (p=0.12). Fluoroquinolone resistant organisms caused 7 of these infections. The total cost of managing infectious complications in patients in the empirical group was $13,219. The calculated cost of targeted vs empirical prophylaxis per 100 men undergoing transrectal ultrasound guided prostate biopsy was $1,346 vs $5,598, respectively. Cost-effectiveness analysis revealed that targeted prophylaxis yielded a cost savings of $4,499 per post-transrectal ultrasound guided prostate biopsy infectious complication averted. Per estimation, 38 men would need to undergo rectal swab before transrectal ultrasound guided prostate biopsy to prevent 1 infectious complication.Targeted antimicrobial prophylaxis was associated with a notable decrease in the incidence of infectious complications after transrectal ultrasound guided prostate biopsy caused by fluoroquinolone resistant organisms as well as a decrease in the overall cost of care.

The reasons for referral and treatment strategies in patients who underwent complete primary repair of bladder exstrophy elsewhere in the newborn period were evaluated.An institutionally approved database identified patients who underwent complete primary repair of exstrophy and were subsequently referred for continued care.A total of 10 females and 55 males were referred for treatment between 1996 and 2010. Six females and 23 males were referred for complications following initial complete primary repair of exstrophy. Female complications included dehiscence (3 patients), prolapse (2) and stricture (1). Male complications included dehiscence (10 patients), prolapse (9), pubic separation (1) and stricture (3). Nine males had posterior urethral loss and 13 had major penile soft tissue injuries. Grade V vesicoureteral reflux and severe hydronephrosis were seen in the 4 patients with urethral strictures. Patients with dehiscence or prolapse underwent successful reclosure with osteotomy. Cases with posterior urethral loss or strictures were repaired with grafts. Four females and 32 males were referred for incontinence. Nine of these patients had poor bladder capacity, of whom 5 underwent bladder augmentation with continent stoma and 4 are awaiting further bladder growth. A total of 27 patients underwent bladder neck repair, with 15 (56%) subsequently continent, 5 (19%) daytime continent with nocturnal incontinence and 7 (26%) continuously incontinent. At initial closure osteotomy had been performed in all patients who were continent following bladder neck reconstruction and in 4 of 5 who were daytime continent.Complications of complete primary repair of bladder exstrophy can result in undesired upper urinary tract changes and penile soft tissue loss. Surgical reconstruction of such complications and acceptable continence are attainable in select cases.

Research into the pathophysiology of chronic prostatitis/chronic pelvic pain syndrome has primarily focused on markers of peripheral dysfunction. We present the first neuroimaging investigation to our knowledge to characterize brain function and anatomy in chronic prostatitis/chronic pelvic pain syndrome.We collected data from 19 male patients with chronic prostatitis/chronic pelvic pain syndrome, and 16 healthy age and gender matched controls. Functional magnetic resonance imaging data were obtained from 14 patients with chronic prostatitis/chronic pelvic pain syndrome as they rated spontaneous pain inside the scanner. Group differences (16 patients per group) in gray matter total volume and regional density were evaluated using voxel-based morphometry, and white matter integrity was studied with diffusion tensor imaging to measure fractional anisotropy. Functional and anatomical imaging outcomes were correlated with the clinical characteristics of chronic prostatitis/chronic pelvic pain syndrome.Spontaneous pelvic pain was uniquely characterized by functional activation within the right anterior insula, which correlated with clinical pain intensity. No group differences were found in regional gray matter volume, yet density of gray matter in pain relevant regions (anterior insula and anterior cingulate cortices) positively correlated with pain intensity and extent of pain chronicity. Moreover the correlation between white matter anisotropy and neocortical gray matter volume was disrupted in chronic prostatitis/chronic pelvic pain syndrome.We provide novel evidence that the pain of chronic prostatitis/chronic pelvic pain syndrome is associated with a chronic pelvic pain syndrome specific pattern of functional brain activation and brain anatomical reorganization. These findings necessitate further investigations into the role of central mechanisms in the initiation and maintenance of chronic prostatitis/chronic pelvic pain syndrome.

A Panel of International Experts was convened by the Infectious Diseases Society of America (IDSA) in collaboration with the European Society for Microbiology and Infectious Diseases (ESCMID) to update the 1999 Uncomplicated Urinary Tract Infection Guidelines by the IDSA. Co-sponsoring organizations include the American Congress of Obstetricians and Gynecologists, American Urological Association, Association of Medical Microbiology and Infectious Diseases–Canada, and the Society for Academic Emergency Medicine. The focus of this work is treatment of women with acute uncomplicated cystitis and pyelonephritis, diagnoses limited in these guidelines to premenopausal, non-pregnant women with no known urological abnormalities or co-morbidities. The issues of in vitro resistance prevalence and the ecological adverse effects of antimicrobial therapy (collateral damage) were considered as important factors in making optimal treatment choices and thus are reflected in the rankings of recommendations.

Peyronie disease (PD) arises from the deposition of collagen and fibrin that creates a plaque in the tunica albuginea of the penis. The resulting induration and curvature of the penis leads to sexual dysfunction in many men. Despite the prevalence of the disease and natural history studies that suggest progression, men might not seek therapeutic intervention due to a lack of general knowledge about the disease, its pathophysiology, and treatments aimed at ameliorating its symptoms. Medical therapy using oral, topical, or intralesionally delivered drug is pursued in all but the most severe cases. This review of the literature in the last 4 years attempts to identify new trials of therapies and treatment modalities aimed at altering the PD process. Specifically, we will address clinical trials evaluating oral pharmacotherapies; topical, intralesional, and shockwave therapies; and penile traction devices. We will discuss the level of evidence and support for each of the new clinical trials.

Urinary tract infection (UTI) is the most common extraintestinal infectious disease entity in women worldwide, and perhaps one of the most formidable challenges in clinical practice given its high prevalence, frequent recurrence, and myriad associated morbidities in the setting of rapidly evolving antimicrobial resistance. Achieving timely symptom relief and infection control and preventing morbidity, growth of resistant organisms, and recurrent infection are often difficult. This article reviews epidemiology and pathogenesis of urinary tract infection in women; characterizes common patterns of infection, clinical red flags, and appropriate laboratory testing and imaging; explores emerging patterns of antimicrobial resistance; and reviews the updated guidelines for the treatment of uncomplicated UTI in women.

In the past numerous chemokines have been noted in the expressed prostatic secretions of patients with chronic prostatitis/chronic pelvic pain syndrome. We examined the functional effects of chemokines in expressed prostatic secretions of patients with chronic pelvic pain syndrome.We studied the functional effects of expressed prostatic secretions on human monocytes by examining monocyte chemotaxis in response to monocyte chemoattractant protein-1, a major chemoattractant previously identified in chronic prostatitis/chronic pelvic pain syndrome cases. We determined effects on cellular signaling by quantifying intracellular calcium increase in monocytes and nuclear factor-κB activation in normal prostate epithelial cells.Results show that the monocyte chemoattractant protein-1 in expressed prostatic secretions is nonfunctional with an inability to mediate human monocyte chemotaxis, or mediate signaling in monocytes or prostate epithelial cells. This lack of functionality could be extended to other proinflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α, when incubated with expressed prostatic secretions from patients with chronic pelvic pain syndrome. The mechanism underlying this apparent ability to modulate proinflammatory cytokines involves heat labile extracellular proteases that mediate the inhibition of immune and prostate epithelial cell function.These results may have implications for the design of specific diagnostic and therapeutic methods targeted toward the complete resolution of prostate inflammatory insults.

Background Pelvic pain is a major component of the morbidity associated with urinary tract infection (UTI), yet the molecular mechanisms underlying UTI-induced pain remain unknown. UTI pain mechanisms likely contrast with the clinical condition of asymptomatic bacteriuria (ASB), where individuals have significant bacterial loads yet lack symptoms.

The overlap of pain and urinary voiding symptoms is common for urologic patients. The etiology of these syndromes is frequently multifactorial and due to disorders of the bladder and/or prostate. The evaluation and treatment of these syndromes continues to evolve. Here we summarize the general approach to evaluation and treatment of these pain syndromes.