Mechanosensitive Piezo1 channels promote neurogenic bladder fibrosis via regulating TGF-ß1/smad and Hippo/YAP1 pathways.

Bladder fibrosis is the final common pathway of neurogenic bladder (NB), and its underlying mechanisms are not fully understood. The current study aims to evaluate the involvement of Piezo1, a mechanosensitive channel, in bladder fibrosis. A full-thickness bladder specimen was taken during ileocystoplasty or ureteral reimplantation from the surgical cut's edge. By chopping off the bilateral lumbar 6 (L6) and sacral 1 (S1) spinal nerves, NB rat models were produced. Utilizing both pharmacological inhibition and Piezo1 deletion, the function of Piezo1 in the TGF-ß1-induced fibrosis model of SV-HUC-1 cells was delineated. RNA-seq, immunofluorescence, immunohistochemistry (IHC), and Western blotting were used to evaluate the degrees of fibrosis and biochemical signaling pathways. Piezo1 protein expression was noticeably elevated in the human NB bladder. The abundance of Piezo1 protein in bladder of NB rats was significantly increased. RNA-seq analysis revealed that the ECM-receptor interaction signaling pathway and collagen-containing ECM were increased in spinal cord injury (SCI)-induced bladder fibrosis. Moreover, the bladder of the NB rat model showed activation of YAP1 and TGF-ß1/Smad. In SV-HUC-1 cells, siRNA suppression of Piezo1 led to profibrotic responses and activation of the TGF-ß1/Smad pathway. However, Yoda1, a Piezo1-specific agonist, significantly reduced these effects. TGF-ß1 increased Piezo1 activation and profibrotic responses in SV-HUC-1 cells. In the TGF-ß1-induced fibrosis model of SV-HUC-1 cells, the TGF-ß1/Smad pathway was activated, whereas the Hippo/YAP1 signal pathway was blocked. Inhibition of Piezo1 further prevented this process. Piezo1 is involved in the progression of NB bladder fibrosis and profibrotic alterations in SV-HUC-1 cells, likely through regulating the TGF-ß1/Smad and Hippo/YAP1 pathways.

Inhibition of the NF-κB Signaling Pathway Alleviates Pyroptosis in Bladder Epithelial Cells and Neurogenic Bladder Fibrosis.

Most children with a neurogenic bladder (NB) have bladder fibrosis, which causes irreversible bladder dysfunction and damage to the upper urinary tract. However, the mechanism of bladder fibrosis remains unclear. This study aimed to investigate the underlying causes of bladder fibrosis. Here, the lumbar 6 (L6) and sacral 1 (S1) spinal nerves of Sprague Dawley rats were severed bilaterally to establish NB models. Using RNA-seq, we discovered that the NF-κB signaling pathway and inflammation were upregulated in spinal cord injury (SCI)-induced bladder fibrosis. Subsequent Western blotting, enzyme-linked immunosorbent assays, immunohistochemical staining, and immunofluorescence staining verified the RNA-seq findings. To further clarify whether the NF-κB signaling pathway and pyroptosis were involved in bladder fibrosis, a TGF-ß1-treated urinary epithelial cell line (SV-HUC-1 cells) was used as an in vitro model. Based on the results of RNA-seq, we consistently found that the NF-κB signaling pathway and pyroptosis might play important roles in TGF-ß1-treated cells. Further experiments also confirmed the RNA-seq findings in vitro. Moreover, using the NLRP3 inhibitor MCC950 rescued TGF-ß1-induced fibrosis, and the NF-κB signaling pathway inhibitor BAY 11-7082 effectively rescued TGF-ß1-induced pyroptosis and the deposition of extracellular matrix by SV-HUC-1 cells. In summary, our research demonstrated for the first time that the NF-κB signaling pathway inhibition rescued bladder epithelial cells pyroptosis and fibrosis in neurogenic bladders.

The TGF-ß1 pathway is early involved in neurogenic bladder fibrosis of juvenile rats.

BACKGROUND: This study investigated whole neurogenic bladder's progression changes, as well as the expression of TGF-ß1 fibrosis pathway-related proteins in bilateral spinal nerve-amputated juvenile rats. METHODS: Sixty-four 8-week-old rats (32 bilateral L6 + S1 spinal nerve amputated and 32 sham operated) were selected. Cystometry was performed. General assessments, Masson, Sirius red, immunohistochemical staining, and western blotting of fibrosis and TGF-ß1 pathway-related proteins were conducted using bladder tissues. RESULTS: Cystometry results showed that the basal intravesical pressures and bladder capacities in nerve-amputated rats were significantly higher than those in sham-operated ones. Compared to the sham-operated groups, the bladder size and wall thickness in the nerve-amputated groups increased initially but then decreased over time. However, bladder weight continuously increased over time. Disintegration, thickening, and hypertrophy of the bladder wall were found over time in the amputated rats. Moreover, there was a significant increase in collagen III, and the ratio of collagen III/I was higher in amputated rats (P < 0.01). Finally, the expression of TGF-ß1, TGF-ßRI, Smad2, and collagen III and I increased in amputated bladder tissues, while Smad6 decreased over time. CONCLUSIONS: The main clinical features of pediatric neurogenic bladder (PNB) were detrusor paralysis and continuous intravesical pressure. Biological molecular findings are earlier than the pathophysiological findings. Therefore, early preventing bladder fibrosis by targeting TGF-ß1/Smad pathway-related proteins once knowing the PNB diagnosis might be an alternative treatment for PNB. IMPACT: The study found that the main clinical features of PNB were detrusor paralysis, continuous intravesical pressure, and increased TGF-beta/Smad signal proteins over time. The study makes contributions to the literature because it suggests biological molecular findings are earlier than the pathophysiological findings by various staining in PNB. The study investigated whole neurogenic bladder's progression changes, as well as the expression of TGF-ß1 fibrosis pathway-related proteins in the spinal nerve-injured PNB juvenile rat models, which suggests that early prevention of bladder fibrosis by targeting TGF-ß1/Smad pathway-related proteins once knowing the PNB diagnosis might be an alternative treatment for pediatric neurogenic bladder.

Urological malignancies in neurogenic patients.

PURPOSE OF REVIEW: To review recent literature related to urologic malignancies in patients with neurogenic lower urinary tract dysfunction (NLUTD). We performed a literature search of electronic databases (PubMed, ScienceDirect, Scopus, and CIANHL), with a focus on articles published between January 2015 and December 2019. RECENT FINDINGS: Recent reports demonstrate a lower incidence of bladder cancer in the NLUTD population than previously found, although still significantly higher than the general population. Bladder cancer in patients with NLUTD is usually diagnosed at a younger age, and is associated with higher rates of squamous cell cancer, a higher stage at presentation, and increased mortality. Evidence for screening for bladder cancer in NLUTD is conflicting, with no formal protocols proven for general use. NLUTD has been shown to have a lower rate of prostate cancer, and may be associated with an earlier diagnosis of renal cancer. SUMMARY: Genitourinary malignancies, although still rare, are an important source of morbidity and mortality in patients with NLUTD. Physicians should recognize that bladder cancer in NLUTD is often a lethal disease. Further research is needed to assist physicians with early recognition of these malignancies to improve patient outcomes.

Treatment of neurogenic lower urinary tract symptoms: main contributions from 2018 and 2019.

PURPOSE OF REVIEW: This review aims to update the studies involving the treatment of lower urinary tract symptoms (LUTS) in neurogenic patients, published in the last two years. RECENT FINDINGS: Treatment of neurogenic LUTS (NLUTS) patients with ß3 adrenoreceptor agonists was investigated in real-life conditions. A randomized controlled trial compared the efficacy of antimuscarinics versus onabotulinum toxin A in neurogenic patients. The use of desmopressin to treat nocturia in multiple sclerosis patients is also reported. The long-term treatment with BontA efficacy, its discontinuation, and possible strategies to maintain patients on treatment were also evaluated. Sacral neuromodulation and tibial nerve stimulation are continuously being evaluated in neurogenic patients, especially in the last years. SUMMARY: The management of urinary tract infections and vesical lithiasis, two common complications in NLUTS patients, and the management of both these patients was assessed in clinical trials.A trial evaluating the use of the anti-Nogo-A antibody after a spinal cord injury to facilitate neuronal rewiring and prevent or improve NLUTS was reported for the first time.

A Case of Sulfhemoglobinemia Secondary to a Urinary Tract Infection.

Sulfhemoglobinemia (SulfHb) is a rare dyshemoglobinemia that can present with cyanosis in the absence of respiratory distress. It has been reported secondary to drug ingestion and chronic constipation. We present a case of SulfHb in an adolescent female with spina bifida and neurogenic bladder in the setting of an Escherichia coli urinary tract infection. An arterial blood gas differentiated a dyshemoglobinemia from other causes of hypoxemia. The resolution was achieved with antibiotics and red cell transfusion. Here we review the pathophysiology of SulfHb and contribute a unique case report to the limited body of literature on this topic.

Electroacupuncture improves neurogenic bladder dysfunction through activation of NGF/TrkA signaling in a rat model.

OBJECTIVE: To observe the effect of electroacupuncture on the morphological change of the bladder tissue and the protein expression levels of NGF, TrkA, p-TrkA, AKT, and p-AKT in the bladder tissue of rats with neurogenic bladder after suprasacral spinal cord injury and to preliminarily explore its partial mechanism of action. METHODS: Eighty female Sprague-Dawley rats were randomly divided into blank group, model group, electroacupuncture group, model/siNGF group, and electroacupuncture/siNGF group according to random number table method with 16 rats in each group. Eighty Neurogenic bladder models after suprasacral spinal cord injury were established by adopting a modified spinal cord transection method. Electroacupuncture intervention was conducted on the 19th day after modeling. The bladder function was detected by bladder weight, urine output, serum BUN, and urine protein. After treatment for 7 consecutive days, the rats were killed and the bladder tissues were removed rapidly for microscopic observation of morphological change after hematoxylin and eosin stain and for determination of the protein expression levels of NGF, TrkA, p-TrkA, AKT, and p-AKT via Western blot analysis. The transcription of NGF was measured by reverse-transcription polymerase chain reaction. RESULTS: After treatment, compared with the blank group, the bladder weight of model and electroacupuncture groups were significantly increased (P < 0.05). Compared with the model group, the bladder weight of the electroacupuncture group was decreased (P > 0.05). Compared with the blank group, the urine output of the model group was increased ( P < 0.05). Compared with the blank group, the urine output of the electroacupuncture group was increased ( P > 0.05). Compared with the blank group, the serum BUN of the model group was increased ( P < 0.05). Compared with the blank group, the serum BUN of the electroacupuncture group was increased ( P > 0.05). Compared with the blank group, the urine protein of the model group was increased ( P < 0.05). Compared with the blank group, the urine protein of the electroacupuncture group was increased ( P > 0.05). The expression of NGF, p-TrkA, and p-AKT in the model and electroacupuncture groups was obviously higher than that in the blank group ( P < 0.05). The expression of NGF, p-TrkA, and p-AKT in the electroacupuncture group was higher than that in the model group. The expression of TrkA and AKT were unchanged in blank, model, and electroacupuncture groups ( P > 0.05). After tail vein injection with siNGF lentivirus, the expression of NGF in the model/siNGF group and electroacupuncture/siNGF group was significantly decreased ( P < 0.05). And the protein level of p-AKT and p-TrkA was significantly lower than that of the model and electroacupuncture groups ( P < 0.05). CONCLUSION: Sacral electroacupuncture therapy can improve the expression of both NGF/TrkA signaling and AKT signaling in the local nerve of the damaged spinal cord, inhibit apoptosis of the damaged spinal cord, protect nerve cells, and promote the recovery of the damaged nerve. At the same time, electroacupuncture can promote the coordination of micturition reflex and improve neurogenic bladder function after the spinal cord injury.

Prevalence, management, and prognosis of bladder cancer in patients with neurogenic bladder: A systematic review.

AIM: To perform a systematic review of the literature regarding epidemiology, diagnosis, management and prognosis of bladder cancer in the neuro-urological patient population, in order to serve as a basis for future recommendations and research. METHODS: A systematic review was performed according to the PRISMA-Preferred Reporting Items for Systematic Reviews and Meta-Analyzes Statement. Embase was searched for studies providing data on epidemiology, diagnosis, management and prognosis of bladder cancer in neuro-urological patients. RESULTS: After screening 637 abstracts, 15 studies (13 retrospective and 2 prospective studies) were included in this study. We identified 332 patients (0.3%) who were diagnosed with bladder cancer. This mostly affected mostly men (59.3%) and spinal cord injured patients (98.8%). Mean age at diagnosis was 56.1 years. Bladder cancer occurred after a long period of evolution of the neurological disease (24.9 years). Gross hematuria was the predominating presenting symptom (31.6% of cases). Indwelling urethral or supra-pubic catheters were used in 44.5% of patients. The most frequent histological subtype of bladder cancer was transitional cell carcinoma (53.1%), followed by squamous cell carcinoma (33.5%). Muscle-invasive bladder cancer was reported in 67.7% of patients. The mean cancer-specific mortality rate was of 47.1%. CONCLUSIONS: The prevalence and high mortality rate of bladder cancer in neuro-urological patients underlines the importance of long-term follow-up in this specific population. This highlights the necessity of further studies in this field.

Characterization of voiding function and structural bladder changes in a rat model of neurogenic underactive bladder disease.

OBJECTIVES: To create an animal model for neurogenic underactive bladder disease (UAB) and identify markers to describe secondary myogenic changes in the bladder wall. MATERIALS AND METHODS: Male rats underwent either bilateral pelvic nerve injury or sham surgery. Four weeks after surgery functional evaluation was performed and tissue was harvested. Functional evaluation consisted of analysis of voiding pattern, 24-h urine collection in a metabolic cage, in vivo cystometry and in-vitro contractile function assessment. PCR and immunohistochemical localization of different smooth muscle cell and extracellular matrix markers was performed on bladder strips. RESULTS: After pelvic nerve injury, dry bladder weight increased and voiding contractions were absent, resulting in overflow incontinence. In-vitro contractile response to carbachol was decreased. This was paired with an upregulation of synthetic smooth muscle cell (SMC) markers mRNA expression such as retinol binding protein 1 (RBP1), myosin 10 (MYH10) and osteopontin (OPN), and a downregulation of contractile SMC marker smoothelin (SMTL). The SMTL/OPN mRNA ratio was 50 times higher in sham bladders compared to PNI bladders. CONCLUSIONS: The loss of in-vivo and in-vitro contractile function following pelvic nerve transection is characterized by a switch from a contractile to synthetic SMC phenotype, which is best characterized by the ratio SMTL/OPN mRNA expression. Modulating this phenotypical switch is a potential target for the development of UAB therapy. We suggest for the first time a set of markers that may be useful to evaluate therapeutic strategies on improvements in bladder wall structure.

Analysis of bladder cancer subtypes in neurogenic bladder tumors.

INTRODUCTION: To establish if the validated tumor biomarkers of luminal and basal bladder cancers in non neuro-urological patients are applicable to a neuro-urological population. MATERIALS AND METHODS: We retrieved bladder cancer samples from neuro-urological patients (n = 20) and non-neurological controls (n = 40). The expression of GATA3 and CK5/6 was analyzed using immunohistochemistry of microarray tissue sections. We also assessed the correlation between previous biomarker expression, gender, age, tumor stage (non-muscle-invasive bladder cancer (NMIBC)/muscle-invasive bladder cancer (MIBC)), squamous-cell differentiation and basal/luminal subtypes using Pearson's correlation coefficient (r). RESULTS: Mean age at diagnosis of bladder cancer in neuro-urological patients was 53.2 years (min 41-max 73). MIBC was found in 13 neuro-urological patients (65%). The luminal subtype was identified in 7 samples (35%, all urothelial differentiation). The basal subtype was found in 13 samples (65%): 12 squamous-cell and 1 sarcomatoid differentiation. GATA3 and CK5/6 were expressed in 6 (30%) neuro-urological patients. A significant positive correlation was found between GATA3 expression and the luminal subtype (p = 0.00001, r = 0.5676). This was not the case with the neuro-urological status (r = -0.307). A poor correlation was found between CK5/6 expression and the neuro-urological status (r = 0.471 and -0.471), squamous-cell differentiation (r = 0.092), tumor stage NMIBC/MIBC (r = -0.118 and 0.118) and basal/luminal subtypes (r = -0.157 and 0.194). CONCLUSION: In summary, the expression of GATA3 and CK5/6 could not differentiate the different subtypes of bladder cancer in neuro-urological patients. This implies that their specific histopathological signature is distinct from non neuro-urological patients. Additional pathways may be involved to explain their urothelial carcinogenesis mechanism.

Expression of autophagy in different stages of neurogenic bladder after spinal cord injury in rats.

STUDY DESIGN: Experimental study. OBJECTIVES: To investigate the expression of autophagy in different stages of the neurogenic bladder after spinal cord injury (SCI) in rats. SETTING: Second Hospital of Shandong University, Jinan, China. METHODS: A total of 36 Wistar rats were divided into the SCI and control groups. In total, six animals were killed and sampled from each group at 1, 4 and 14 days after surgery of T10-T11 level. BBB scale, residual urine volume and urinary bladder function score were estimated at each time point. The expression of microtubule-associated protein 1 light chain 3 (LC3) and P62 was detected using western blot analysis, immunofluorescence staining or real-time PCR (RT-PCR). RESULTS: The locomotor functions of the hindlimbs and the bladder function of the SCI group rats were lost after surgery, but gradually recovered from 1 day. Western blot showed that the LC3-II/actin was higher in the SCI than in the control group. Immunofluorescence staining revealed that LC3 and P62 were expressed in bladder smooth muscle cell. RT-PCR showed a remarkably increased LC3 mRNA expression at 1, 4 and 14 days in the SCI than in the control group. The P62 mRNA level of the SCI bladder tissues did not differ from that of the control group at 1 day but decreased at 4 and 14 days after surgery. CONCLUSIONS: Autophagy is activated during the recovery of the bladder after SCI and sustained. Autophagy may play an important role in bladder neurogenesis and may represent one of the mechanisms of bladder self-repair.

Effect of type II diabetes on male rat bladder contractility.

Type II diabetes is the most prevalent form of diabetes. One of the primary complications of diabetes that significantly affects quality of life is bladder dysfunction. Many studies on diabetic bladder dysfunction have been performed in models of type I diabetes; however, few have been performed in animal models of type II diabetes. Using the Zucker Diabetic Fatty (ZDF) rat model of type II diabetes, we examined the contractility and sensitivity of bladder smooth muscle in response to mediators of depolarization-induced contraction, muscarinic receptor-mediated contraction, ATP-induced contraction, and neurogenic contraction. Studies were performed at 16 and 27 wk of age to monitor the progression of diabetic bladder dysfunction. Voiding behavior was also quantified. The entire bladder walls of diabetic rats were hypertrophied compared with that of control rats. Contractility and sensitivity to carbachol and ATP were increased at 27 wk in bladder smooth muscle strips from diabetic rats, suggesting a compensated state of diabetic bladder dysfunction. Purinergic signaling was increased in response to exogenous ATP in bladders from diabetic animals; however, the purinergic component of neurogenic contractions was decreased. The purinergic component of neurogenic contraction was reduced by P2X receptor desensitization, but was unchanged by P2X receptor inhibition in diabetic rats. Residual and tetrodotoxin-resistant components of neurogenic contraction were increased in bladder strips from diabetic animals. Overall, our results suggest that in the male ZDF rat model, the bladder reaches the compensated stage of function by 27 wk and has increased responsiveness to ATP.

Augmentation cystoplasty: Urodynamic and metabolic outcomes at 10-year follow-up.

OBJECTIVE: To review the urodynamic outcomes, renal function and metabolic complications after augmentation cystoplasty with at least 10 years of follow-up. METHODS: Augmentation cystoplasty performed in two tertiary referral centers from 1995 to 2004 were reviewed. Ten years or more postoperative course was studied by review of the clinical notes, urodynamic reports and laboratory results. RESULTS: A total of 40 patients were included in this study. The mean age at surgery was 43 years, and 47.5% of patients were female. Median follow up was 13 years. Bladder capacity significantly increased from 283 ± 151 to 492 ± 123 mL (P < 0.01), with a percentage change of +130%. The compliance of the bladder was increased by 87%, and detrusor overactivity decreased by 54.2%. There were no significant changes in preoperative and postoperative estimated glomerular filtration rate (68.3 mL/min vs. 76.6 mL/min, P = 0.798). Three patients (7.5%) had more than one episode of symptomatic urinary tract infection per year. CONCLUSION: The present study confirms the effectiveness of augmentation cystoplasty in increasing bladder capacity, improving bladder compliance and reducing detrusor overactivity. The preservation of renal function and low metabolic complication rate provide solid evidence for carrying out this time-honored procedure in patients with neurogenic or non-neurogenic bladder dysfunction.

[Efficacy of combination therapy with mirabegron for anticholinergic-resistant neurogenic bladder: videourodynamic evaluation].

Using a videourodynamic study, we examined the efficacy of combination therapy with mirabegron for anticholinergic-resistant neurogenic bladder. We retrospectively studied 7 patients with neurogenic bladder (5 males and 2 females) who had detrusor overactivity (DO) or low compliance bladder (＜10 ml/cmH2O) despite taking anticholinergic medication. Bladder deformity was categorized from G0 to G3 by Ogawa's classification. Mean age of study patients was 51 years (25-76). Underlying diseases were spinal cord injury in 3 patients, spina bifida in 2, spinal cord infarction in 1, and post-radical hysterectomy in 1. Preceding anticholinergic medication was solifenacin 5 mg in 1 patient, solifenacin 10 mg in 5, and tolterodine 4 mg in 1. Before mirabegron, bladder deformity was G1 in 4 patients, G2 in 1 and G3 in 2, and vesicoureteral reflux (VUR) was detected in 3 patients. Five and 4 patients had detrusor overactivity and low compliance bladder, respectively. Videourodynamic study was reevaluated at a mean of 7 months (2- 12 months) after mirabegron. After mirabegron, urinary incontinence was improved in all patients. G3 bladder deformity was improved to G2 and G1 in one patient each, and VUR disappeared in all 3 patients. DO disappeared in 2 of the 5 patients, and bladder compliance was improved in all 4 patients with low compliance bladder. In conclusion, combination therapy of mirabegron is effective and beneficial for anticholinergic-resistant neurogenic bladder.

Oral mucosa stem cells alleviates spinal cord injury-induced neurogenic bladder symptoms in rats.

BACKGROUND: Spinal cord injury (SCI) deteriorates various physical functions, in particular, bladder problems occur as a result of damage to the spinal cord. Stem cell therapy for SCI has been focused as the new strategy to treat the injuries and to restore the lost functions. The oral mucosa cells are considered as the stem cells-like progenitor cells. In the present study, we investigated the effects of oral mucosa stem cells on the SCI-induced neurogenic bladder in relation with apoptotic neuronal cell death and cell proliferation. RESULTS: The contraction pressure and the contraction time in the urinary bladder were increased after induction of SCI, in contrast, transplantation of the oral mucosa stem cells decreased the contraction pressure and the contraction time in the SCI-induced rats. Induction of SCI initiated apoptosis in the spinal cord tissues, whereas treatment with the oral mucosa stem cells suppressed the SCI-induced apoptosis. Disrupted spinal cord by SCI was improved by transplantation of the oral mucosa stem cells, and new tissues were increased around the damaged tissues. In addition, transplantation of the oral mucosa stem cells suppressed SCI-induced neuronal activation in the voiding centers. CONCLUSIONS: Transplantation of oral mucosa stem cells ameliorates the SCI-induced neurogenic bladder symptoms by inhibiting apoptosis and by enhancing cell proliferation. As the results, SCI-induced neuronal activation in the neuronal voiding centers was suppressed, showing the normalization of voiding function.

New grading system for upper urinary tract dilation using magnetic resonance urography in patients with neurogenic bladder.

BACKGROUND: In patients with neurogenic bladder (NB), elevated intravesical pressures can be transmitted to the upper urinary tract, causing hydronephrosis (HN) and ureteral dilation (UD), which are referred to as upper urinary tract dilation (UUTD). Ureteral obstruction at the bladder wall is another cause for UUTD, but is less of a concern. UUTD can lead to chronic renal failure. Therefore, evaluation and protection of UUT function is extremely important in the management for NB. Currently, the most common method by which to detect HN and UD is ultrasonography (US). The Society for Fetal Urology (SFU) established an US HN grading system in 1993, but this system was found to have some defects. The purpose of this study is to describe a new grading system for UUTD, including both HN and UD, based on magnetic resonance urography (MRU) and to correlate the new grading system with the SFU grading system for HN. METHODS: A retrospective review of 70 patients with unilateral or bilateral UUTD was completed. Ninety-five sides in patients with UUTD were graded by the MRU-UUTD and SFU-HN grading systems. The results from the two grading systems were compared for each UUTD. RESULTS: The MRU-UUTD grading system revealed the following percentages for each grade: grade 0, 0; 1, 10.5%; 2, 19%; 3, 42.1%; and 4, 28.4%. The SFU-HN grading system revealed the following percentages for each grade: 0, 0; 1, 10.5%; 2, 19%; 3, 36.8%; and 4, 33.7%. There was no significant systematic difference between the two grading systems (p > 0.05), but a significant difference between grades 3 and 4 (p < 0.05). CONCLUSIONS: The MRU-UUTD grading system correlates well with SFU-HN grade, provides an objective and comprehensive evaluation for UUTD, and can be used for longitudinal monitoring of UUTD. This new grading system allows for better informed clinical decision-making, identifying changes in UUTD.

A pilot prospective study to evaluate whether the bladder morphology in cystography and/or urodynamic may help predict the response to botulinum toxin a injection in neurogenic bladder refractory to anticholinergics.

BACKGROUND: We have observed different clinical responses to botulinum toxin A (BTX-A) in patients who had similar urodynamic parameters before the procedure. Furthermore, some bladders evaluated by cystography and cystoscopy during the procedure had different characteristics that could influence the outcome of the treatment. The aim of this study was to assess whether cystography and urodynamic parameters could help predict which patients with neurogenic detrusor overactivity (NDO) refractory to anticholinergics respond better to treatment with injection of BTX-A. METHODS: In total, 34 patients with spinal cord injury were prospectively evaluated. All patients emptied their bladder by clean intermittent catheterization (CIC) and had incontinence and NDO, despite using 40 mg or more of intravesical oxybutynin and undergoing detrusor injection of BTX-A (300 IU). Pretreatment evaluation included urodynamic, and cystography. Follow-up consisted of urodynamic and ambulatory visits four months after treatment. The cystography parameters used were bladder shape, capacity and presence of diverticula. Urodynamic parameters used for assessment were maximum cystometric capacity (MCC), maximum detrusor pressure (MDP), compliance and reflex volume (RV). RESULTS: After injection of BTX-A, 70% of the patients had success, with 4 months or more of continence. Before the treatment, there were significant differences in most urodynamic parameters between those who responded successfully compared to those who did not. Patients who responded successfully had greater MCC (p = 0.019), higher RV (p = 0.041), and greater compliance (p = 0.043). There was no significant difference in the MDP (0.691). The cystography parameters were not significantly different between these groups bladder shape (p = 0.271), capacity (p > 0.720) and presence of diverticula (p > 0.999). Statistical analyses were performed using SPSS (version 20.0) and included Student's t-test for two paired samples and Fisher's exact test, with a significance threshold of 0.05. CONCLUSIONS: This study suggests that the cystography parameters evaluated cannot be used to help predict the response to injection of BTX-A in the treatment of refractory NDO. However, the urodynamic parameters were significantly different in patients who responded to the treatment, with the exception of the MDP.

Protocol for a prospective magnetic resonance imaging study on supraspinal lower urinary tract control in healthy subjects and spinal cord injury patients undergoing intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity.

BACKGROUND: The control of the lower urinary tract is a complex, multilevel process involving both the peripheral and central nervous system. Due to lesions of the neuraxis, most spinal cord injury patients suffer from neurogenic lower urinary tract dysfunction, which may jeopardise upper urinary tract function and has a negative impact on health-related quality of life. However, the alterations to the nervous system following spinal cord injury causing neurogenic lower urinary tract dysfunction and potential effects of treatments such as intradetrusor onabotulinumtoxinA injections on lower urinary tract control are poorly understood. METHODS/DESIGN: This is a prospective structural and functional magnetic resonance imaging study investigating the supraspinal lower urinary tract control in healthy subjects and spinal cord injury patients undergoing intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity.Neuroimaging data will include structural magnetic resonance imaging (T1-weighted imaging and diffusion tensor imaging) as well as functional, i.e. blood oxygen level-dependent sensitive magnetic resonance imaging using a 3 T magnetic resonance scanner. The functional magnetic resonance imaging will be performed simultaneously to three different bladder stimulation paradigms using an automated magnetic resonance compatible and synchronised pump system.All subjects will undergo two consecutive and identical magnetic resonance imaging measurements. Healthy subjects will not undergo any intervention between measurements but spinal cord injury patients will receive intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity.Parameters of the clinical assessment including bladder diary, urinalysis, medical history, neuro-urological examination, urodynamic investigation as well as standardised questionnaires regarding lower urinary tract function and quality of life will serve as co-variates in the magnetic resonance imaging analysis. DISCUSSION: This study will identify structural and functional alterations in supraspinal networks of lower urinary tract control in spinal cord injury patients with neurogenic detrusor overactivity compared to healthy controls. Post-treatment magnetic resonance imaging measurements in spinal cord injury patients will provide further insights into the mechanism of action of treatments such as intradetrusor onabotulinumtoxinA injections and the effect on supraspinal lower urinary tract control. TRIAL REGISTRATION: ClinicalTrials.gov NCT01768910.

[Evaluation of the adhesive characteristics of uropathogenic escherichia coli strains in patients with spinal cord injuries].

The adhesion characteristics of 9 clinical E.coli strains, isolated from the urine of 9 patients with spinal cord injuries in late period were evaluated. Patient age was 21 to 54 years. Neurogenic urination disordes observed in patients were the result of a spinal injury in the cervical (5 patients), thoracic (2 patients) and thoracolumbar (2 patients) spine. The duration of disease ranged from 2 to 12 years. Despite primarily a low adhesion activity of tested strains, the formation of biofilm occurs on the surfaces having both hydrophobic (polystyrene) and hydrophilic (cover glass) properties. After 24 h, according to the photometric evaluation, 7 of 9 strains had weak, 1 - medium, and 1 - high ability to form biofilms. After 48 hours, only 4 strains had low ability to form biofilms, of whom 2 had an increase ability compared to the previous period of observation. Other strains possess the medium ability to form biofilm. When quantifying the ability of bacteria to form biofilms on the surface of the cover glass, it was revealed that a large fraction of the area of the field of view was accounted for microcolonies with size 10 microm2 at 24 hours, and microcolony with size from 100 to 1000 microm2 at 48 h. There were number of significant correlations between parameters studied. After 24 h, the correlation coefficient between the optical density (OD630) and the number, OD630 and proportion of microcolonies with size 10 to 10000 microm2 varied from 0.79 to 0.9. After 48 hours, there was a direct correlation between the OD630 and the number (r = 0.73, P = 0.025), OD630 and proportion (r = 0.81, P = 0.009) of microcolonies with size 1,000 to 10,000 mkm2.