A highly polarized TH2 bladder response to infection promotes epithelial repair at the expense of preventing new infections.

Urinary tract infections (UTIs) typically evoke prompt and vigorous innate bladder immune responses, including extensive exfoliation of the epithelium. To explain the basis for the extraordinarily high recurrence rates of UTIs, we examined adaptive immune responses in mouse bladders. We found that, following each bladder infection, a highly T helper type 2 (TH2)-skewed immune response directed at bladder re-epithelialization is observed, with limited capacity to clear infection. This response is initiated by a distinct subset of CD301b+OX40L+ dendritic cells, which migrate into the bladder epithelium after infection before trafficking to lymph nodes to preferentially activate TH2 cells. The bladder epithelial repair response is cumulative and aberrant as, after multiple infections, the epithelium was markedly thickened and bladder capacity was reduced relative to controls. Thus, recurrence of UTIs and associated bladder dysfunction are the outcome of the preferential focus of the adaptive immune response on epithelial repair at the expense of bacterial clearance.

Sexual Function and Dysfunction in Individuals with Spina Bifida: A Systematic Review.

OBJECTIVE: To conduct a systematic review of self-reported experiences of sexual function and dysfunction in individuals with spina bifida (SB). MATERIALS AND METHODS: Medline, Embase, and Web of Science were systematically searched. Studies included contained self-reported data from SB patients on one or more of the following sexual function domains: Genital sensitivity, orgasm, erectile function, ejaculation, lubrication, and/or dyspareunia. Two authors independently assessed eligibility, extracted data, and cross-checked results, with disagreements resolved by consensus. Studies included contained self-reported data from SB patients on one or more of the following sexual function domains: Genital sensitivity, orgasm, erectile function, ejaculation, lubrication, and/or dyspareunia. RESULTS: Systematic search yielded 23 studies representing 1441 patients (816 males, 625 females). Eight utilized questionnaires validated in non-SB adults; the remainder used semi-structured interviews and non-validated instruments. Eleven assessed dysfunctions in both sexes, 10 in males, and 2 in females. Erectile function and orgasm were the most commonly assessed outcomes in males and females respectively. 12%-88% of males experienced erectile dysfunction; a majority (51%-90%) reported normal ejaculatory function. Many females were unable to experience orgasm (28%-63%). CONCLUSION: Males with SB report significant erectile and ejaculatory dysfunction. Both sexes report impaired orgasms and genital sensitivity. SB-specific instruments assessing sexual dysfunction are needed in order to improve multidisciplinary care for this population.

Pediatric Neurogenic Bladder and Bowel Dysfunction: Will My Child Ever Be out of Diapers?

CONTEXT: Managing patient and parent expectations regarding urinary and fecal continence is important with congenital conditions that produce neurogenic bladder and bowel dysfunction. Physicians need to be aware of common treatment algorithms and expected outcomes to best counsel these families. OBJECTIVE: To systematically evaluate evidence regarding the utilization and success of various modalities in achieving continence, as well as related outcomes, in children with neurogenic bladder and bowel dysfunction. EVIDENCE ACQUISITION: We performed a systematic review of the literature in PubMed/Medline in August 2019. A total of 114 publications were included in the analysis, including 49 for bladder management and 65 for bowel management. EVIDENCE SYNTHESIS: Children with neurogenic bladder conditions achieved urinary continence 50% of the time, including 44% of children treated with nonsurgical methods and 64% with surgical interventions. Patients with neurogenic bowel problems achieved fecal continence 75% of the time, including 78% of patients treated with nonsurgical methods and 73% with surgical treatment. Surgical complications and need for revisions were high in both categories. CONCLUSIONS: Approximately half of children with neurogenic bladder dysfunction will achieve urinary continence and about three-quarters of children with neurogenic bowel dysfunction will become fecally continent. Surgical intervention can be successful in patients refractory to nonsurgical management, but the high complication and revision rates support their use as second-line therapy. This is consistent with guidelines issued by the International Children's Continence Society. PATIENT SUMMARY: Approximately half of children with neurogenic bladder dysfunction will achieve urinary continence, and about three-quarters of children with neurogenic bowel dysfunction will become fecally continent. Most children can be managed without surgery. Patients who do not achieve continence with nonsurgical methods frequently have success with operative procedures, but complications and requirements for additional procedures must be expected.

The potential repertoire of the innate immune system in the bladder: expression of pattern recognition receptors in the rat bladder and a rat urothelial cell line (MYP3 cells).

PURPOSE: The urothelium is a frontline sensor of the lower urinary tract, sampling the bladder lumen and stimulating an immune response to infectious and noxious agents. Pattern recognition receptors (PRRs) recognize such agents and coordinate the innate response, often by forming inflammasomes that activate caspase-1 and the release of interleukin-1. We have shown the presence of one PRR (NLRP3) in the urothelia and its central role in the inflammatory response to cyclophosphamide. The purpose of this study was to (1) assess the likely range of the PPR response by assessing the repertoire present in the rat bladder and (2) determine the utility of the MYP3 rat urothelia cell line for in vitro studies by assessing its PPR repertoire and functional responsiveness. METHODS: Immunohistochemistry was performed for seven PPRs (NLRP1, NLRP3, NLRP6, NLRP7, NLRP12, NLRC4 and AIM2) on bladder sections and MYP3 cells. For functionality, MYP3 cells were challenged with the quintessential NLRP3 activator ATP and assessed for caspase-1 activation. RESULTS: All PPRs examined were expressed in the bladder and localized to the urothelial layer with several also in the detrusor (none in the interstitia). MYP3 cells also expressed all PRRs with a variable intracellular location. ATP-stimulated caspase-1 activity in MYP3 cells in a dose-dependent manner was reduced by knockdown of NLRP3 expression. CONCLUSION: The results suggest that the bladder possesses the capacity to initiate an innate immune response to a wide array of uropathological agents and the MYP3 cells will provide an excellent investigational tool for this field.