Faculty Bibliography

Objective: To compare the safety and efficacy of a dermal bovine tissue transvaginal graft, XenformTM (TVG), to traditional native tissue repair (NTR) in women surgically treated for anterior and/or apical pelvic organ prolapse (POP) Methods: This was a prospective, non-randomized, parallel cohort, a multicenter trial where subjects received TVG or NTR. The primary endpoint of the study was to achieve non-inferiority (NI) of transvaginal repair with TVG to NTR at 36 months compared to baseline. Treatment success was based on a composite of objective (leading edge of prolapse at or above the hymen; no POP re-treatment) and subjective (no symptoms of vaginal bulging) outcomes measured at 12, 24, and 36 months. The non-inferiority margin was set at 12%. A propensity score stratification method was applied to achieve balance inpatient and surgeon characteristics between treatment groups. A co-primary outcome was the rate of serious device or serious procedurerelated adverse events (SAE) within 36 months. Secondary endpoints included evaluation of graft-and procedure-related complications between baseline and 36 months Results: The primary outcome, treatment success at 36 months, was 83.6% in TVG and 80.5% in NTR, demonstrating NI (0.2%, 90%CI[-5.6%, 5.9%]) (Table 1). Composite and objective success in apical compartment rate minimally declined with time in both groups (Figure1). The overall rate of SAEs was 5.3% (12/228) vs 2.7% (13/485) in the TVG vs NTR groups, respectively, and TVG was NI to NTR at the preset margin of 12% (2.0%, 90% CI[-0.8%, 4.7%]). Overall AE rates were similar between the TVG and NTR arms: 46.5% (106/228) in TVG subjects and 46.4% (225/485) in NTR subjects. The majority of AEs occurred within the first 6 months following surgery, 77.4% (82/106) for TVG subjects and 67.1% (151/225) for NTR subjects with the most frequently reported AE being de novo voiding dysfunction. There were no reports of graft erosion, and graft exposure rates were low (0.9% [2/228]).
Conclusion(s): Biologic TVG for the treatment of anterior and/or apical vaginal prolapse was as effective as NTR and as safe as NTR with respect to the rate of the serious device-and/or serious procedure-related AEs at 36 months

Objectives: Studies indicate variations exist in surgical route and outcomes for treatment of gynecologic conditions among different races. The aim of this study was to investigate the difference in route of pelvic organ prolapse (POP) surgery and subsequent complications among women of different races and ethnicity in the United States.
Material(s) and Method(s): Data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) was used to estimate surgical route and complication rates. A total of 48,712 patients underwent a POP repair between 2014 and 2018, based on CPT codes. Based on the NSQIP database, patients were grouped by race and Hispanic ethnicity, and the route of POP repair was assessed. Primary outcome was the difference in surgical route (vaginal, laparoscopic, and abdominal) between groups. Secondary outcomes were differences in concomitant procedures and post-operative complications between groups. Descriptive statistics were used to analyze the data. All confidence intervals were computed using the normal approximation method. Statistical significance was P < 0.05.
Result(s): While a vaginal approach was the most common route across all groups, there was a significant difference in the route of POP repair among women of different races and ethnicities (P < 0.001; Table 1). Analysis revealed significantly more Black women undergoing laparoscopic procedures (P < 0.001), and more Hispanic women undergoing an abdominal approach (P < 0.001) than other groups. Black, Asian, and Hispanic women were more likely to undergo a hysterectomy than White women at the time of POP repair (P < 0.001). Black women were less likely to receive a concomitant sling than all other groups (P < 0.001). While readmission rates were not statistically different (P = 0.06; Table 2), the occurrence of one or more adverse event was significantly different between races (P < 0.0001), as was reoperation rate (P = 0.04). Black and Hispanic women were transfused 2-fold more often than White women, although the rates of transfusion overlapped with other non-White races (P < 0.001).
Conclusion(s): Surgical approach to and outcomes of POP surgery differed significantly between races and Hispanic ethnicity. While more is needed to assess the impact of pre-existing co-morbidities on routes of surgery, reasons for why differences exist may not be fully elucidated from this dataset. Findings may reflect variations in prevalence of concurrent disorders among racial/ethnic groups, provider biases, patient preferences, and access to subspecialty-trained surgeons. [Formula presented] [Formula presented]
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CONTEXT/BACKGROUND:The role of overactive bladder (OAB) treatment in women beyond antimuscarinics has been evaluated extensively. Beta-3 agonists, botulinum toxin-A (BTX-A), and nerve stimulation are indicated in these patients. However, data on male patients in this clinical scenario are scarce. OBJECTIVE:The aim of this systematic review was to evaluate the evidence on treatment options beyond antimuscarinics in men with OAB. EVIDENCE ACQUISITION/METHODS:A search of PubMed, EMBASE, Scopus, Web of science, Cochrane Central Register of Controlled Trials, and Cochrane Central Database of Systematic Reviews databases was performed for relevant articles published between January 2000 and October 2020, using the following Medical Subject Headings: "male/man," "LUTS," "overactive bladder," "storage symptoms," "urgency," "nocturia," "incontinence," "beta-3 agonist," "PDE-5 inhibitors," "botulinum toxin," "sacral nerve stimulation/neurostimulation," "percutaneous/transcutaneous tibial nerve stimulation," "PTENS," and "combination therapy." Evidence acquisition was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PROSPERO registration number is CRD42020201223. EVIDENCE SYNTHESIS/RESULTS:-blocker tamsulosin improved the mean number of micturitions per day (-0.27, 95% CI: -0.46 to -0.09, p <  0.05), urgency episodes (-0.50, 95% CI: -0.77 to -0.22, p <  0.05), total OAB symptom score (-0.66, 95% CI: -1.00 to -0.38, p <  0.05), and mean volume voided (+10.76 ml, 95% CI: 4.87-16.64, p <  0.05). MIRA treatment is well tolerated in men. Other pharmacological treatment options, such as phosphodiesterase-5 (PDE-5) inhibitors, should be considered investigational. BTX-A seems to be effective as third-line treatment in male OAB patients. A higher rate of intermittent self-catheterization (5-42%) is observed in male than in female patients. Data on nerve stimulation are scarce. CONCLUSIONS:MIRA has the most robust data in terms of safety and efficacy in this patient population. Preliminary data in men suggest that BTX-A is indicated as an interventional treatment. Evidence for PDE-5 inhibitors and nerve stimulation is too limited to provide recommendations. Future studies in this population should aim to better define the best treatment sequence and to identify predictors for treatment response and failure, to determine a therapeutic approach tailored to patients' characteristics. PATIENT SUMMARY/UNASSIGNED:Overactive bladder is highly prevalent in men. Mirabegron 50 mg is the treatment option supported by the highest level of evidence when antimuscarinics failed. Botulinum toxin A injections seems to be an effective treatment as interventional option. Roles of nerve stimulation and phosphodiesterase inhibitors in male OAB patients are still to be defined.

INTRODUCTION AND HYPOTHESIS/OBJECTIVE:The aim of this study was to assess whether mid-urethral sling (MUS) placement at the time of vaginal prolapse repair compared to vaginal prolapse repair alone is associated with an increase in 30-day postoperative complications. METHODS:Using the American College of Surgeons National Surgical Quality Improvement Database, Current Procedural Terminology codes were used to identify cases of vaginal prolapse repair with and without concomitant MUS from 2012 to 2017. Student's t-test and chi-square test were used to compare differences between the groups. RESULTS:A total of 1469 cases of vaginal prolapse repair with sling were compared to 4566 cases without sling. There was no difference between prolapse repair with sling compared to without sling in mean hospital length of stay (LOS) (1.42 versus 1.32 days, p = 0.65), postoperative urinary tract infection (UTI) (6.1% versus 5.8%, p = 0.670), perioperative blood transfusion (1.1% versus 1.2%, p = 0.673), readmission (2.7% versus 2.6%, p = 0.884) and postoperative wound infection (0.5% versus 0.7%, p = 0.51). There was a higher rate of reoperation (2.2% versus 1.5%, p = 0.049) and venous thromboembolism (VTE) (0.4% versus 0.1%, p = 0.030) in patients undergoing concomitant MUS compared to those undergoing prolapse repair alone. CONCLUSIONS:Compared to prolapse repair alone, the addition of a sling did not increase hospital LOS, UTI, perioperative blood transfusions, readmission or postoperative wound infections. However, concomitant sling was found to be associated with a higher risk of reoperation and VTE.

OBJECTIVES/OBJECTIVE:To evaluate whether progression to maintenance percutaneous tibial nerve stimulation (PTNS) was related to perceived global impression of improvement (PGII) rather than symptom-specific improvement in patient with overactive bladder (OAB). We hypothesize that PGII will predict continuation of PTNS long-term. METHODS:This prospective observational study included 90 patients with OAB that initiated PTNS. The PGII and overactive bladder short-form questionnaires (OABq-SF) were used to assess bladder symptom severity and improvement. Those that completed the 12-week induction phase were offered to continue PTNS monthly maintenance or pursue other options. The primary outcome was difference in PGII score between those pursuing maintenance therapy versus other options. Descriptive statistics and mixed effect modeling analysis were employed. RESULTS:Seventy patients (78%) completed 12 weeks of PTNS. The majority of completers pursued monthly maintenance (p<0.01) and had significantly lower median PGII scores compared with those who sought alternatives (p<0.01), while OABq-SF scores did not differ significantly (p=0.65). Patients that pursued monthly PTNS maintenance had lower body mass index than those who chose alternative therapies (p<0.01). Only 19% continued PTNS therapy for at least 1 year. CONCLUSIONS:More patients pursued PTNS monthly maintenance over any other therapy, and this was significantly associated with lower PGII scores. Global improvement, and not symptom-specific response, predicts long-term PTNS maintenance. No symptom-specific predictors were identified in those who pursued maintenance over other options. One-year continuation rates are low.

Introduction: Urodynamics (UDS) is the study of urine transport, storage, and evacuation and is the gold standard in assessment of bladder function. Per AUA guidelines, UDS are not to be used in the initial workup of the uncomplicated patient with OAB, however their role in more complex patients remains uncertain. The primary aim of this study is to assess the impact of UDS on diagnosis and treatment plans of complex patients with OAB.
Method(s): Patients undergoing workup for OAB between 2016 and 2018 were prospectively enrolled and completed a voiding diary and UDS. Physicians first provided a diagnosis and treatment plan based on patient history, clinical data and voiding diary alone. The patients then underwent UDS and the physician provided a diagnosis and treatment plan after reviewing the additional testing. The impact of UDS on diagnosis and treatment plan were analyzed.
Result(s): 26 patients underwent evaluation with voiding diary and UDS with prospective documentation of diagnosis and treatment plan. All patients had previously trialed oral OAB medications10 (38.4%), complained of mixed incontinence 11 (42.3%), or were considering third line therapy 14 (53.8%). After UDS were performed, 13 (50%) had a modification in diagnosis and 11 (42.3%) had a change in treatment plan. The most common change in diagnosis was observation of voiding phase dysfunction in 4 (15.4%). Treatment plans changed for 6 patients with mixed incontinence primarily by elucidating severity of stress vs urgency incontinence when it was difficult to determine from patient report and available clinical data. Plans also changed for 1 patient found to have underactive bladder and 2 with bladder outlet obstruction. 9 (34.6%) patients went on to third line therapy.
Conclusion(s): UDS done for patients with complex OAB symptoms led to modification in patient diagnosis in 50% of patients and change in treatment plan in 42.3%. Change to diagnosis and management plan may reflect the utility of UDS especially in complicated patients (ie mixed incontinence) or who have failed second line therapies

Introduction: Overactive bladder (OAB) affects 10-19% of adults, strongly influencing quality of life. Voiding diaries may provide valuable information on the OAB patient, identifying modifiable behavior factors and the timing and severity of symptoms that can help guide treatment. The primary aim of this prospective cohort study is to report the percent of patients completing a diary, and secondary aim is to assess what factors may predict completion.
Method(s): 93 patients undergoing workup for OAB between 2016 and 2020 were enrolled and asked to complete a three-day voiding diary. They were provided standard written and oral instructions, in addition to urine collection device and a printed diary template. Completed voiding diary, OAB-q questionnaire, and demographic factors were collected and analyzed.
Result(s): Of the 93 patients enrolled, 61 (65.6%) completed at least one day of a voiding diary. Two of these patients (3.3%) returned diaries that could not be interpreted. There was no difference in OAB-q score for those completing diary and those who did not (76.7 vs 79, p=0.86). In addition, no significant differences were seen in age, BMI, ethnicity, gender or prior surgeries between those who did and did not complete the diary.
Conclusion(s): Voiding diaries are used in the workup of OAB to quantify symptoms and determine their cause. We found a completion rate of 65.6% among patients with bothersome OAB. No demographic differences were observed between those who did and did not complete a diary. Further study of barriers to completion could aid in higher capture rates and improved diagnostic evaluation of the OAB patient

Introduction: The introduction of beta3-adrenergic receptor (AR) agonists has improved management of overactive bladder (OAB) by providing efficacious treatment of symptoms while minimizing adverse events associated with anticholinergics. However, beta-ARs are also found outside the bladder (eg, beta1-ARs on cardiomyocytes), which could lead to off-target activity. Results in humans indicate that mirabegron, a beta3-AR agonist approved for the treatment of OAB, stimulates beta1-ARs at a supratherapeutic dose. Further, onset of action of mirabegron 25 mg may take up to 8 weeks, potentially necessitating dose titration upward. Vibegron is a novel, selective beta3-AR agonist with a rapid, 2-week onset of efficacy at a single dose. Here we assessed the potency and maximal effect of vibegron and mirabegron for beta3-ARs and the selectivity for each beta-AR.
Method(s): Functional cellular assays for vibegron and mirabegron activity were performed using Chinese hamster ovary (CHO) cells expressing beta1-or beta2-ARs and human embryonic kidney (HEK) 293 cells expressing beta3-ARs. Cells were incubated with vibegron, mirabegron, or the appropriate control (isoproterenol for beta1 and beta3, procaterol for beta2). Responses were quantified using homogeneous time-resolved fluorescence of cyclic adenosine monophosphate. Half-maximal effective concentration (EC50) and maximum response (Emax) values were determined by nonlinear least-squares regression analysis.
Result(s): Treatment of HEK293 cells with vibegron or mirabegron resulted in concentration-dependent responses at beta3-ARs (Figure). Mean (SEM) EC50 values at the beta3-AR were 2.13 (0.25) nM for vibegron and 10.0 (0.56) nM for mirabegron. At a concentration of 10 muM, beta3-adrenergic activity relative to isoproterenol was 104% for vibegron and 88% for mirabegron. In CHO cells, beta1-adrenergic activity was 0% and 3% for vibegron and mirabegron, respectively, and beta2-adrenergic activity was 2% and 15%. Emax for vibegron and mirabegron at the beta3-AR was estimated to be 99.2% and 80.4%, respectively.
Conclusion(s): Vibegron showed no measurable beta1 and low beta2 activity compared with mirabegron, which showed measurable beta1 and some beta2 activity. Both vibegron and mirabegron showed significant selectivity at beta3-ARs as expected; however, vibegron demonstrated near-exclusive beta3 activity and was approximately 5 times more potent than mirabegron at activating beta3-ARs. Vibegron also showed higher maximum beta3 response, approximating 100%

AIM/OBJECTIVE:Venous thromboembolism (VTE) rates in vaginal pelvic organ prolapse (POP) repair are low. Our aim is to evaluate specific risk factors for VTE in patients undergoing vaginal POP repair. METHODS: tests for categorical variables. Multivariate logistic regression was performed to identify factors independently associated with VTE. RESULTS:Of 44 207 women who underwent vaginal POP repair, there were 69 cases of VTE (0.16%). VTE rates for obliterative (0.15%) and functional (0.16%) vaginal POP repair, as well as for repairs with hysterectomy (0.17%) and without hysterectomy (0.12%) were not significantly different (p = .616 and .216, respectively). Multivariate analysis demonstrated predictors for postoperative VTE to be ASA physical status classification ≥ 3 (aOR, 1.99; p = .014), length of stay >75th percentile (aOR, 2.01; p = .007), operative time >3 h (aOR, 2.24; p = .007), and dyspnea (aOR, 3.26, p = .004). CONCLUSION/CONCLUSIONS:Despite the low incidence of VTE after vaginal POP repair, patients with ASA physical status classification ≥ 3, length of stay >75th percentile, operative time >3 h, and dyspnea were at higher risk for VTE. Vaginal POP repair may have independent VTE risk factors not captured in standard risk assessment tools.