A prospective study to assess the effectiveness and safety of the BlueWind System in the treatment of patients diagnosed with urgency urinary incontinence.

BACKGROUND: Overactive bladder (OAB) affects one in six adults in Europe and the United States and impairs the quality of life of millions of individuals worldwide. When conservative management fails, third-line treatments including tibial neuromodulation (TNM) is often pursued. TNM has traditionally been accomplished percutaneously in clinic. OBJECTIVE: A minimally invasive implantable device activated by a battery-operated external wearable unit has been developed for the treatment of urgency urinary incontinence (UUI), mitigating the burden of frequent clinic visits and more invasive therapies that are currently commercially available. METHODS: A prospective, multicenter, single-arm, open-label, pivotal study evaluated the safety and effectiveness of the device in adult females with UUI (i.e., wet OAB) (BlueWind Implantable Tibial Neuromodulation [iTNM] system; IDE number #G200013; NCT03596671). Results with the device were previously published under the name RENOVA iStim, which has been since renamed as the Revi™ System. Approximately 1-month post-implantation of the device, participants delivered therapy at their convenience and completed a 7-day voiding diary before visits 6- and 12-months post-treatment initiation. The primary efficacy and safety endpoints were the proportion of responders to therapy ( ≥ 50% improvement on average number of urgency-related incontinence episodes) and incidence of adverse events from implantation to 12-month post-activation. RESULTS: A total of 151 participants, mean age 58.8 (SD: 12.5), were implanted; 144 and 140 completed the 6- and 12-month visits, respectively. The participants demonstrated mean baseline of 4.8 UUI/day (SD 2.9) and 10 voids/day (SD 3.3). Six and 12-months post-activation, 76.4% and 78.4% of participants, respectively, were responders to therapy in an intent-to-treat analysis. Of the 139 participants with completed 12-month diaries, 82% were responders, 50% were classified as "dry" (on at least 3 consecutive diary days), and 93.5% of participants reported that their symptoms improved. No implanted participant experienced an SAE related to the procedure or device. CONCLUSIONS: iTNM, delivered and powered by a patient-controlled external wearable communicating with an implant, demonstrated clinically meaningful and statistically significant improvement in UUI symptoms and a high safety profile. This therapy highlights the value of patient-centric therapy for the treatment of UUI.

Randomized prospective crossover study of interstim lead wire placement with curved versus straight stylet.

AIMS: To assess whether InterStim lead wire placement with the curved stylet achieves motor response at lower amplitudes compared to straight stylet use. METHODS: This was a prospective, randomized, crossover study of patients scheduled for InterStim lead wire placement. All patients underwent lead wire testing with both the curved and straight stylets. Patients were randomized to determine stylet order, and then crossed-over to the alternate. Intra-operatively, the amplitude achieving motor response at each electrode was recorded. The stylet with lowest overall amplitudes was used for final placement. Primary outcome measure was amplitude requirement in the two deepest (0 and 1) electrodes. Secondary outcomes included amplitudes at the number 2 and 3 electrodes, combined amplitudes, stylet order, and adverse outcomes. RESULTS: Forty-two patients were enrolled, 40 of whom were included in the final analysis. Mean age was 69 years (SD = 12.8) and mean BMI 27 (SD = 5.6). Indications for placement included: urge urinary incontinence (N = 26), urge/frequency (N = 25), non-obstructive urinary retention (N = 5), and fecal incontinence (N = 10). There were no significant differences between randomized groups. Regardless of order, the curved stylet achieved a motor response at lower amplitudes in the deepest electrodes (P < 0.001). Combined amplitudes of all electrodes were also significantly lower with the curved stylet (P < 0.001). Subsequently, 88% underwent final "optimal" placement with curved stylet (N = 35). CONCLUSIONS: The curved stylet for InterStim lead wire placement consistently achieved motor response at lower amplitudes. A brief intra-operative exchange of stylets represents a minor procedural alteration that could maximize Implantable Pulse Generator battery life and facilitate programming.

In vivo recovery of the injured anal sphincter after repair and injection of myogenic stem cells: an experimental model.

OBJECTIVE: This study aims to evaluate in vivo function of the external anal sphincter after transection and repair augmented with myogenic stem cells, and to establish normative electromyography parameters of the rodent external anal sphincter. DESIGN AND SETTING: Thirty-three Sprague-Dawley rodents underwent baseline needle electromyography of the external anal sphincter. Motor unit action potentials were obtained and normative parameters established. Animals were randomly assigned to a myogenic stem cell group (n = 24) or control group (n = 9). All underwent proctoepisiotomy. The control group underwent layered repair with phosphate-buffered saline injection to the external anal sphincter. The treatment group underwent identical repair with injection of myogenic stem cells 5.0 × 10. Baseline anal pressure recordings were collected and repeated 2 weeks postintervention, and electromyography was repeated at 2 and 4 weeks. Groups were compared across 3 time points with the use of repeated measures ANOVA. MAIN OUTCOME MEASURES: The primary outcomes measured were the functional recovery of rat anal sphincters after stem cell transplantation as assessed by objective electromyography and anal pressure measures. RESULTS: A mean of 17 motor unit action potentials were sampled per animal. At 2 weeks postrepair, there was a significant difference between control and transplant groups with respect to amplitude, duration, turns, and phases (p < 0.01 for each). No significant electromyography differences were seen at 4 weeks. Resting and peak anal pressures declined significantly at 2 weeks postinjury in the control but not in the stem cell group. LIMITATIONS: Use of a murine animal population limited the subjective feedback and wider applicability. CONCLUSIONS: In vivo functional studies show recovery of anal sphincter pressures and electromyography to preinjury levels by day 14 in the myogenic stem cell group but not controls. At 4 weeks, all electromyography parameters returned to baseline irrespective of group. Restoration of function may be accelerated by the transplantation of myogenic stem cells and associated trophic factors.

Stem cells in gynecology.

Stem cell based therapies hold promise for the obstetrician and gynecologist. This article reviews the history of stem cells and some of their current applications in gynecology. Currently, mesenchymal and muscle-derived stem cells are being explored for the treatment of urinary and anal incontinence. Potential stem cell treatments include fistula repair, vaginal tissue engineering, and graft material enhancement. Published animal and human pilot studies demonstrate improved histologic and functional outcomes in those receiving stem cells. Transplanted cells may improve function by local engraftment, trophic factors, or modulation of inflammation. Further clinical and safety studies are needed before clinical application.

Ischiorectal fossa abscess after pelvic floor injection of botulinum toxin.

Botulinum toxin is used to treat pelvic floor tension myalgia; however, its safety profile is poorly understood. We report an ischiorectal fossa abscess after pelvic floor injections of botulinum toxin. Physicians need to be aware of this possible complication, consider alternate injection techniques and antiseptic preparation before injection.

Effects of the incontinence dish pessary on urethral support and urodynamic parameters.

OBJECTIVE: To evaluate the effects of the incontinence dish pessary (IDP) on urethral mobility and urodynamics. STUDY DESIGN: Prospective study of women with symptoms of stress incontinence. Q-tip test was performed recording the resting and straining angles with and without an IDP. Changes in resting and straining angles were calculated. Those with evidence of urodynamic stress incontinence had urodynamics with the IDP. Paired t-test was used to compare the difference in Q-tip angles with and without the pessary. RESULTS: Mean Q-tip straining angle without and with the pessary, respectively, was 57.8 (+19.5) and 34.4 (+29.7). Mean change was 23.5 (+18.5) P < .00001. Maximum urethral closure pressure (MUCP) was significantly increased by 19.7 cm H(2)0 P < .001. Overall, 60% of the subjects did not leak with the IDP. CONCLUSION: The IDP eliminates >60% of USI. The mechanism of action may be a combination of improved UVJ support and increased MUCP.

Reconstructive pelvic surgery and plastic surgery: safety and efficacy of combined surgery.

OBJECTIVE: The purpose of this study was to address the safety of combining aesthetic and pelvic floor reconstructive procedures. STUDY DESIGN: Fifty-four subjects were included in a case-control study; 18 patients undergoing combined pelvic and plastic reconstructive surgery, age and procedure matched to 18 pelvic surgery and 18 plastic surgery only controls. Chi-square, t test, and Kruskal-Wallis analysis were used to compare the estimated blood loss (EBL), body mass index (BMI), hospital days, operative times, and complications between the groups. RESULTS: No differences were seen with regards to age, BMI, or EBL. There was, however, a significant increase in minor complications and hospital stay after combined procedures relative to the pelvic surgery control group but not the aesthetic control group. Operative times were only greater during combined procedures relative to isolated pelvic floor procedures. CONCLUSION: Combining pelvic and aesthetic procedures may increase complications, operative times, and length of hospital stay when compared to pelvic reconstructive surgery alone.

Sacral nerve neuromodulation in patients with cardiac pacemakers.

OBJECTIVE: The objective of the study was to describe our experience using sacral nerve neuromodulation for urinary urgency, frequency, and urge incontinence in patients with cardiac pacemakers. STUDY DESIGN: The study was a case series of 3 patients with cardiac pacemakers who underwent sacral nerve stimulation for refractory urgency, frequency, and urge incontinence. RESULTS: Each patient underwent placement of an InterStim lead wire in the S3 foramen. Intraoperative cardiac monitoring revealed no evidence of cross-interference, even at maximum stimulation. Postoperative telemetry for 24 hours did not reveal any interference from the sacral nerve stimulator. All patients had a greater than 50% reduction in incontinence episodes during their test trial and underwent placement of the InterStim implantable pulse generator (IPG). Intraoperative and postoperative IPG programming was done with cardiac monitoring; no interaction was detectable. CONCLUSION: Sacral nerve stimulation appears to be safe in the presence of a cardiac pacemaker.

Sacral nerve neuromodulation in patients with underlying neurologic disease.

OBJECTIVE: Sacral nerve neuromodulation (SNS) is an effective treatment for lower urinary tract dysfunction. Many underlying neurologic processes affect lower urinary tract function. We present results of SNS in patients with underlying neurologic dysfunction. STUDY DESIGN: This is a retrospective case series of 33 patients with neurologic disease and lower urinary tract dysfunction who underwent an InterStim stimulation procedure. Results were evaluated by pre- and postoperative voiding diaries. Success was defined as greater than 50% improvement. RESULTS: Twenty-eight of 33 patients (85%) underwent implantation: 13 of 16 (81%) multiple sclerosis, 4 of 6 (67%) Parkinson disease, and 11 of 11 (100%) other neurologic disorders. Incontinence episodes per 24 hours decreased 68%, number of voids per 24 hours decreased 43%, nocturia decreased 70%, and there was a 58% reduction in intermittent self-catheterization per 24 hours. Ninety-three percent reported overall satisfaction. CONCLUSION: Sacral nerve neuromodulation is an effective treatment for lower urinary tract dysfunction in patients with underlying neurologic disease.

Repairing perineal hernia.

The patient's pelvic structures repeatedly shifted out of place. Her physicians found a fix that helped.

Surgical Case Logging Habits and Attitudes: A Multispecialty Survey of Residents.

OBJECTIVE: The Accreditation Council for Graduate Medical Education measures surgical residents' experience in the United States by mandating that residents log each procedure in which they have participated. This system is the primary mechanism by which breadth and depth of surgical training are documented, and data are used for program accreditation and by individual program directors to assess resident preparedness. The study objective was to learn from residents across surgical specialties how this system is being used, and whether they believe these data are reliable. DESIGN: Investigators developed and administered a voluntary, 45-item survey. Resident demographic data, program details, logging behaviors, and attitudes were examined using descriptive statistics. Authors used multivariate logistic regression to assess respondent and program characteristics associated with logging habits. SETTING: The survey was administered at a large academic medical center. PARTICIPANTS: All general surgery, obstetrics and gynecology, orthopedics, urology, neurosurgery, otolaryngology, and plastic surgery residents were eligible. Of 126 surgical residents, 82 participated, yielding a response rate of 65%. RESULTS: Overall, 7.5% considered the case log system highly inaccurate, 28.8% somewhat inaccurate, 52.5% somewhat accurate, and 11.3% highly accurate. Nearly half (48.1%) use an incorrect metric to log their role as surgeon or assistant. Half logged monthly or less frequently. The longest time residents reported falling behind ranged from less than a week to more than a year, with about half (51.4%) reporting backlogs of 3 months or longer. Approximately two-thirds considered the system difficult to navigate (64.2%) and burdensome (68.8%). Departmental training and reminders to log were associated with high fidelity logging habits. CONCLUSIONS: Inconsistency of logging habits and perceived lack of accuracy raise concerns about use of the system for assessing surgical preparedness or accrediting training programs. Academic departments playing an active role may benefit from more reliable data to guide improvements in surgical training.

The effect of age and medical comorbidities on in vitro myoblast expansion in women with and without pelvic organ prolapse.

INTRODUCTION: This is an observational study is designed to assess the influence of age, prolapse and medical co-morbidities on myogenic stem cells growth in-vitro. METHODS: A biopsy of the rectus abdominus muscle was obtained during surgery in patients with and without pelvic organ prolapse (POP). Nuclei number and fiber count were correlated with patient's age, presence of POP, and medical comorbidities. Efficiency of expansion of myogenic stem cells in vitro was calculated. The percentage of Pax7-, MyoD-, and desmin-positive cells was correlated with age, POP status, and medical comorbidities. RESULTS: A total of 17 specimens were obtained; 13 specimens were available for histologic analysis. There was no correlation between patient's age, POP status or medical comorbidities and nuclei or fiber count, growth rate, or the percentage of Pax7- and MyoD-positive cells. Patients with 2 to 4 medical comorbidities were noted to have a significantly lower percentage of desmin-positive cells. Specimens with a higher nuclear count had significantly better cellular expansion. Data were analyzed using Kruskal-Wallis or Wilcoxon rank sum statistics. CONCLUSIONS: Multiple medical comorbidities but not patient's age or POP status influenced in vitro myogenic stem cell growth. These data suggest that patients with advancing age or POP may be acceptable autologous donors if treatment of urinary or anal incontinence requires myoblast transplantation.

Safety assessment of myogenic stem cell transplantation and resulting tumor formation.

OBJECTIVES: To assess for stem cell migration to liver and lung after transplantation in injured rat anal sphincters. To evaluate histological findings of unanticipated ectopic foci of growth. METHODS: This is a prospective study involving 33 female virginal Sprague-Dawley rats. Anal sphincters were transected and repaired under sterile technique. Animals received injections of 5.0 × 10 myogenic stem cells (24 rats) or sham control (9 rats) and were killed on day 30. Liver and lung samples were obtained. Upon encountering abnormal foci of growth, further staining protocols were employed. Enzyme-linked immunosorbent assay studies evaluated stem cell media for in vitro growth factor secretion. RESULTS: No evidence of cell migration to liver or lung was found at the time of euthanasia in any study animal. Ectopic foci of growth were noted in 2 transplant rats. Further histological evaluations of these growths were consistent with benign tumors: no nuclear abnormalities and no evidence of proliferation at day 30. Enzyme-linked immunosorbent assay studies demonstrated positive secretion of vascular endothelial growth factor and insulin growth factor into the media of cultured rat myogenic stem cells. CONCLUSIONS: Whereas distant migration was not encountered in the liver or lung, 2 transplanted rats developed abnormal foci of growth, that is, tumors, from the external anal sphincter-raising further safety questions. Additional evaluation of these foci seemed benign. Possible explanations include cell trapping, stem cell overgrowth, and/or paracrine factors. The lack of cell migration supports that future investigation of safety parameters could focus locally.

Use of composite grafts in abdominal sacrocolpopexy.

OBJECTIVE: : The ideal graft material for pelvic reconstructive surgery remains undetermined. The purpose of this study was to present data on novel composite biologic/synthetic grafts during use in abdominal sacrocolpopexy. METHODS: : A case series of 90 patients undergoing abdominal sacrocolpopexy with composite biologic/synthetic grafts was conducted. The primary outcome was graft erosion. Assuming a 3% risk of reoperation for mesh erosion, the number needed to treat with a composite graft in order to avoid erosion risk from a synthetic-only graft was calculated. The cost of a composite graft was compared to reoperation costs for mesh erosion of a synthetic-only graft. RESULTS: : Zero patients (N = 90) undergoing abdominal sacrocolpopexy with a composite biologic/synthetic graft experienced graft erosion. Based on existing data, thirty-three patients would need to be treated with a composite graft to avoid one mesh erosion from a synthetic-only graft. If a $500 composite graft is used, the cost of reoperation performed abdominally is higher. CONCLUSIONS: : This study introduces a novel biologic/synthetic composite graft that offers the advantage of low erosion risk during use in abdominal sacrocolpopexy. Combined grafts may also be cost-effective. Future research should focus on exploring the role of these durable, yet low erosion risk grafts to potentially promote improved safety for our patients and cost savings for society.

Allogenic myoblast transplantation in the rat anal sphincter.

OBJECTIVES: : To determine the feasibility of injecting rat myoblasts into the intact anal sphincter as a potential treatment for anal incontinence, and to detect transferred myoblast survival and integration. STUDY DESIGN: : A pilot study using nonpregnant female Sprague Dawley rodents of 8 to 10 weeks of age. A biopsy of skeletal muscle was harvested from a study animal and recovered myoblasts were expanded in vitro over 10 days. Myoblasts were then tagged with a cytomegalovirus promoter to transduce green fluorescent protein (GFP) into the myoblasts. The cell aspirate was injected directly into the intact external anal sphincter using an electromyographic guidance. The animals received 1.5 or 4.5 × 10 cells of GFP-labeled myoblasts, dividing the dose between three injection sites. The remaining in vitro myoblasts were still viable 28 days post-harvest. Ten days after transplantation the anal sphincter complex was surgically extracted. RESULTS: : The presence of GFP-labeled myoblasts was confirmed within the external anal sphincter. CONCLUSIONS: : This demonstrates that myoblasts can be successfully extracted, cultivated in vitro, transplanted and will integrate into the host tissue.

Lynx midurethral sling system: a 1-year prospective study on efficacy and safety.

The objective of this study is to determine the outcomes for the Lynx midurethral sling system in the treatment of urodynamic stress incontinence (USI). Prospective study of 118 subjects who underwent a Lynx midurethral sling procedure for USI. Subjects were considered cured if they were subjectively dry by history and objectively dry by standing stress test. Intraoperative and postoperative complications were documented. Complete information was available on 102 (86%) subjects at 1 year. Ninety-two patients were considered cured, and ten were failures. There were four intraoperative bladder perforations and five (4.2%) erosions. Two patients developed urinary retention with one resolving at 31 days and the other undergoing subsequent takedown at 6 months. Both remain dry at 12 months. The Lynx midurethral sling system shows high subjective and objective success rates for the treatment of USI at 1 year with low rates of intraoperative and postoperative complications.

Does pelvic organ prolapse quantification exam predict urethral mobility in stages 0 and I prolapse?

OBJECTIVE: To determine if women with anterior support stages 0 or I by pelvic organ prolapse quantification (POP-Q) system require Q-tip testing to assess urethral mobility. METHODS: A prospective study of 134 women presenting for urogynecologic evaluation were examined and assigned stages of anterior wall support according to the POP-Q system. A Q-tip test was performed and urethral hypermobility was defined as a straining angle > or =30 degrees. The Spearman correlation coefficient was used to assess degree of correlation between POP-Q point Aa position and Q-tip values. RESULTS: The correlation coefficient between point Aa position and Q-tip angle was r = 0.787 (P < 0.001). Urethral hypermobility was noted in 91% of stage I and 100% of stage II-IV patients. The positive predictive value of Q-tip angle > or =30 degrees in stage I-IV prolapse was 99%. CONCLUSION: The POP-Q system is highly predictive of straining urethral angle in all stages of prolapse.