Prophylactic intravenous gentamicin with sedation-free cystoscopic injection of BoNT-A: No demonstrable adverse extravesical neuromuscular effects in a pilot safety study of 220 idiopathic overactive bladder patients

Objectives: To determine whether administration of single dose prophylactic intravenous gentamicin prior to intravesical injection of botulinum toxin type A (BoNT-A) is associated with adverse extravesical neuromuscular effects in idiopathic overactive bladder syndrome. Patients and methods: A retrospective analysis of 220 consecutive idiopathic overactive bladder patients following sedation-free flexible cystoscopic injection of intravesical BoNT-A. All patients received a single dose of intravenous gentamicin (160 mg) followed by 100-200 IU of BoNT-A. They were followed up at intervals to determine whether they had experienced any adverse extravesical neuromuscular side effects. Results: None of our patients developed adverse extravesical neuromuscular side effects from intravesical botulinum injections with concomitant administration of intravenous gentamicin. Conclusion: Single dose intravenous gentamicin is safe to use as a prophylaxis for intravesical BoNT-A injections of 200 IU or below in idiopathic overactive bladder patients. Level of evidence: Not applicable.

Swarming behavior and in vivo monitoring of enzymatic nanomotors within the bladder

Enzyme-powered nanomotors are an exciting technology for biomedical applications due to their ability to navigate within biological environments using endogenous fuels. However, limited studies into their collective behavior and demonstrations of tracking enzyme nanomotors in vivo have hindered progress toward their clinical translation. Here, we report the swarming behavior of urease-powered nanomotors and its tracking using positron emission tomography (PET), both in vitro and in vivo. For that, mesoporous silica nanoparticles containing urease enzymes and gold nanoparticles were used as nanomotors. To image them, nanomotors were radiolabeled with either 124I on gold nanoparticles or 18F-labeled prosthetic group to urease. In vitro experiments showed enhanced fluid mixing and collective migration of nanomotors, demonstrating higher capability to swim across complex paths inside microfabricated phantoms, compared with inactive nanomotors. In vivo intravenous administration in mice confirmed their biocompatibility at the administered dose and the suitability of PET to quantitatively track nanomotors in vivo. Furthermore, nanomotors were administered directly into the bladder of mice by intravesical injection. When injected with the fuel, urea, a homogeneous distribution was observed even after the entrance of fresh urine. By contrast, control experiments using nonmotile nanomotors (i.e., without fuel or without urease) resulted in sustained phase separation, indicating that the nanomotors’ self-propulsion promotes convection and mixing in living reservoirs. Active collective dynamics, together with the medical imaging tracking, constitute a key milestone and a step forward in the field of biomedical nanorobotics, paving the way toward their use in theranostic applications.

Therapeutic Effect of Botulinum Toxin A on Sensory Bladder Disorders—From Bench to Bedside

Bladder oversensitivity arises from several different conditions involving the bladder, bladder outlet, systemic or central nervous system diseases. Increase of the bladder sensation results from activation of the sensory receptors in the urothelial cells or suburothelial tissues. Medical treatment targeting the overactive bladder (OAB) or interstitial cystitis (IC) might relieve oversensitive bladder symptoms (frequency, urgency and pain) in a portion of patients, but a certain percentage of patients still need active management. Botulinum toxin A (BoNT-A) has been demonstrated to have anti-inflammatory and antinociceptive effects in bladder sensory disorders and has been shown effective in the reduction of bladder oversensitivity and the increase of functional bladder capacity. For patients with OAB, urgency and urinary incontinence improved, while in patients with IC, bladder pain could be relieved in association with reduction of bladder oversensitivity after BoNT-A intravesical injection. Histological evidence has confirmed the therapeutic mechanism and clinical efficacy of intravesical BoNT-A injection on patients with OAB or IC. Bladder oversensitivity can also be relieved with the instillation of liposome encapsulated BoNT-A or low energy show waves (LESWs), which enable the BoNT-A molecule to penetrate into the urothelium and suburothelial space without affecting the detrusor contractility. Liposome encapsulated BoNT-A or combined LESWs and BoNT-A instillation might be future treatment alternatives for bladder oversensitivity in sensory bladder disorders.

The intravesical injection of highly purified botulinum toxin for the treatment of neurogenic detrusor overactivity

Introduction: We aimed to assess safety and efficacy of incobotulinumtoxinA for the treatment of neurogenic detrusor overactivity (DO). Methods: We identified patients with neurogenic DO confirmed on urodynamics (UDS) and reported urgency incontinence (UI) in those who received intravesical incobotulinumtoxin A injection for neurogenic bladder between November 2013 and May 2017. Parameters studied were daytime frequency, daily incontinence episodes, daily pad use, clean intermittent catheterization (CIC) volumes, symptom scores (UDI6, IIQ7, PGII), and complications. Results: We examined 17 male patients who met inclusion criteria and underwent incobotulinumtoxinA injection. Mean age was 61.2±15.4 years. Fourteen patients (82%) were taking oral antimuscarinics prior to the incobotulinumtoxin A injection. There were improvements in the following parameters: average daily pads (4.5 to 3.3, p=0.465), daily urinary frequency (9.4 to 4.6, p=0.048), daily incontinent episodes (2.5 to 0.4, p=0.033), CIC volumes (400 to 550 mL, p=0.356), hours in between CIC (3.6 to 5.2, p=0.127), and the validated questionnaires UDI6 (30.6 to 7.4, p=0.543) and IIQ7 (52.4 to 6.8, p=0.029). There were no documented symptomatic urinary tract infections (UTIs) within 30 days of injection or reports of de novo urinary retention. Nine of 17 patients (53%) reported being dry at their first postoperative visit. Conclusions: In this preliminary pilot study of a small cohort of males with neurogenic DO and UI, significant improvements were seen following incobotulinumtoxinA injection in daily frequency, incontinence episodes, hours in between CIC, and quality of life. Larger-scale and long-term studies are required to confirm these results, but initial findings are promising for wider use of this formulation.

Predictive Factors for a Satisfactory Treatment Outcome with Intravesical Botulinum Toxin A Injection in Patients with Interstitial Cystitis/Bladder Pain Syndrome

A botulinum toxin A (BoNT-A) intravesical injection can improve the symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS). Patients with IC/BPS have different clinical characteristics, urodynamic features, and cystoscopic findings. This study assessed the treatment outcomes of a BoNT-A intravesical injection and aimed to identify the predictive factors of a satisfactory outcome. This retrospective study included IC/BPS patients treated with 100 U BoNT-A. The treatment outcomes were assessed by global response assessment (GRA) at 6 months. We classified patients according to different clinical, urodynamic, and cystoscopic characteristics and evaluated the treatment outcomes and predictive factors. A total of 238 patients were included. Among these patients, 113 (47.5%) had a satisfactory outcome (GRA ≥ 2) and 125 (52.5%) had an unsatisfactory outcome. Improvements in the IC symptom score, IC problem score, O’Leary–Sant symptom score, and visual analog scale score for pain were significantly greater in patients with a satisfactory outcome than in patients with an unsatisfactory outcome (all p = 0.000). The IC disease duration and maximal bladder capacity (MBC) were significantly different between patients with and without a satisfactory outcome. Multivariate analysis revealed that only the MBC was a predictor for a satisfactory outcome. Patients with a MBC of ≥760 mL and glomerulations of 0/1 (58.7%) or glomerulations of 2/3 (75.0%) frequently had a satisfactory outcome. We found that BoNT-A intravesical injection can effectively improve symptoms among patients with IC/BPS, with a remarkable reduction in bladder pain. A MBC of ≥760 mL is a predictive factor for a satisfactory treatment outcome.