Detrusor-Overactivity-Related Voiding in Women Mimics Bladder Outflow Obstruction and Conceals Underactivity.

OBJECTIVE: Urodynamics of the storage phase showing detrusor overactivity is com- mon in neurogenic bladder patients. Terminal detrusor overactivity, which is defined by involuntary detrusor contraction that cannot be inhibited, causes urinary incon- tinence. Such incontinence causes a unique voiding in neurogenic bladder patients. During the voiding phase, the detrusor pressure at Qmax (Pdet.Qmax)/maximum flow rate (Qmax) (P/Q) is the gold standard for differentiating between detrusor underactiv- ity and bladder outflow obstruction. We investigated whether a valid identification of lower urinary tract dysfunction could be established from P/Q assessment of detrusor overactivity-related voiding patients. METHODS: This study evaluated 2 types of voiding. Detrusor overactivity-related void- ing is involuntary detrusor contraction that results in micturition or voiding after per- mission to void when detrusor overactivity has occurred, while voluntary voiding is voiding voluntarily after permission to void and without terminal detrusor overactivity. We evaluated female patients with neurogenic bladder who could undergo micturition without catheterization. A pressure flow study compared the 2 groups. RESULTS: Comparison of the detrusor overactivity-related voiding group (n=20) and the voluntary voiding group (n=12) found statistically significant differences with a lower Qmax and higher Pdet.Qmax (P=.01) in the detrusor overactivity-related void- ing group. The linear regression analysis P/Q plot showed the positivity and negativity value of the slope that was reversed in the 2 groups (-0.089 vs. 0.198). CONCLUSION: Current results showed different P/Q plot patterns between 2 types of voiding in patients with neurogenic bladder. These findings suggest there is increased detrusor pressure observed in detrusor overactivity-related voiding that mimics out- flow obstruction.

Episodes of Febrile Urinary Tract Infections Occur More Often in the Winter in Patients with Spina Bifida.

OBJECTIVE: Febrile urinary tract infections, which commonly occur in spina bifida patients, can cause renal dysfunction. To help prevent febrile urinary tract infection occurrence, a better understanding of any seasonal tendencies would be beneficial. MATERIALS AND METHODS: Study points evaluated included: (i) with or without febrile urinary tract infections, (ii) type of urinary management in patients with febrile urinary tract infections, (iii) number of febrile urinary tract infection occurrences, and (iv) season associated with episode. Febrile urinary tract infection was defined by medical records specifically ascribing the term and clinical presentations consistent with the diagnosis. We evaluated febrile urinary tract infection incidence per 1 person, risk odds, expected values, and chi-square analysis. RESULTS: This study examined 140 patients (79 males, 61 females). The patient's age at the first visit ranged from 2 days to 43.7 years old (median: 3.0 years old). The observation period was 0.6-43.7 years (median: 11.5 years). (i) Febrile urinary tract infection occurred in 68 cases, (ii) urinary management included: full clean intermittent catheterization: 49 cases, autoaugmented bladder: 15 cases, self-voiding: 8 cases, clean intermittent catheterization + indwelling catheter at night time: 5 cases, self-voiding + clean intermittent catheterization: 4 cases, vesicocutaneostomy: 2 cases, (iii) number of febrile urinary tract infection episodes: 2 times or less: 40 cases, 3-5 times: 20 cases, over 6 times: 8 cases, and (iv) total number of febrile urinary tract infection episodes was 183, with spring: 41, summer: 44, autumn: 37, and winter: 61. Risk odds of the incidence (one season vs. the other season) were spring: 0.870 (P = .425), summer: 0.954 (P = .784), autumn: 0.755 (P = .120), and winter 1.497 (P = .009).

Urodynamic evaluation of the efficacy of vibegron, a new ß3-adrenergic receptor agonist, on lower urinary tract function in children and adolescents with overactive bladder.

INTRODUCTION: Idiopathic overactive bladder (OAB) is defined as an urgency symptom with or without urge incontinence, which is not due to known neurological abnormalities. Since children present with variable symptoms, pediatric nonneurogenic idiopathic OAB is a condition that is difficult to diagnose and treat. Although there are few reports on bladder function in pediatric patients compared to adult patients, it can be useful for diagnosis. Antimuscarinic therapy is the pharmacological mainstay of OAB management. However, antimuscarinic use is limited by side effects and Insufficient effects. Vibegron, a new drug with a different mechanism of action (ß3-adrenoreceptor agonist), was recently introduced for treating OAB in adults but has not been studied in the pediatric population. OBJECTIVE: This study aimed to determine the efficacy and tolerability of vibegron in children and adolescents with idiopathic OAB. STUDY DESIGN: We conducted a retrospective study enrolling pediatric patients with OAB whose symptoms did not improve with behavioral therapy or pharmaceutical therapy. Efficacy and tolerability were assessed via a question, and patients underwent video-urodynamic testing before and during treatment with once-daily 50 mg vibegron. Statistical differences were evaluated using Wilcoxon matched-pairs signed-rank tests. RESULTS: Out of the 17 patients that were recruited, full study with two urodynamic studies were confirmed by 11 patients. OAB symptoms improved in 14 (82.4%) patients, and 3 patients discontinued treatment because of ineffectiveness. No patients discontinued treatment because of intolerance to vibegron. The median (IQR) first desire to void (133 [82-185]-161 [123-227] mL), bladder capacity (158 [136-238]-204 [150-257] mL), and bladder compliance (18.1 [9.1-76.7]-34.0 [30.0-82.3] mL/cm H2O) improved significantly post treatment compared to before treatment. Detrusor overactivity disappeared in one of the eight patients with this condition. The parameters of voiding function did not change significantly after the administration of vibegron. DISCUSSION: Treatment with vibegron significantly improved clinical and urodynamic parameters of pediatric OAB with no adverse effects. Little information is available regarding the feasibility of switching drugs when patients discontinue prior pharmacological therapy because of insufficient efficacy or poor tolerability in children. Vibegron may be a promising OAB treatment option with a better balance of efficacy and tolerability. CONCLUSIONS: Vibegron is an alternative agent for pediatric patients with idiopathic OAB for improving both subjective symptoms and lower urinary tract function. Future prospective randomized studies with larger sample sizes must be conducted to validate the results of the present study.

Ymer acts as a multifunctional regulator in nuclear factor-κB and Fas signaling pathways.

The nuclear factor (NF)-κB family of transcription factors regulates diverse cellular functions, including inflammation, oncogenesis and apoptosis. It was reported that A20 plays a critical role in the termination of NF-κB signaling after activation. Previously, we showed that Ymer interacts and collaborates with A20, followed by degradation of receptor-interacting protein (RIP) and attenuation of NF-κB signaling. Here we show the function of Ymer in regulation of several signaling pathways including NF-κB on the basis of results obtained by using Ymer transgenic (Ymer Tg) mice. Ymer Tg mice exhibited impaired immune responses, including NF-κB and mitogen-activated protein kinase (MAPK) activation, cell proliferation and cytokine production, to tumor necrosis factor (TNF)-α, polyI:C or lipopolysaccharide (LPS) stimulation. Ymer Tg mice were more resistant to LPS-induced septic shock than wild-type mice. Transgene of Ymer inhibited the onset of glomerulonephritis in lpr/lpr mice as an autoimmune disease model. In contrast to the inflammatory immune response to LPS, Fas-mediated cell death was strongly induced in liver cells of Ymer Tg mice in which Ymer is abundantly expressed. These findings suggest that Ymer acts as a regulator downstream of several receptors and that Ymer functions as a positive or negative regulator in a signaling pathway-dependent manner.