Purpose: This document seeks to establish guidance for the evaluation and management of women with recurrent urinary tract infections (rUTI) to prevent inappropriate use of antibiotics, decrease the risk of antibiotic resistance, reduce adverse effects of antibiotic use, provide guidance on antibiotic and nonantibiotic strategies for prevention, and improve clinical outcomes and quality of life by reducing recurrence of urinary tract infection (UTI) events. Materials and Methods: The systematic review utilized to inform this guideline was conducted by a methodology team at the Pacific Northwest Evidence-based Practice Center. A research librarian conducted searches in Ovid MEDLINE (1946 to January Week 1 2018), Cochrane Central Register of Controlled Trials (through December 2017) and Embase (through January 16, 2018). An update literature search was conducted on September 20, 2018. Results: When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low). Such evidence-based statements are provided as Strong, Moderate, or Conditional Recommendations. In instances of insufficient evidence, additional guidance is provided as Clinical Principles and Expert Opinions. Conclusions: Our ability to diagnose, treat, and manage rUTI long-term has evolved due to additional insights into the pathophysiology of rUTI, a new appreciation for the adverse effects of repetitive antimicrobial therapy, rising rates of bacterial antimicrobial resistance (AMR), and better reporting of the natural history and clinical outcomes of acute cystitis and rUTI. As new data continue to emerge in this space, this document will undergo review to ensure continued accuracy.

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Introduction and hypothesis To evaluate the evidence for pathologies underlying stress urinary incontinence (SUI) in women. Methods For the data sources, a structured search of the peer-reviewed literature (English language; 1960–April 2020) was conducted using predefined key terms in PubMed and Embase. Google Scholar was also searched. Peer-reviewed manuscripts that reported on anatomical, physiological or functional differences between females with signs and/or symptoms consistent with SUI and a concurrently recruited control group of continent females without any substantive urogynecological symptoms. Of 4629 publications screened, 84 met the inclusion criteria and were retained, among which 24 were included in meta-analyses. Results Selection bias was moderate to high; < 25% of studies controlled for major confounding variables for SUI (e.g., age, BMI and parity). There was a lack of standardization of methods among studies, and several measurement issues were identified. Results were synthesized qualitatively, and, where possible, random-effects meta-analyses were conducted. Deficits in urethral and bladder neck structure and support, neuromuscular and mechanical function of the striated urethral sphincter (SUS) and levator ani muscles all appear to be associated with SUI. Meta-analyses showed that observed bladder neck dilation and lower functional urethral length, bladder neck support and maximum urethral closure pressures are strong characteristic signs of SUI. Conclusion The pathology of SUI is multifactorial, with strong evidence pointing to bladder neck and urethral incompetence. While there is also evidence of impaired urethral support and levator ani function, standardized approaches to measurement are needed to generate higher levels of evidence.

The term 'neurogenic bladder' describes lower urinary tract dysfunction that has occurred likely as a result of a neurological injury or disease (1) . The International Continence Society (ICS) defines 'neurogenic lower urinary tract dysfunction' (NLUTD) as 'lower urinary tract dysfunction due to disturbance of the neurologic control mechanism.' This broad definition is used to describe a multitude of conditions of varying severity.Common causes of NLUTD include: spinal cord injury (SCI), multiple sclerosis (MS) and myelomeningocele (MMC). Other causes of NLUTD include: Parkinson's disease, cerebrovascular accidents, traumatic brain injury, brain or spinal cord tumor, cauda equina syndrome, transverse myelitis, multisystem atrophy, pelvic nerve injury and diabetes.It is well described that neurological disorders can lead to urologic complications including: urinary incontinence, UTIs, urolithiasis, sepsis, ureteric obstruction, vesicoureteric reflux (VUR) and renal failure (2) . Due to the potential morbidity, and even mortality, initial investigation, ongoing management and surveillance is warranted in this patient population. Despite the frequency and potential severity of NLUTD, there are few high-quality studies in the literature to guide urological practices. CUAJ -CUA Guideline Kavanagh et al Guideline: Neurogenic bladderPrior neurogenic guidelines vary in their clinical assessment, investigations utilized and surveillance strategies (2)(3)(4)(5)(6) . The primary reason is that there is limited evidence to support a common strategy. The purpose of this guideline is to help urologists to identify high-risk patients with NLUTD and to provide an approach to the management and surveillance of patients with NLUTD. ClassificationThe etiology of a NLUTD is often classified based on whether the primary lesion is suprapontine, suprasacral, sacral or infrasacral (7) . A complementary system was developed by Madersbacher et al. based on the function of the detrusor muscle and of the external sphincter (8) . These systems allow a physician to have a general idea of how the lower urinary tract is likely to behave in SCI patients with more complete injuries. (Figure 1). Newer systems using MR urography in combination with urodynamics (UDS) have also been proposed. (9) MethodologyThis review was performed according to the methodology recommended by the Canadian Urologic Association (10) . EmBASE and Medline databases were used to identify literature relevant to the early urological care of NLUTD patients. Recommendations were developed by consensus and graded using a modified Oxford system which identifies level of evidence (LOE) and grade of recommendation (GOR). This complete version includes the full text of the guidelines (including the sections in the executive summary). Canadian epidemiology of neurogenic bladderThere are 3.7 million Canadians living with a neurologic condition, (11,12) three common types of neurologic conditions are Multiple Sclerosis (MS), Spina Bifida (SB) and Spinal Cord Injury (SCI). In ...

The urinary tract exits to a body surface area that is densely populated by a wide range of microbes. Yet, under most normal circumstances, it is typically considered sterile, i.e., devoid of microbes, a stark contrast to the gastrointestinal and upper respiratory tracts where many commensal and pathogenic microbes call home. Not surprisingly, infection of the urinary tract over a healthy person’s lifetime is relatively infrequent, occurring once or twice or not at all for most people. For those who do experience an initial infection, the great majority (70% to 80%) thankfully do not go on to suffer from multiple episodes. This is a far cry from the upper respiratory tract infections, which can afflict an otherwise healthy individual countless times. The fact that urinary tract infections are hard to elicit in experimental animals except with inoculum 3–5 orders of magnitude greater than the colony counts that define an acute urinary infection in humans (105 cfu/ml), also speaks to the robustness of the urinary tract defense. How can the urinary tract be so effective in fending off harmful microbes despite its orifice in a close vicinity to that of the microbe-laden gastrointestinal tract? While a complete picture is still evolving, the general consensus is that the anatomical and physiological integrity of the urinary tract is of paramount importance in maintaining a healthy urinary tract. When this integrity is breached, however, the urinary tract can be at a heightened risk or even recurrent episodes of microbial infections. In fact, recurrent urinary tract infections are a significant cause of morbidity and time lost from work and a major challenge to manage clinically. Additionally, infections of the upper urinary tract often require hospitalization and prolonged antibiotic therapy. In this chapter, we provide an overview of the basic anatomy and physiology of the urinary tract with an emphasis on their specific roles in host defense. We also highlight the important structural and functional abnormalities that predispose the urinary tract to microbial infections.

Among patients with SCI or MS, we demonstrated non-significant trends towards improvement in some urodynamic parameters with mirabegron 50 mg compared to placebo, and a significantly lower neurogenic bladder symptom burden.

Introduction-Surgical therapies for prostate cancer and other pelvic malignancies often result in neuronal damage and debilitating loss of sexual function due to cavernous nerve trauma. Advances in the neurobiology of growth factors have heightened clinical interest for the development of protective and regenerative neuromodulatory strategies targeting cavernous nerve recovery following injury.

BackgroundDuring normal development in human and other placental mammals, the embryonic cloacal cavity separates along the axial longitudinal plane to give rise to the urethral system, ventrally, and the rectum, dorsally. Defects in cloacal development are very common and present clinically as a rectourethral fistula in about 1 in 5,000 live human births. Yet, the cellular mechanisms of cloacal septation remain poorly understood.Methodology/Principal FindingsWe previously detected Bone morphogenetic protein 7 (Bmp7) expression in the urorectal mesenchyme (URM), and have shown that loss of Bmp7 function results in the arrest of cloacal septation. Here, we present evidence that cloacal partitioning is driven by Bmp7 signaling in the cloacal endoderm. We performed TUNEL and immunofluorescent analysis on cloacal sections from Bmp7 null and control littermate embryos. We found that loss of Bmp7 results in a dramatic decrease in the endoderm survival and a delay in differentiation. We used immunological methods to show that Bmp7 functions by activating the c-Jun N-terminal kinase (JNK) pathway. We carried out confocal and 3D imaging analysis of mitotic chromosome bundles to show that during normal septation cells in the cloacal endoderm divide predominantly in the apical-basal direction. Loss of Bmp7/JNK signaling results in randomization of mitotic angles in the cloacal endoderm. We also conducted immunohistochemical analysis of human fetal sections to show that BMP/phospho-SMAD and JNK pathways function in the human cloacal region similar as in the mouse.Conclusion/SignificanceOur results strongly indicate that Bmp7/JNK signaling regulates remodeling of the cloacal endoderm resulting in a topological separation of the urinary and digestive systems. Our study points to the importance of Bmp and JNK signaling in cloacal development and rectourethral malformations.