Molecular Characterization of Non-Neurogenic and Neurogenic Lower Urinary Tract Dysfunction (LUTD) in SCI-Induced and Partial Bladder Outlet Obstruction Mouse Models.

We examined bladder function following spinal cord injury (SCI) by repeated urodynamic investigation (UDI), including external urethral sphincter (EUS) electromyography (EMG) in awake restrained mice and correlated micturition parameters to gene expression and morphological changes in the bladder. A partial bladder outlet obstruction (pBOO) model was used for comparison to elucidate both the common and specific features of obstructive and neurogenic lower urinary tract dysfunction (LUTD). Thirty female C57Bl/6J mice in each group received an implanted bladder catheter with additional electrodes placed next to the EUS in the SCI group. UDI assessments were performed weekly for 7 weeks (pBOO group) or 8 weeks (SCI group), after which bladders were harvested for histological and transcriptome analysis. SCI mice developed detrusor sphincter dyssynergia (DSD) one week after injury with high-pressure oscillations and a significantly increased maximal bladder pressure Pmax and were unable to void spontaneously during the whole observation period. They showed an increased bladder-to-bodyweight ratio, bladder fibrosis, and transcriptome changes indicative of extracellular matrix remodeling and alterations of neuronal signaling and muscle contraction. In contrast, pBOO led to a significantly increased Pmax after one week, which normalized at later time points. Increased bladder-to-bodyweight ratio and pronounced gene expression changes involving immune and inflammatory pathways were observed 7 weeks after pBOO. Comparative transcriptome analysis of SCI and pBOO bladders revealed the activation of Wnt and TGF-beta signaling in both the neurogenic and obstructive LUTD and highlighted FGF2 as a major upregulated transcription factor during organ remodeling. We conclude that SCI-induced DSD in mice leads to profound changes in neuronal signaling and muscle contractility, leading to bladder fibrosis. In a similar time frame, significant bladder remodeling following pBOO allowed for functional compensation, preserving normal micturition parameters.

Stimulation of the cuneiform nucleus enables training and boosts recovery after spinal cord injury.

Severe spinal cord injuries result in permanent paraparesis in spite of the frequent sparing of small portions of white matter. Spared fibre tracts are often incapable of maintaining and modulating the activity of lower spinal motor centres. Effects of rehabilitative training thus remain limited. Here, we activated spared descending brainstem fibres by electrical deep brain stimulation of the cuneiform nucleus of the mesencephalic locomotor region, the main control centre for locomotion in the brainstem, in adult female Lewis rats. We show that deep brain stimulation of the cuneiform nucleus enhances the weak remaining motor drive in highly paraparetic rats with severe, incomplete spinal cord injuries and enables high-intensity locomotor training. Stimulation of the cuneiform nucleus during rehabilitative aquatraining after subchronic (n = 8 stimulated versus n = 7 unstimulated versus n = 7 untrained rats) and chronic (n = 14 stimulated versus n = 9 unstimulated versus n = 9 untrained rats) spinal cord injury re-established substantial locomotion and improved long-term recovery of motor function. We additionally identified a safety window of stimulation parameters ensuring context-specific locomotor control in intact rats (n = 18) and illustrate the importance of timing of treatment initiation after spinal cord injury (n = 14). This study highlights stimulation of the cuneiform nucleus as a highly promising therapeutic strategy to enhance motor recovery after subchronic and chronic incomplete spinal cord injury with direct clinical applicability.

Lower urinary tract electrical sensory assessment: a systematic review and meta-analysis.

OBJECTIVES: To summarize the current literature on lower urinary tract electrical sensory assessment (LUTESA), with regard to current perception thresholds (CPTs) and sensory evoked potentials (SEPs), and to discuss the applied methods in terms of technical aspects, confounding factors, and potential for lower urinary tract (LUT) diagnostics. METHODS: The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Medline (PubMed), Embase and Scopus were searched on 13 October 2020. Meta-analyses were performed and methodological qualities of the included studies were defined by assessing risk of bias (RoB) as well as confounding. RESULTS: After screening 9925 articles, 80 studies (five randomized controlled trials [RCTs] and 75 non-RCTs) were included, comprising a total of 3732 patients and 692 healthy subjects (HS). Of these studies, 61 investigated CPTs exclusively and 19 reported on SEPs, with or without corresponding CPTs. The recording of LUTCPTs and SEPs was shown to represent a safe and reliable assessment of LUT afferent nerve function in HS and patients. LUTESA demonstrated significant differences in LUT sensitivity between HS and neurological patients, as well as after interventions such as pelvic surgery or drug treatments. Pooled analyses showed that several stimulation variables (e.g. stimulation frequency, location) as well as patient characteristics might affect the main outcome measures of LUTESA (CPTs, SEP latencies, peak-to-peak amplitudes, responder rate). RoB and confounding was high in most studies. CONCLUSIONS: Preliminary data show that CPT and SEP recordings are valuable tools to more objectively assess LUT afferent nerve function. LUTESA complements already established diagnostics such as urodynamics, allowing a more comprehensive patient evaluation. The high RoB and confounding rate was related to inconsistency and inaccuracy in reporting rather than the technique itself. LUTESA standardization and well-designed RCTs are crucial to implement LUTESA as a clinical assessment tool.

Intravesical bacteriophages for treating urinary tract infections in patients undergoing transurethral resection of the prostate: a randomised, placebo-controlled, double-blind clinical trial.

BACKGROUND: Urinary tract infections (UTIs) are among the most prevalent microbial diseases and their financial burden on society is substantial. In the context of increasing antibiotic resistance, finding alternative treatments for UTIs is a top priority. We aimed to determine whether intravesical bacteriophage therapy with a commercial bacteriophage cocktail is effective in treating UTI. METHODS: We did a randomised, placebo-controlled, clinical trial, at the Alexander Tsulukidze National Centre of Urology, Tbilisi, Georgia. Men older than 18 years of age, who were scheduled for transurethral resection of the prostate (TURP), with complicated UTI or recurrent uncomplicated UTI but no signs of systemic infection, were allocated by block randomisation in a 1:1:1 ratio to receive intravesical Pyo bacteriophage (Pyophage; 20 mL) or intravesical placebo solution (20 mL) in a double-blind manner twice daily for 7 days, or systemically applied antibiotics (according to sensitivities) as an open-label standard-of-care comparator. Urine culture was taken via urinary catheter at the end of treatment (ie, day 7) or at withdrawal from the trial. The primary outcome was microbiological treatment response after 7 days of treatment, measured by urine culture; secondary outcomes included clinical and safety parameters during the treatment period. Analyses were done in a modified intention-to-treat population of patients having received at least one dose of the allocated treatment regimen. This trial is registered with ClinicalTrials.gov, NCT03140085. FINDINGS: Between June 2, 2017, and Dec 14, 2018, 474 patients were screened for eligibility and 113 (24%) patients were randomly assigned to treatment (37 to Pyophage, 38 to placebo, and 38 to antibiotic treatment). 97 patients (28 Pyophage, 32 placebo, 37 antibiotics) received at least one dose of their allocated treatment and were included in the primary analysis. Treatment success rates did not differ between groups. Normalisation of urine culture was achieved in five (18%) of 28 patients in the Pyophage group compared with nine (28%) of 32 patients in the placebo group (odds ratio [OR] 1·60 [95% CI 0·45-5·71]; p=0·47) and 13 (35%) of 37 patients in the antibiotic group (2·66 [0·79-8·82]; p=0·11). Adverse events occurred in six (21%) of 28 patients in the Pyophage group compared with 13 (41%) of 32 patients in the placebo group (OR 0·36 [95% CI 0·11-1·17]; p=0·089) and 11 (30%) of 37 patients in the antibiotic group (0·66 [0·21-2·07]; p=0·47). INTERPRETATION: Intravesical bacteriophage therapy was non-inferior to standard-of-care antibiotic treatment, but was not superior to placebo bladder irrigation, in terms of efficacy or safety in treating UTIs in patients undergoing TURP. Moreover, the bacteriophage safety profile seems to be favourable. Although bacteriophages are not yet a recognised or approved treatment option for UTIs, this trial provides new insight to optimise the design of further large-scale clinical studies to define the role of bacteriophages in UTI treatment. FUNDING: Swiss Continence Foundation, the Swiss National Science Foundation, and the Swiss Agency for Development and Cooperation. TRANSLATIONS: For the Georgian and German translations of the abstract see Supplementary Materials section.

Effects of opioids and benzodiazepines on bladder function of awake restrained mice.

OBJECTIVE: We aimed to study the effects of anaesthetics on bladder function using repeated urodynamic investigation (UDI) including external urethral sphincter (EUS) electromyography (EMG) in awake restrained mice. MATERIALS AND METHODS: Female C57Bl/6J mice underwent either bladder catheter (n=6) or bladder catheter plus electrodes (n=10) implantation next to the EUS. A control group (n=3) was included for histological analysis. Following awake UDI, the effects of midazolam (5 mg/kg) and opioids (fentanyl (50 µg/kg) and hydromorphine (250 µg/kg)) on bladder function were studied. Mice were allowed to recover from drug application for at least one day before being subjected to the next drug and UDI. Bladder weight was assessed and fibrotic changes were analysed by Masson's trichrome staining. RESULTS: EUS-EMG activity during voiding was reduced compared to before and after voiding in baseline measurements. Threshold and maximal detrusor pressure were significantly increased in both midazolam and the opioids. The opioids lead to either a significantly increased bladder filling volume and micturition cycle duration (hydromorphine) or a complete loss of the voiding phase leading to overflow incontinence (fentanyl). Bladder-to bodyweight ratio was significantly increased in both groups with an implanted catheter compared to controls. No differences were observed between the groups with- or without implanted electrodes regarding bladder-to bodyweight ratio, bladder fibrosis and urodynamic parameters. CONCLUSIONS: Repeated UDIs combined with EUS-EMG are feasible in the awake mouse model. The presence of electrodes next to the EUS does not obstruct the bladder outlet. Opioids and benzodiazepines severely interfere with physiological bladder function: fentanyl and hydromorphine disrupted the voiding phase evidenced by the reduced coordination of EUS activity with detrusor contraction, while bladder emptying under midazolam was achieved by EUS relaxation only.

The Gigantocellular Reticular Nucleus Plays a Significant Role in Locomotor Recovery after Incomplete Spinal Cord Injury.

Traditionally, the brainstem has been seen as hardwired and poorly capable of plastic adaptations following spinal cord injury (SCI). Data acquired over the past decades, however, suggest differently: following SCI in various animal models (lamprey, chick, rodents, nonhuman primates), different forms of spontaneous anatomic plasticity of reticulospinal projections, many of them originating from the gigantocellular reticular nucleus (NRG), have been observed. In line with these anatomic observations, animals and humans with incomplete SCI often show various degrees of spontaneous motor recovery of hindlimb/leg function. Here, we investigated the functional relevance of two different modes of reticulospinal fiber growth after cervical hemisection, local rewiring of axotomized projections at the lesion site versus compensatory outgrowth of spared axons, using projection-specific, adeno-associated virus-mediated chemogenetic neuronal silencing. Detailed assessment of joint movements and limb kinetics during overground locomotion in female adult rats showed that locally rewired as well as compensatory NRG fibers were responsible for different aspects of recovered forelimb and hindlimb functions (i.e., stability, strength, coordination, speed, or timing). During walking and swimming, both locally rewired as well as compensatory NRG plasticity were crucial for recovered function, while the contribution of locally rewired NRG plasticity to wading performance was limited. Our data demonstrate comprehensively that locally rewired as well as compensatory plasticity of reticulospinal axons functionally contribute to the observed spontaneous improvement of stepping performance after incomplete SCI and are at least partially causative to the observed recovery of function, which can also be observed in human patients with spinal hemisection lesions.SIGNIFICANCE STATEMENT Following unilateral hemisection of the spinal cord, reticulospinal projections are destroyed on the injured side, resulting in impaired locomotion. Over time, a high degree of recovery can be observed in lesioned animals, like in human hemicord patients. In the rat, recovery is accompanied by pronounced spontaneous plasticity of axotomized and spared reticulospinal axons. We demonstrate the causative relevance of locally rewired as well as compensatory reticulospinal plasticity for the recovery of locomotor functions following spinal hemisection, using chemogenetic tools to selectively silence newly formed connections in behaviorally recovered animals. Moving from a correlative to a causative understanding of the role of neuroanatomical plasticity for functional recovery is fundamental for successful translation of treatment approaches from experimental studies to the clinics.

Complication reporting with the Bern Comprehensive Complication Index CCI after open radical prostatectomy: A longitudinal long-term single-center study.

OBJECTIVE: To impartially optimize complication reporting in patients after open radical prostatectomy (ORP) and pelvic lymph node dissection (PLND) by adopting the modified Bern Comprehensive Complication Index (CCI). ORP and PLND are associated with relevant postoperative morbidity. The CCI-ranging from 0 (no complications) to 100 (death)-is a tool that aims to integrate all complications occuring within 90 days postoperatively weighted by severity in a single formula. METHODS: In an observational single-center cohort, 90-day postoperative complications of 1,123 consecutive patients undergoing standardized ORP and PLND between 1996 and 2017 were evaluated. Prospectively collected complications were graded according to the Clavien-Dindo Classification. Grade I to II complications were defined as minor and grade IIIa to V as major. Finally, the recently developed modified Bern CCI using an exponential function, which transforms the sum of the weights into a value between 0 and 100 and the original CCI for each patient were extracted and compared. The correlation between the modified Bern and original CCI values was depicted graphically. RESULTS: The complication rate was 42%, with 18% minor and 24% major complications. With the original CCI, the threshold of 100 was exceeded in 1 patient who had a maximal index value of 101 within 90d postoperatively. The maximal value of the Bern CCI was 97.5. Mean Bern and original CCI scores and standard deviations were 6.2 (11.3) and 7.6 (12.2) at 30 days, and 9.3 (13.9) and 10.7 (14.2) at 90 days. CONCLUSIONS: The Bern CCI provides a more precise depiction of postoperative morbidity and represents the burden in patients with >1 complication after ORP and PLND more accurately than the original CCI allowing for a more reliable evaluation of quality of care and recovery. It therefore warrants consideration for standardized reporting of complications after ORP and PLND.

Benefits and Harms of Electrical Neuromodulation for Chronic Pelvic Pain: A Systematic Review.

CONTEXT: Patients with chronic pelvic pain (CPP) may have pain refractory to conventional pain management strategies. Neuromodulation could provide relief of pain. OBJECTIVE: To evaluate the benefits and harms of neuromodulation for CPP. EVIDENCE ACQUISITION: A comprehensive search of EMBASE, PUBMED, and SCOPUS was performed for the entire database to January 2018. Studies were selected, data were extracted, and quality was assessed by two independent reviewers. A meta-analysis was used to combine randomized controlled trials (RCTs); otherwise, a narrative analysis was used. EVIDENCE SYNTHESIS: After screening 1311 abstracts, 36 studies including eight RCTs were identified, enrolling 1099 patients. Studies covered a broad range in terms of phenotypes of CPP and methods of neuromodulation. A meta-analysis was possible for percutaneous tibial nerve stimulation and transcutaneous electrical nerve stimulation, which showed improvement in pain. Only narrative synthesis was possible for other modalities (sacral nerve stimulation, spinal cord stimulation, intravaginal electrical stimulation, and pudendal nerve stimulation) which appeared to reduce pain in patients with CPP. Treatments generally improved quality of life but with variable reporting of adverse events. Many studies showed high risks of bias and confounding. CONCLUSIONS: While electrical neuromodulation may improve symptoms in CPP, further work is needed with high-quality studies to confirm it. PATIENT SUMMARY: Neuromodulation may be useful in reducing pain and improving quality of life in patients with chronic pelvic pain, but more research is needed.

Comparison of the Diagnostic Performance of Contrast-enhanced Ultrasound with That of Contrast-enhanced Computed Tomography and Contrast-enhanced Magnetic Resonance Imaging in the Evaluation of Renal Masses: A Systematic Review and Meta-analysis.

CONTEXT: Contrast-enhanced ultrasound (CEUS) has the potential to be a valuable alternative to contrast-enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance imaging (CEMR), the current gold standards in characterisation of renal masses. OBJECTIVE: To systematically review all available evidence on the qualitative diagnostic performance of CEUS versus that of CECT and CEMR in the evaluation of benign and malignant cystic and solid renal masses. EVIDENCE ACQUISITION: The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. EVIDENCE SYNTHESIS: After screening 1483 articles, six cohort studies and 10 descriptive studies were included. Pooling data from included studies with final diagnosis of benign or malignant renal masses by pathology showed a significant difference in the sensitivity of CEUS (0.96; 95% confidence interval [CI] 0.94-0.98) versus that of CECT (0.90; 95% CI 0.86-0.93). Pooling data from included studies with final diagnosis by pathology report or reaffirmed diagnosis by follow-up imaging without pathology report showed significant difference in the sensitivity of CEUS (0.98; 95% CI 0.94-1.0) versus that of CEMR (0.78; 95% CI 0.66-0.91). CONCLUSIONS: Preliminary data imply that CEUS may perform at least as well as or better than CECT and CEMR in the diagnosis of renal masses. However, the evidence base is limited, and more high-quality, well-designed, adequately powered, and sampled studies are needed to reach definitive conclusions. PATIENT SUMMARY: Early data suggest that contrast-enhanced ultrasound is a promising option for the evaluation of renal masses, but more reliable evidence is required.

Bowel Outcome Prediction After Traumatic Spinal Cord Injury: Longitudinal Cohort Study.

Background. Predicting functional outcomes after traumatic spinal cord injury (SCI) is essential for counseling, rehabilitation planning, and discharge. Moreover, the outcome prognosis is crucial for patient stratification when designing clinical trials. However, no valid prediction rule is currently available for bowel outcomes after a SCI. Objective. To generate a model for predicting the achievement of independent, reliable bowel management at 1 year after traumatic SCI. Methods. We performed multivariable logistic regression analyses of data for 1250 patients with traumatic SCIs that were included in the European Multicenter Study about Spinal Cord Injury. The resulting model was prospectively validated on data for 186 patients. As potential predictors, we evaluated age, sex, and variables from the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) and the Spinal Cord Independence Measure (SCIM), measured within 40 days of the injury. A positive outcome at 1 year post-SCI was assessed with item 7 of the SCIM. Results. The model relied on a single predictor, the ISNCSCI total motor score-that is, the sum of muscle strengths in 5 key muscle groups in each limb. The area under the receiver operating characteristics curve (aROC) was 0.837 (95% CI: 0.815-0.859). The prospective validation confirmed high predictive power: aROC = 0.817 (95% CI: 0.754-0.881). Conclusions. We generated a valid model for predicting independent, reliable bowel management at 1 year after traumatic SCI. Its application could improve counseling, optimize patient-tailored rehabilitation planning, and become crucial for appropriate patient stratification in future clinical trials.

Alpha-blockers for treating neurogenic lower urinary tract dysfunction in patients with multiple sclerosis: A systematic review and meta-analysis. A report from the Neuro-Urology Promotion Committee of the International Continence Society (ICS).

AIM: We aimed to systematically assess the evidence on the efficacy and safety of alpha-blockers in patients with multiple sclerosis (MS) suffering from neurogenic lower urinary tract dysfunction (NLUTD). METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used to perform this systematic review. An electronic search of Cochrane register, Embase, Medline, Scopus (last search 3 March 2018) and screening of reference lists as well as reviews were used to identify the studies. Articles were included if they reported on efficacy/safety of alpha-blockers for the treatment of NLUTD in patients with MS. RESULTS: After screening of 7'015 abstracts, three studies enrolling a total of 50 patients were included: one randomized, placebo-controlled, single-blind trial and two prospective cohort studies. Alpha-blocker treatment was successful in 50% to 96% of the patients. Pooling data from the three included studies, the relative risk for successful alpha-blocker treatment was 3.89 (95% confidence interval 2.7-7.0). The general safety profile of alpha-blockers was favorable with 8% of the patients reporting adverse events. CONCLUSIONS: Alpha-blockers may be effective and safe for treating NLUTD in female and male patients with MS but the studies were small and the overall quality of evidence was low. To make definitive conclusions, well designed randomized controlled trials are highly warranted.

Anti-Nogo-A Antibodies As a Potential Causal Therapy for Lower Urinary Tract Dysfunction after Spinal Cord Injury.

Loss of bladder control is common after spinal cord injury (SCI) and no causal therapies are available. Here we investigated whether function-blocking antibodies against the nerve-fiber growth inhibitory protein Nogo-A applied to rats with severe SCI could prevent development of neurogenic lower urinary tract dysfunction. Bladder function of rats with SCI was repeatedly assessed by urodynamic examination in fully awake animals. Four weeks after SCI, detrusor sphincter dyssynergia had developed in all untreated or control antibody-infused animals. In contrast, 2 weeks of intrathecal anti-Nogo-A antibody treatment led to significantly reduced aberrant maximum detrusor pressure during voiding and a reduction of the abnormal EMG high-frequency activity in the external urethral sphincter. Anatomically, we found higher densities of fibers originating from the pontine micturition center in the lumbosacral gray matter in the anti-Nogo-A antibody-treated animals, as well as a reduced number of inhibitory interneurons in lamina X. These results suggest that anti-Nogo-A therapy could also have positive effects on bladder function clinically.SIGNIFICANCE STATEMENT After spinal cord injury, loss of bladder control is common. Detrusor sphincter dyssynergia is a potentially life-threatening consequence. Currently, only symptomatic treatment options are available. First causal treatment options are urgently needed in humans. In this work, we show that function-blocking antibodies against the nerve-fiber growth inhibitory protein Nogo-A applied to rats with severe spinal cord injury could prevent development of neurogenic lower urinary tract dysfunction, in particular detrusor sphincter dyssynergia. Anti-Nogo-A therapy has entered phase II clinical trial in humans and might therefore soon be the first causal treatment option for neurogenic lower urinary tract dysfunction.

Remyelination promoting therapies in multiple sclerosis animal models: a systematic review and meta-analysis.

An unmet but urgent medical need is the development of myelin repair promoting therapies for Multiple Sclerosis (MS). Many such therapies have been pre-clinically tested using different models of toxic demyelination such as cuprizone, ethidium bromide, or lysolecithin and some of the therapies already entered clinical trials. However, keeping track on all these possible new therapies and their efficacy has become difficult with the increasing number of studies. In this study, we aimed at summarizing the current evidence on such therapies through a systematic review and at providing an estimate of the effects of tested interventions by a meta-analysis. We show that 88 different therapies have been pre-clinically tested for remyelination. 25 of them (28%) entered clinical trials. Our meta-analysis also identifies 16 promising therapies which did not enter a clinical trial for MS so far, among them Pigment epithelium-derived factor, Plateled derived growth factor, and Tocopherol derivate TFA-12.We also show that failure in bench to bedside translation from certain therapies may in part be attributable to poor study quality. By addressing these problems, clinical translation might be smoother and possibly animal numbers could be reduced.

Desmopressin for treating nocturia in patients with multiple sclerosis: A systematic review: A report from the Neuro-Urology Promotion Committee of the International Continence Society (ICS).

AIMS: To systematically assess all available evidence on efficacy and safety of desmopressin for treating nocturia in patients with multiple sclerosis (MS). METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were identified by electronic search of Cochrane register, Embase, Medline, Scopus (last search March 3, 2018) and by screening of reference lists and reviews. RESULTS: After screening of 7015 abstracts, 8 prospective, and 1 retrospective studies were included enrolling a total of 178 patients. The mean patient age ranged between 43 and 51 years. A significant decrease in the number of micturitions per night was reported in 5 studies. An increase in the maximum hours of uninterrupted sleep was only found in two studies. A significant reduction of the volume of nocturnal incontinence was described in one study. The patient satisfaction rates ranged from 56% to 82%. The rate of adverse events was between 0% and 57.9%. The rate of hyponatremia ranged from 0% to 23.5% and other commonly reported adverse events were headache, nausea, fluid retention, rhinitis/epistaxis, malaise, and swollen ankles. Risk of bias and confounding was relevant in all studies. CONCLUSIONS: Preliminary data suggest that desmopressin might be effective for treating nocturia in patients with MS. However, adverse events are relatively common, the overall quality of evidence is low and the number of studied patients is very limited. Further studies with newer formulations of desmopressin are highly warranted.

Cardiac electrophysiology catheters for electrophysiological assessments of the lower urinary tract-A proof of concept ex vivo study in viable ureters.

AIMS: To explore the feasibility of minimally invasive catheter-based electrophysiology studies in the urinary tract. This is a well-known method used in cardiology to investigate and treat arrhythmias. METHODS: We developed an experimental platform which allows electrophysiological recordings with cardiac catheters and conventional needle electrodes in ex vivo pig ureters. The action potential was triggered by a stimulating electrode. We considered 13 porcine ureters (freshly collected and harvested in organ bath), 7 of which were used to optimize the setup and define the stimulation parameters; we performed the recordings in the remaining six ureters. The electrical propagation of the generated action potential was tracked with multiple sensing electrodes, from which propagation directions, velocities, refractory periods, and pacing thresholds were extracted. RESULTS: We recorded propagating electrical activity in four ureters using needle electrodes and in two ureters using cardiac catheters. Propagation velocities for forward direction (from kidney to bladder) derived by the two methods were similar (15.1 ± 2.6 mm/s for cardiac catheters, 15.6 ± 2.3 mm/s for needle recordings). Pacing thresholds, activation patters, and refractory times were provided for the ureteric smooth muscle. Retrograde propagations and corresponding velocities were also observed and measured. CONCLUSIONS: This study is a proof-of-concept showing that electrical activity can be measured "from the inside" of urinary cavities using catheters and that obtained results are comparable with the more invasive needle recordings. Catheter-based electrophysiology may allow, in the clinical setting, for: i) a more differentiated understanding of urological disorders such as overactive bladder and ii) new therapeutic approaches (e.g., targeted tissue ablation).

Catheterization for treating neurogenic lower urinary tract dysfunction in patients with multiple sclerosis: A systematic review. A report from the Neuro-Urology Promotion Committee of the International Continence Society (ICS).

AIM: To systematically assess all available evidence on efficacy and safety of catheterization for treating neurogenic lower urinary tract dysfunction (NLUTD) in patients with multiple sclerosis (MS). METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were identified by electronic search of Embase, Medline, Scopus, Cochrane register (last search March 3, 2018) and by screening of reference lists and reviews. RESULTS: After screening 7'015 articles, we included four studies (one prospective and two retrospective cohort studies, one retrospective cross-sectional study), in which a total of 445 patients were enrolled. No randomized controlled trial was available. Catheterization substantially increased quality of life, post void residual, and incontinence episodes in all included studies. Pooling of data for meta-analysis was not possible due to the heterogeneity of reported outcomes. Adverse events were reported in two studies only. Risk of bias and confounding was intermediate. CONCLUSIONS: Preliminary data suggests beneficial effects of catheterization on the urological outcome in patients with MS. However, although intermittent and indwelling catheterization is used frequently in daily clinical practice in the MS population, the evidence base is very limited and well-designed, properly sampled, and powered studies are urgently needed.

Early urological care of patients with spinal cord injury.

PURPOSE: After spinal cord injury (SCI), the initial goals of urological management include maintaining safe storage of urine with efficient bladder emptying, maximising urinary continence, and minimising the risk of urological complications. METHODS: This review was performed according to the methodology recommended by the Joint SIU-ICUD International Consultation. Embase and Medline databases were used to identify literature relevant to the early urological care of SCI patients. Recommendations were developed by consensus and graded using a modified Oxford system which identifies level of evidence (LOE) and grade of recommendation (GOR). RESULTS: Clinicians must ensure appropriate bladder emptying immediately after SCI (LOE 3, GOR A) and perform the initial neuro-urological assessment within 3 months after injury (LOE 3, GOR A), including history, validated questionnaires, bladder diary, physical examination, measurement of renal function, and urinary tract imaging (LOE 4, GOR B). Urodynamics, if available video-urodynamics, must be performed to detect and specify lower urinary tract dysfunction (LOE 1, GOR A). Spontaneous voiding and/or intermittent catheterization must be considered in appropriate patients once they are medically stable (LOE 3, GOR A). Antimuscarinics are the first-line and intradetrusor botulinum toxin A injections are the second-line treatment for neurogenic detrusor overactivity (LOE 1, GOR A). Irreversible surgical interventions should be delayed until the second year after injury due to the potential for neurological recovery (LOE 4, GOR B). CONCLUSIONS: Careful clinical assessment and pertinent urological testing including urodynamic investigation are necessary for appropriate counselling and treatment of new SCI patients.

Early neurological care of patients with spinal cord injury.

PURPOSE: Considering the major clinical challenges of managing patients with spinal cord injury (SCI), we summarized the relevant aspects of the early (within 1 year after SCI) neurological care emphasizing common standards. METHODS: This review was performed according to the methodology recommended by the Joint SIU-ICUD International Consultation. Embase and Medline databases were used to identify literature relevant to the early neurological care of SCI patients. Recommendations were developed by consensus and graded using a modified Oxford system which identifies level of evidence (LOE) and grade of recommendation (GOR). RESULTS: Emergency health care providers must address altered mental status, evidence of intoxication, suspected extremity fracture/distracting injury, focal neurological deficit and spinal pain/tenderness to determine the risk of SCI in a trauma patient [LOE 1, GOR A]. Neurogenic shock must be recognized and treated [LOE 3, GOR A]. Spine surgeons should consider early decompression and spine fixation/stabilization, where indicated, and should promote early active rehabilitation to improve functional recovery [LOE 2, GOR B]. Clinicians should refer SCI patients to specialized SCI rehabilitation centers [LOE 4, GOR B], must apply interventions to prevent venous thromboembolism (i.e., compression devices and low-molecular weight heparin/unfractionated heparin) after acute SCI respecting contraindications [LOE 1, GOR A]. Contemporary guidelines to manage pain must be employed [LOE 1, GOR A] and methods to reduce the risk of pressure ulcers should be used [LOE 3, GOR B]. CONCLUSIONS: Early treatment, prevention of associated complications and individualized patient-targeted rehabilitation programs provided by a specialized interdisciplinary team are crucial to optimize the outcome after SCI.

Impact of intra-operative fluid and noradrenaline administration on early postoperative renal function after cystectomy and urinary diversion: A retrospective observational cohort study.

BACKGROUND: The use of noradrenaline to enable a restrictive approach to intra-operative fluid therapy to avoid salt and water overload has gained increasing acceptance. However, concerns have been raised about the impact of this approach on renal function. OBJECTIVES: To identify risk factors for acute kidney injury (AKI) in patients undergoing cystectomy with urinary diversion and determine whether administration of noradrenaline and intra-operative hydration regimens affect early postoperative renal function. DESIGN: Retrospective observational cohort study. SETTING: University hospital, from 2007 to 2016. PATIENTS: A total of 769 consecutive patients scheduled for cystectomy and urinary diversion. Those with incomplete data and having pre-operative haemodialysis were excluded. MAIN OUTCOME MEASURES: AKI was defined as a serum creatinine increase of more than 50% over 72 postoperative hours. Multiple logistic regression analysis was performed to model the association between risk factors and AKI. RESULTS: Postoperative AKI was diagnosed in 86/769 patients (11.1%). Independent predictors for AKI were the amount of crystalloid administered (odds ratio (OR) 0.79 [95% confidence interval (CI), 0.68 to 0.91], P = 0.002), antihypertensive medication (OR 2.07 [95% CI, 1.25 to 3.43], P = 0.005), pre-operative haemoglobin value (OR 1.02 [95% CI, 1.01 to 1.03], P = 0.010), duration of surgery (OR 1.01 [95% CI, 1.00 to 1.01], P = 0.002), age (OR 1.32 [95% CI, 1.44 to 1.79], P = 0.002) but not the administration of noradrenaline (OR 1.09 [95% CI, 0.94 to 1.21], P = 0.097). Postoperative AKI was associated with longer hospital stay (18 [15 to 22] vs. 16 [15 to 19] days; P = 0.035) and a higher 90-day major postoperative complication rate (41.9 vs. 27.5%; P = 0.002). CONCLUSION: Noradrenaline administration did not increase the risk for AKI. A too restrictive approach to administration of crystalloids was associated with an increased risk for AKI, particularly in older patients, those receiving antihypertensive medication, and those whose surgery was prolonged. As AKI was associated with longer hospital stay and increased postoperative morbidity, these observations should be taken into account to improve outcome when addressing peri-operative fluid management. TRIAL REGISTRATION: Not applicable.