Urethral Bulking.

OBJECTIVE: This Clinical Practice Statement aims to provide clinicians with evidence-based guidance for the use of urethral bulking agents (UBAs) in the treatment of stress urinary incontinence (SUI). METHODS: We conducted a structured search of the English literature published from January 1960 to November 2022. Search terms identified studies of both current and historic UBAs. Data extracted at the time of full-text review included type of study, research setting, number of participants, age group, bulking agent, primary outcome, secondary outcome, efficacy, and complications. RESULTS: One thousand five hundred ninety-four nonduplicate articles were identified using the search criteria. After limiting the article types to randomized control led trials, prospective studies, guideline documents, reviews, meta-analyses, and case reports of complications, 395 studies were screened. CONCLUSIONS: Based on our findings, we propose the following recommendations for clinicians when considering UBA: First, UBA is indicated in cases of demonstrable SUI. Intrinsic sphincter deficiency is not predictive of patient outcomes. Second, patients should be counseled on the risks, lack of long-term efficacy data, potential need for repeat injections, possible need for surgery for recurrent SUI, implications for future procedures, and pelvic imaging findings that may be observed after UBA. Third, UBA may be considered for initial management of SUI. Fourth, UBA is an option for patients with persistent or recurrent SUI after a sling procedure. Fifth, clinicians may prioritize UBA over surgery in specific patient populations. Sixth, polyacrylamide hydrogel demonstrates marginally improved safety and durability data over other available agents.

Sacrospinous Ligament Fixation Using an Anchor Versus Suture-Capturing Device: A Prospective Cohort Study.

OBJECTIVE: The aim of the study was to compare rates of persistent gluteal and posterior thigh pain, procedural efficacy, and postoperative complications at 1 year after sacrospinous ligament fixation using either an anchor-based or suture-capturing device. METHODS: This prospective cohort study evaluated outcomes 1 year after operation in patients previously enrolled in a randomized controlled trial comparing an anchor-based versus suture-capturing device for sacrospinous fixation. Symptom scores were evaluated via Pelvic Floor Distress Inventory 20 and Pelvic Floor Impact Questionnaire 7. Pain was evaluated using the Numerical Rating Scale. Composite surgical failure was defined as prolapse beyond the hymen or C-point greater than one half down the vagina, vaginal bulge symptoms, or a need for prolapse retreatment via surgery or pessary management. Descriptive and bivariate statistics were performed. RESULTS: Forty three (21 anchors, 22 sutures) of the original 47 patients (91%) returned for follow-up. The mean follow-up time was 15.4 months, age was 69 years old, body mass index was 30, and preoperative Pelvic Organ Prolapse Quantification stage was 2.7. No patients reported significant increase in pain at sacrospinous fixation site above baseline, and there was no significant difference in posterior thigh or gluteal pain on the side of fixation compared with baseline in the anchor-based or suture-capture groups (-0.2 ± 0.9 and -0.5 ± 1.6, respectively, P = 0.719). Two patients demonstrated surgical failure (anchor group) due to bulge symptoms (P = 0.233). The devices similarly improved Pelvic Floor Distress Inventory 20 (-71.0 ± 45.5 vs -66.3 ± 64.4, P = 0.652) and Pelvic Floor Impact Questionnaire 7 (-40.6 ± 62.4 vs -26.4 ± 65.7, P = 0.768) scores. CONCLUSIONS: Persistent gluteal or posterior thigh pain and surgical failure is uncommon 12 months after sacrospinous fixation and was not associated with the type of fixation device.

Gluteal and Posterior Thigh Pain From a Suture Compared With an Anchor-Based Device in Patients Undergoing Sacrospinous Ligament Fixation: A Randomized Controlled Trial.

OBJECTIVE: To compare postoperative gluteal and posterior thigh pain, device performance, and perioperative complications in women undergoing sacrospinous ligament fixation with an anchor-based compared with a suture-capturing device. METHODS: This was a single-center, patient-blinded, parallel, superiority trial of patients undergoing native-tissue pelvic organ prolapse repair through sacrospinous ligament fixation with an anchor-based compared with suture-capturing device using randomized-block randomization. The primary outcome was the increase in gluteal and posterior thigh pain from baseline to 1-week postoperation using the numerical rating scale. Pain was also assessed at postoperative day 1, week 6, and a summarized assessment for the first postoperative week. Intraoperative device performance, home opioid pain medication use, and changes in prolapse symptom scores were also analyzed. To provide 80% power to detect a pain difference of 2.5 points between the groups with an SD of 2.8 and a 15% dropout estimate using a two-sided 5% significance level, 24 patients were required per group. Analysis with Student's t test, Wilcoxon rank-sum tests, and Fisher exact tests were performed as well as an analysis of covariance for the primary outcome. RESULTS: Between September 2018 and June 2020, 47 patients (24 anchor-based and 23 suture-capturing) were included in the study. There was no significant difference between the anchor-based and suture-capture groups in mean change in gluteal and posterior thigh pain from baseline to 1-week postoperation (-0.4, 95% CI -1.6 to 2.3). The highest pain increase from baseline during the first postoperative week was also similar between the two groups (up 4.00 and up 4.74, respectively) with no significant difference between the anchor-based and suture-capture groups (-0.7, 95% CI -1.4 to 2.8). There were no differences in changes in pain at any of the other timepoints, in opioid pain medication utilization, device performance, or in prolapse symptom scores. CONCLUSION: An anchor-based device did not reduce postoperative gluteal and posterior thigh pain compared with a suture-based device after sacrospinous ligament fixation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03565640. FUNDING SOURCE: Supported by Neomedic via Adler Instruments. Neomedic provided funding for this principal investigator-initiated study. Funding went to providing small value gift cards to patients for study completion, office supplies for the study, and funding the data analysis collaboration with the Wake Forest Baptist Health CTSI Biostatistics Department. Neomedic did not have any direct role in study design, patient recruitment, study execution, data analysis, or manuscript writing or editing.

Anesthetic Bladder Capacity is a Clinical Biomarker for Interstitial Cystitis/Bladder Pain Syndrome Subtypes.

OBJECTIVE: To further examine anesthetic bladder capacity as a biomarker for interstitial cystitis/bladder pain syndrome (IC/BPS) patient subtypes, we evaluated demographic and clinical characteristics in a large and heterogeneous female patient cohort. MATERIAL AND METHODS: This is a retrospective review of data from women (n = 257) diagnosed with IC/BPS who were undergoing therapeutic bladder hydrodistention (HOD). Assessments included medical history and physical examination, validated questionnaire scores, and anesthetic BC. Linear regression analyses were computed to model the relationship between anesthetic BC and patient demographic data, symptoms, and diagnoses. Variables exhibiting suggestive correlations (P ≤ .1) were candidates for a multiple linear regression analysis and were retained if significant (P ≤ .05). RESULTS: Multiple regression analysis identified a positive correlation between BC and endometriosis (P = .028) as well as negative correlations between BC and both ICSI score (P < .001) and the presence of Hunner's lesions (P < .001). There were higher average numbers of pelvic pain syndrome (PPS) diagnoses (P = .006) and neurologic, autoimmune, or systemic pain (NASP) diagnoses (P = .003) in IC/BPS patients with a non-low BC, but no statistical difference in the duration of diagnosis between patients with low and non-low BC (P = .118). CONCLUSION: These data, generated from a large IC/BPS patient cohort, provide additional evidence that higher BC correlates with higher numbers of non-bladder-centric syndromes while lower BC correlates more closely with bladder-specific pathology. Taken together, the results support the concept of clinical subgroups in IC/BPS.

Short-term outcomes of sacrospinous hysteropexy through an anterior approach.

INTRODUCTION AND HYPOTHESIS: The posterior approach to sacrospinous hysteropexy has been well studied but little is known about the anterior approach. This study assessed the efficacy and complications of an anterior approach to sacrospinous hysteropexy compared to hysterectomy with apical repair. We hypothesized that anterior sacrospinous hysteropexy has similar efficacy and fewer complications. METHODS: This retrospective cohort study compared patients who underwent native-tissue anterior sacrospinous hysteropexy (cases) with those who underwent hysterectomy with apical repair (controls). Composite success was defined as (1) leading edge of prolapse not beyond the hymen and apex not descended > 1/3 total vaginal length; (2) no vaginal bulge symptoms; (3) no prolapse retreatment. Descriptive and bivariate statistics were performed as well as a Cox regression analysis for time to failure. RESULTS: Fifty cases and 97 controls were compared. The median follow-up time was 7.6 months. Operative time was shorter in the hysteropexy group (110.7 vs. 155.9 min, p < 0.001). The composite success was 92% for both cases and controls (p = 1.000) with no difference in time to surgical failure (p = 0.183). There were no serious intraoperative complications in the hysteropexy group and six in the control group (3 transfusions, 1 conversion to laparotomy, 1 ureteral injury, 1 cystotomy; p = 0.101). There was no difference in the number of postoperative complications (22.0% vs. 30.9%, p = 0.203). CONCLUSIONS: For primary uterine prolapse, anterior sacrospinous hysteropexy has similar short-term efficacy compared to hysterectomy with apical repair with shorter operative time and a trend towards fewer serious complications.

Native tissue sacrospinous hysteropexy from an anterior approach.

AIM OF THE VIDEO: The goal of urogynecologic surgeons is to pair patients with the most appropriate and effective surgery. Sacrospinous hysteropexy has become an increasingly utilized surgical option for uterovaginal prolapse repair. The primary aim of this video is to highlight the role that sacrospinous hysteropexy can have in prolapse repair and to demonstrate an anterior approach for this procedure. METHODS: We performed a literature review to provide general information on the efficacy, risks, and comparative benefits of sacrospinous hysteropexy. Our video demonstrates the key steps in performing a sacrospinous hysteropexy procedure from an anterior approach including method of dissection, suture fixation to the sacrospinous ligament, and cervical suspension. RESULTS: Sacrospinous hysteropexy has generally been found to be an effective option for uterovaginal prolapse repair in properly selected patients. The demonstrated approach integrates sacrospinous ligament fixation with an anterior colporrhaphy. CONCLUSIONS: Data and experience to date on sacrospinous hysteropexy are largely based on a posterior approach for access to the sacrospinous ligament. This surgical video demonstrates an anterior approach to sacrospinous hysteropexy that is not well characterized in the literature.

Regenerative medicine for anal incontinence: a review of regenerative therapies beyond cells.

INTRODUCTION AND HYPOTHESIS: Current treatment modalities for anal sphincter injuries are ineffective for many patients, prompting research into restorative and regenerative therapies. Although cellular therapy with stem cells and progenitor cells show promise in animal models with short-term improvement, there are additional regenerative approaches that can augment or replace cellular therapies for anal sphincter injuries. The purpose of this article is to review the current knowledge of cellular therapies for anal sphincter injuries and discusses the use of other regenerative therapies including cytokine therapy with CXCL12. METHODS: A literature search was performed to search for articles on cellular therapy and cytokine therapy for anal sphincter injuries and anal incontinence. RESULTS: The article search identified 337 articles from which 33 articles were included. An additional 12 referenced articles were included as well as 23 articles providing background information. Cellular therapy has shown positive results for treating anal sphincter injuries and anal incontinence in vitro and in one clinical trial. However, cellular therapy has disadvantages such as the source and processing of stem cells and progenitor cells. CXCL12 does not have such issues while showing promising in vitro results for treating anal sphincter injuries. Additionally, electrical stimulation and extracorporeal shock wave therapy are potential regenerative medicine adjuncts for anal sphincter injuries. A vision for future research and clinical applications of regenerative medicine for anal sphincter deficiencies is provided. CONCLUSION: There are viable regenerative medicine therapies for anal sphincter injuries beyond cellular therapy. CXCL12 shows promise as a focus of therapeutic research in this field.

Optimal timing of a second postoperative voiding trial in women with incomplete bladder emptying after vaginal reconstructive surgery: a randomized trial.

BACKGROUND: Rates of postoperative incomplete bladder emptying vary significantly after pelvic reconstructive surgery. With enhanced recovery protocols the paradigm is shifting towards same-day discharge and the rates of incomplete bladder emptying are expected to increase. The optimal length of time for postoperative catheter drainage has not been clearly established. There are no current studies that assess the optimal timing of a repeat voiding trial in women who have unsuccessful same day voiding trials. OBJECTIVE: This study aimed to compare the outcomes of a second voiding trial performed 2-4 days (earlier group) vs 7 days (later group) postoperatively in women with incomplete bladder emptying after vaginal prolapse surgery. Secondary aims included postoperative urinary tract infection rates, total days with a catheter, and patient-reported catheter bother between groups. STUDY DESIGN: Across 2 sites, women undergoing multicompartment vaginal repair were enrolled. Within 6 hours postoperatively, subjects had an active retrograde voiding trial. Those who passed this voiding trial exited the study; those who had persistent incomplete bladder emptying (postvoid residual >100 mL) had a transurethral indwelling catheter placed and were randomized to return for an earlier (postoperative day 2-4) vs later (postoperative day 7) follow-up office voiding trial. Subjects were followed for 6 weeks after surgery. The primary outcome was the rate of unsuccessful repeat office voiding trial. Secondary outcomes included rates of urinary tract infection, total days with a catheter, and subjective catheter bother. A power calculation based on a projected 31% difference, a power of 0.8, and an alpha of 0.05 revealed that 30 subjects were needed in each group. RESULTS: A total of 102 subjects were enrolled; 38 exited on postoperative day 0, leaving 64 subjects for randomization (4 of whom withdrew after randomization). A comparison of data revealed that randomization was effective, with no differences between the earlier and later groups in terms of demographic data or surgical procedures. Using an intention-to-treat analysis, women in the earlier group were more likely to be unsuccessful in their follow-up office voiding trial (23.3%) than the later group (3.3%), with a risk difference of 20% (95% confidence interval, 3.56-36.44) and a relative risk of 7.00 (95% confidence interval, 0.92-53.47; P=.02). A number-needed-to-treat calculation found that for every 5 patients using a catheter for 7 days postoperatively, 1 case of persistent postoperative incomplete bladder emptying was prevented. Rates of catheter bother did not differ between groups at the time of the follow-up office voiding trial or at 6 weeks (P=.09 and P=.20, respectively). Urinary tract infection rates were higher in the earlier group but did not reach statistical significance (23% vs 7%, P=.07). Regression analysis revealed that subjects who required additional pain medication refills were 9.6 times (95% confidence interval, 1.24-73.77) more likely to have persistent incomplete bladder emptying after the follow-up office voiding trial. CONCLUSION: Women with incomplete bladder emptying after multicompartment prolapse repair had a 7-fold higher risk of an unsuccessful repeat office voiding trial if performed within 4 days of surgery than when performed within 7 days of surgery. In addition, requiring additional prescriptions for analgesia increased the risk of an unsuccessful follow-up office voiding trial.

Bladder Hydrodistention Does Not Result in a Significant Change in Bladder Capacity for Interstitial Cystitis/Bladder Pain Syndrome Patients.

OBJECTIVE: To assess the impact of multiple (2 or more) bladder hydrodistentions (HODs) on anesthetic bladder capacity (BC) in a large cohort of interstitial cystitis/bladder pain syndrome (IC/BPS) patients. Urinary HOD under anesthesia is a third line therapeutic approach used to treat patients with IC/BPS. There is some concern that performing multiple therapeutic HODs may be contraindicated due to the potential for contributing to a diminished BC over time. MATERIALS AND METHODS: This is a retrospective chart review of IC/BPS patients from a single institution who had undergone 2 or more bladder HOD procedures. Patient demographic and clinical data, including BC under anesthesia, were retrieved from patient charts for analysis. Least squares regression slopes of BC under anesthesia were calculated and used to estimate within-patient BC changes over time. RESULTS: Data from 168 patients (637 HOD procedures) were included for analysis. The average change in BC, 0.52 ± 8.33 mL/mo, was not significantly different from 0 (P= .42). Linear regression analyses did not identify any significant correlation between BC over time with: (1) age, (2) number of HODs, (3) frequency of HODs, (4) average BC, (5) length of time with an IC/BPS diagnosis, or (6) length of time during which the patient's BC was evaluated. Moreover, there was no difference in BC change over time in patients with and without Hunner's lesion (P = .86). CONCLUSION: Multiple therapeutic HODs, over several years, do not result in a significant change in BC in IC/BPS patients.

X4 human immunodeficiency virus type 1 gp120 down-modulates expression and immunogenicity of codelivered antigens.

In order to increase the immune breadth of human immunodeficiency virus (HIV) vaccines, strategies such as immunization with several HIV antigens or centralized immunogens have been examined. HIV-1 gp120 protein is a major immunogen of HIV and has been routinely considered for inclusion in both present and future AIDS vaccines. However, recent studies proposed that gp120 interferes with the generation of immune response to codelivered antigens. Here, we investigate whether coimmunization with plasmid-encoded gp120 alters the immune response to other coadministered plasmid encoded antigens such as luciferase or ovalbumin in a mouse model. We found that the presence of gp120 leads to a significant reduction in the expression level of the codelivered antigen in vivo. Antigen presentation by antigen-presenting cells was also reduced and resulted in the induction of weak antigen-specific cellular and humoral immune responses. Importantly, gp120-mediated immune interference was observed after administration of the plasmids at the same or at distinct locations. To characterize the region in gp120 mediating these effects, we used plasmid constructs encoding gp120 that lacks the V1V2 loops (DeltaV1V2) or the V3 loop (DeltaV3). After immunization, the DeltaV1V2, but not the DeltaV3 construct, was able to reduce antigen expression, antigen presentation, and subsequently the immunogenicity of the codelivered antigen. The V3 loop dependence of this phenomenon seems to be limited to V3 loops known to interact with the CXCR4 molecule but not with CCR5. Our study presents a novel mechanism by which HIV-1 gp120 interferes with the immune response against coadministered antigen in a polyvalent vaccine preparation.