Thorough QT/QTc study to evaluate the effect of a single supratherapeutic dose of islatravir on QTc interval prolongation in healthy adults.

Islatravir is a deoxynucleoside analog being developed for the treatment of HIV-1 infection. Clinical studies are being conducted to evaluate islatravir, administered in combination with other antiretroviral therapies, at doses of 0.25 mg once daily and 2 mg once weekly. In multiple previous clinical studies, islatravir was generally well tolerated, with no clear trend in cardiac adverse events. A trial was conducted to evaluate the effect of islatravir on cardiac repolarization. A randomized, double-blind, active- and placebo-controlled phase 1 trial was conducted, in which a single dose of islatravir 0.75 mg, islatravir 240 mg (supratherapeutic dose), moxifloxacin 400 mg (active control), or placebo was administered. Continuous 12-lead electrocardiogram monitoring was performed before dosing through 24 hours after dosing. QT interval measurements were collected, and safety and pharmacokinetics were evaluated. Sixty-three participants were enrolled, and 59 completed the study. Fridericia's QT correction for heart rate was inadequate; therefore, a population-specific correction was applied (QTcP). The placebo-corrected change from baseline in QTcP (ΔΔQTcP) interval at the observed geometric mean maximum plasma concentration associated with islatravir 0.75 mg and islatravir 240 mg was <10 ms at all time points. Assay sensitivity was confirmed because the use of moxifloxacin 400 mg led to a ΔΔQTcP >10 ms. The pharmacokinetic profile of islatravir was consistent with that of previous studies, and islatravir was generally well tolerated. Results from the current trial suggest that single doses of islatravir as high as 240 mg do not lead to QTc interval prolongation.

A randomized trial of retropubic vs single-incision sling among patients undergoing vaginal prolapse repair.

BACKGROUND: The choice of midurethral sling type may impact efficacy and complications in women undergoing transvaginal native tissue repair of pelvic organ prolapse. OBJECTIVE: The primary aim was to determine if the single-incision sling is noninferior to retropubic sling for the management of stress urinary incontinence among patients undergoing reconstructive or obliterative native tissue vaginal repair. The secondary aims were to compare adverse events and surgeon ease of use with sling assignment. STUDY DESIGN: A multicenter, noninferiority, randomized trial of women with ≥ stage II pelvic organ prolapse and objectively confirmed stress urinary incontinence undergoing reconstructive or obliterative vaginal repair was performed. Women were randomized to concomitant single-incision (Altis sling, Coloplast Minneapolis, MN) with suprapubic sham incisions or retropubic slings. The primary dichotomous outcome was abnormal lower urinary tract function within 12 months postsurgery, defined as bothersome stress urinary incontinence symptoms (>1 Pelvic Floor Distress Inventory question no. 17); retreatment for stress urinary incontinence or treatment for urinary retention. Secondary outcomes were adverse events, Patient Global Impression of Improvement of bladder function, and surgeon ease of use (1, worst; 10, best). All subjects completed validated questionnaires and underwent a Pelvic Organ Prolapse Quantification, cough stress test, and postvoid residual preoperatively, at 6 weeks and 12 months postoperatively. Assuming a subjective cure rate for retropubic of 82%, 80% power, and 1-sided 5% significance level, we estimated that 127 patients in each arm were needed to declare noninferiority of the single-incision sling if the upper bound of the 95% confidence interval for the between-group difference per protocol in abnormal bladder function was <12%. Assuming a 10% loss to follow-up, the total enrollment goal was 280. RESULTS: Between December 2018 and January 2023, 280 subjects were enrolled across 7 sites, and 255 were randomized: 126 were for single-incision, and 129 were for retropubic sling. There were no preoperative or operative characteristic differences between groups. Overall, 81% had reconstructive, and 19% had obliterative native tissue repairs. The primary outcome, abnormal lower urinary tract function at 12 months, occurred in 29 (25%) of single-incision vs 24 (20%) of the retropubic sling group (risk difference, 0.04472 [95% confidence interval, -0.03 to 0.1133]; P=.001 for noninferiority). Bothersome stress urinary incontinence occurred in 20% vs 17% (P=.27) and was retreated in 4% vs 2% (P=.44) of single-incision vs retropubic groups, respectively. Adverse events were reported in 24 (16%) of single-incision vs 14 (9%) of the retropubic group (95% confidence interval, 0.95-3.29; P=.70) and included de novo or worsening urgency incontinence symptoms, urinary tract infection, mesh exposure, need for prolonged catheter drainage, and de novo pain, without differences between groups. Patient Global Impression of Improvement (very satisfied and satisfied) was 71% vs 67% (P=.43), and median surgeon ease of sling use was 8 (7-10) vs 9 (8-10), P=.03 in single-incision vs retropubic, respectively. CONCLUSION: For women undergoing vaginal repair, single-incision was noninferior to retropubic sling for stress urinary incontinence symptoms, and complications, including treatment for urinary retention, did not differ.

The impact of verbal goal setting on operating room turnover time: a randomized trial.

INTRODUCTION AND HYPOTHESIS: Operating room turnover times are highly variable, with longer times having a significant negative impact on hospital costs, surgeon volume, and satisfaction. The primary aim of this randomized trial was to examine the impact of a verbalized time goal on the likelihood of meeting institutional goals. METHODS: This is a prospective, single-blind, randomized study conducted across four operative sites: inpatient main campus and three outpatient centers. Sequential cases for the same surgeon in the same room were randomized to receive a verbal prompt versus usual care, in which no goal setting was verbalized. Multivariate and univariate statistical analyses were performed. RESULTS: From July through October 2022, five attending surgeons randomized 88 cases (44 verbal prompt, 44 usual care). Of these, 30 were at the main inpatient hospital. The case mixture included 36% vaginal, 27% endoscopy, 8% open, 10% robotic, and others. Average turnover time was 51.7 and 35.3 min for inpatient and outpatient cases respectively. Overall, only 39.8% of cases hit the institutional turnover time goal. Verbal prompting did not significantly increase the likelihood of achieving the institutional goal (38.4% vs 43.4% p = 0.352) except for in minor surgery (64.0 vs 39.0%, p = 0.0477). A verbal prompt reduced turnover time in major surgery (59.7 vs 47.8 min, p = 0.0445). CONCLUSION: Our academic center achieved goal turnover times in only 39.8% of cases. Although verbal prompting did not significantly improve the likelihood of meeting institutional goals in the group as a whole, some subgroups were significantly improved.

Injection site number and outcomes of intradetrusor onabotulinumtoxinA for refractory overactive bladder syndrome: a randomized clinical trial.

INTRODUCTION AND HYPOTHESIS: The optimal number of onabotulinumtoxinA injections for the treatment of refractory overactive bladder syndrome is unknown. Our primary objective was to determine whether 10-injections sites with 100 units of onabotulinumtoxinA each were associated with less pain than 20-injections sites. METHODS: In a single-blinded randomized trial, 100 units of onabotulinumtoxinA was administered, either as 10 × 1 ml or as 20 × 0.5 ml injections following the instillation of 30 ml of bupivacaine and 5 ml of NaHCO3 solution for 15 min. The primary outcome was procedural pain, as measured on an 11-point Numerical Pain Rating Scale (NPRS) immediately following the procedure. A power calculation estimated that 16 subjects in each arm were needed to detect a mean difference of 1 with a standard deviation of 1, on the NPRS score between the two treatment groups, with α 0.05 and power 80%. To adjust for an estimated 20% dropout rate, the final sample size was planned for 20 patients per group. RESULTS: From October 2020 to November 2022, a total of 56 patients were approached and 40 were enrolled and randomized to two groups (21 in the 10-injections group and 19 in 20-injections group). The difference in the median pain score between the group was not statistically significant (4 [1.5-5] for 10 injections vs 3 [1-4] for 20 injections, p=0.823). CONCLUSION: Patients' perception of pain, efficacy, and adverse events did not significantly differ between patients receiving 10 and those receiving 20 injections of 100 units of onabotulinumtoxinA.

Long-Term Mesh Exposure 5 Years Following Minimally Invasive Total Hysterectomy and Sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: The objective was to assess long-term mesh complications following total hysterectomy and sacrocolpopexy. METHODS: In this second extension study, women from a multicenter randomized trial were followed for more than 36 months after surgery. Owing to COVID-19, participants were assessed through either in-person visits or telephone questionnaires. The primary outcome was the incidence of permanent suture or mesh exposure. Secondary outcomes included surgical success and late adverse outcomes. RESULTS: Out of the 200 initially enrolled participants, 82 women took part in this second extension study. Among them, 46 were in the permanent suture group, and 36 in the delayed absorbable group. The mean follow-up duration was 5.3 years, with the cumulative mesh or suture exposure of 9.9%, involving 18 cases, of which 4 were incident cases. Surgical success after more than 5 years stood at 95%, with few experiencing bothersome bulge symptoms or requiring retreatment. No serious adverse events occurred, including mesh erosion into the bladder or bowel. The most common adverse events were vaginal pain, bleeding, dyspareunia, and stress urinary incontinence, with no significant differences between suture types. CONCLUSION: The study found that mesh exposure risk gradually increased over time, reaching nearly 10% after more than 5 years post-surgery, regardless of suture type. However, surgical success remained high, and no delayed serious adverse events were reported.

Long-Term Costs of Minimally Invasive Sacral Colpopexy Compared to Native Tissue Vaginal Repair With Concomitant Hysterectomy.

STUDY OBJECTIVE: To determine the long-term costs of hysterectomy with minimally invasive sacrocolpopexy (MISCP) versus uterosacral ligament suspension (USLS) for primary uterovaginal prolapse repair. DESIGN: A hospital-based decision analysis model was built using TreeAge Pro (TreeAge Software Inc, Williamstown, MA). Those with prolapse were modeled to undergo either vaginal hysterectomy with USLS or minimally invasive total hysterectomy with sacrocolpopexy (MISCP). We modeled the chance of complications of the index procedure, prolapse recurrence with the option for surgical retreatment, complications of the salvage procedure, and possible second prolapse recurrence. The primary outcome was cost of the surgical strategy. The proportion of patients living with prolapse after treatment was the secondary outcome. SETTING: Tertiary center for urogynecology. PATIENTS: Female patients undergoing surgical repair by the same team for primary uterovaginal prolapse. INTERVENTIONS: Comparison analysis of estimated long-term costs was performed. MEASUREMENTS AND MAIN RESULTS: Our primary outcome showed that a strategy of undergoing MISCP as the primary index procedure cost $19 935 and that undergoing USLS as the primary index procedure cost $15 457, a difference of $4478. Furthermore, 21.1% of women in the USLS group will be living with recurrent prolapse compared to 6.2% of MISCP patients. Switching from USLS to MISCP to minimize recurrence risk would cost $30 054 per case of prolapse prevented. Additionally, a surgeon would have to perform 6.7 cases by MISCP instead of USLS in order to prevent 1 patient from having recurrent prolapse. CONCLUSION: The higher initial costs of MISCP compared to USLS persist in the long term after factoring in recurrence and complication rates, though more patients who undergo USLS live with prolapse recurrence.

Detection of Bacteria in Bladder Mucosa of Adult Females.

PURPOSE: Interstitial cystitis/bladder pain syndrome is a chronic urological condition diagnosed in nearly 8 million females in the United States. Whether urinary microbiota play an etiological role remains controversial. Most studies assessed the microbiota of interstitial cystitis/bladder pain syndrome patients with voided or catheterized urine as a proxy for bladder urothelium; however, urine may not be a true reflection of the bladder microbiota. Bladder biopsy tissue may provide a more accurate, and thus more clinically relevant, picture of bladder microbiota. MATERIALS AND METHODS: Bladder biopsy tissues were obtained from: (1) 30 females with interstitial cystitis/bladder pain syndrome (18-80 years old) via cystoscopically guided cold-cup biopsy following therapeutic bladder hydrodistention, and (2) 10 non-interstitial cystitis/bladder pain syndrome females undergoing pelvic organ prolapse repair. To detect bacteria, technical duplicates of each RNAlater-preserved biopsy were subjected to 16S rRNA gene sequencing. To visualize bacteria, paraformaldehyde-fixed, paraffin-embedded biopsies were subjected to a combined multiplexed fluorescence in situ hybridization and fluorescence immunohistochemistry assay and confocal microscopy. RESULTS: Bacteria were detected by 16S rRNA gene sequencing in at least 1 technical duplicate of most biopsies. The most abundant genus was Staphylococcus, followed by Lactobacillus; Escherichia was common but not abundant. There was no significant difference between interstitial cystitis/bladder pain syndrome patients and controls (P > .05). Combined fluorescence in situ hybridization and immunohistochemistry reproducibly detected 16S rRNA in epithelial cells and shed cells in the urothelium and lesioned areas and capillary walls in the lamina propria of human bladder biopsy tissue. CONCLUSIONS: We conclude that urothelial and urinary microbiota are similar but not identical in adult females.

Financial analysis of minimally invasive sacrocolpopexy compared with native tissue vaginal repair with concomitant hysterectomy.

INTRODUCTION: Minimally invasive sacrocolpopexy (MISCP) is increasingly used for uterovaginal prolapse, but comparative cost data of MISCP versus native tissue vaginal repair (NTR) are lacking. The objective was to determine the cost difference, from a hospital perspective, between MISCP and NTR performed with hysterectomy for uterovaginal prolapse. METHODS: This was a retrospective cohort study at a tertiary care center of women who underwent NTR or MISCP with concomitant hysterectomy in 2021. Hospital charges, direct and indirect costs, and operating margin (revenue minus costs) were obtained from Strata Jazz and compared using SPSS. RESULTS: A total of 82 women were included, 33 MISCP (25 robotic, 8 laparoscopic) versus 49 NTR. Demographic and surgical data were similar, except that MISCP had younger age (50.5 vs 61.1 years, p<0.01). Same-day discharge and estimated blood loss were similar, but operative time was longer for MISCP (204 vs 161 min, p<0.01). MISCP total costs were higher (US$17,422 vs US$13,001, p<0.01). MISCP had higher direct costs (US$12,354 vs US$9,305, p<0.01) and indirect costs (US$5,068 vs US$3,696, p<0.01). Consumable supply costs were higher with MISCP (US$4,429 vs US$2,089, p<0.01), but the cost of operating room time and staff was similar (US$7,926 vs US$7,216, p=0.07). Controlling for same-day discharge, anti-incontinence procedures and smoking, total costs were higher for MISCP (adjusted beta = US$4,262, p<0.01). Mean charges (US$102,060 vs US$97,185, p=0.379), revenue (US$22,214 vs US$22,491, p=0.929), and operating margin (US$8,719 vs US$3,966, p=0.134) were not statistically different. CONCLUSION: Minimally invasive sacrocolpopexy had higher costs than NTR; however, charges, reimbursement, and operating margins were not statistically significantly different between the groups.

Anterior approach sacrospinous hysteropexy: native tissue compared with mesh-augmented repair for primary uterovaginal prolapse management.

INTRODUCTION AND HYPOTHESIS: Anterior sacrospinous hysteropexy (SSH) was popularized by transvaginal mesh kits. Following mesh-kit market withdrawal, we hypothesized similar efficacy through native-tissue reattachment of the pubocervical fascia with fixation of the anterior cervix to the sacrospinous ligament. Few analyses for anterior native-tissue versus mesh-augmented SSH exist. METHODS: A retrospective analysis of women who underwent transvaginal anterior SSH between 01 January 2016 and 31 December 2022 was performed. Women who underwent a mesh-augmented (Uphold Lite Vaginal Support System™) versus native-tissue repair were compared. Composite success was defined as no bulge symptoms, no retreatment, and no recurrence beyond the hymen with apex nondescended > one third of the total vaginal length. Descriptive and bivariate statistics were obtained as indicated. RESULTS: Of 223 women screened, inclusion criteria were met by 124 (40 mesh-augmented; 84 native-tissue). There was no difference in pre-operative characteristics between groups. Composite success was demonstrated in 95.2% of women with a median follow-up of 224 days (range: 30-988). Two women in the mesh-augmented group reported bulge symptoms and underwent re-treatment with a pessary. Four women in the native-tissue group reported bulge symptoms; 3 underwent re-treatment (2 pessary, 1 surgery). There were no differences in composite success rates between groups (p=0.954). There were additionally no differences in intra-operative (p=0.752) or post-operative (p=0.292) complication rates between the groups. There were no mesh-related complications, including exposure or chronic pelvic pain. CONCLUSIONS: Ninety-five percent of women achieved surgical success and the use of mesh augmentation did not confer added benefit in terms of efficacy or complications when compared with native tissue. Further long-term data are needed to continue our assessment of native-tissue anterior SSH.

An assessment of urethral radiation exposure in the treatment of endometrial and rectal cancers.

INTRODUCTION AND HYPOTHESIS: Female survivors of endometrial and rectal cancers have increased risk of urinary incontinence. Survivors with prior radiation therapy are counseled against mesh incontinence surgery. We hypothesize that urethral radiation dose varies based on modality which may influence surgical risks. We aimed to demonstrate urethral radiation dose differences between vaginal brachytherapy (VBT) and external beam radiation therapy (EBRT). METHODS: This is a retrospective cohort study of women exposed to VBT for endometrial cancer and EBRT for rectal cancer. The urethra was contoured on CT imaging to calculate radiation doses in centigray (cGy). The primary outcome was the percent of treatment radiation dose estimated to be received by the urethra based on the volume dose to 0.2 cc of urethra. Secondary outcomes were point doses to the bladder neck, mid-urethra, and total mean urethral dose. Descriptive statistics described demographic characteristics. Bivariate analyses compared urethral radiation dose based on radiation modality. RESULTS: Between 2014-2017, 32 women treated were included: 18 with VBT and 14 with EBRT. Mean ± SD urethral volume doses were lower in VBT (1266 cGy ± 533, 42.2% of prescribed treatment dose) compared to EBRT (5051 cGy ± 192, 100.2% of prescribed treatment dose), p < 0.0001. VBT also had significantly lower mean total urethral dose and point doses to bladder neck and mid- urethra compared to EBRT (p < 0.0001). CONCLUSIONS: The female urethra is exposed to significantly less radiation in VBT compared to EBRT. These data highlight that modality of pelvic radiation should be considered in treatment counseling on urinary incontinence in women.

Long-term mesh exposure after minimally invasive total hysterectomy and sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: The objective was to evaluate total and incident mesh exposure rates at least 2 years after minimally invasive total hysterectomy and sacrocolpopexy. Secondary aims were to evaluate surgical success and late adverse events. METHODS: This extension study included women previously enrolled in the multicenter randomized trial of permanent vs delayed-absorbable suture with lightweight mesh for > stage II uterovaginal prolapse. Owing to COVID-19, women were given the option of an in-person (questionnaires and examination) or telephone visit (questionnaires only). The primary outcome was total and incident suture or mesh exposure, or symptoms suggestive of mesh exposure in women without an examination. Secondary outcomes were surgical success, which was defined as no subjective bulge, no prolapse beyond the hymen, and no pelvic organ prolapse retreatment, and adverse events. RESULTS: A total of 182 out of 200 previously randomized participants were eligible for inclusion, of whom 106 (58%) women (78 in-person and 28 via questionnaire only) agreed to the extension study. At a mean of 3.9 years post-surgery, the rate of mesh or suture exposure was 7.7% (14 out of 182) of whom only 2 were incident cases reported after 1-year follow-up. None reported vaginal bleeding or discharge, dyspareunia, or penile dyspareunia. Surgical success was 93 out of 106 (87.7%): 13 out of 94 (13.8%) failed by bulge symptoms, 2 out of 78 (2.6%) by prolapse beyond the hymen, 1 out of 85 (1.2%) by retreatment with pessary, and 0 by retreatment with surgery. There were no serious adverse events. CONCLUSIONS: The rate of incident mesh exposure between 1 and 3.9 years post-surgery was low, success rates remained high, and there were no delayed serious adverse events.

Characterizing the physical function decline and disabilities present among older adults with fecal incontinence: a secondary analysis of the health, aging, and body composition study.

OBJECTIVE: Unhealthy aging is associated with fecal incontinence (FI) and poor physical performance. The link between FI and physical performance in older adults is unknown. We aim to examine the longitudinal relationship between FI symptoms and physical performance among older US adults. METHODS: We analyzed a cohort of well-functioning, adults aged 70-79 years enrolled in the prospective cohort of the Health, Aging, and Body Composition study. Fecal incontinence symptoms were assessed at baseline using a validated question. Physical performance was determined by the expanded version of the Short Physical Performance Battery (HABC PBB), which includes an assessment of usual and fast walking speed and balance measures. Objective measures of physical performance were determined at baseline and year 4. Univariate and multivariate analyses compared physical performance based on presence of FI symptoms adjusting for important demographic and clinical covariates. RESULTS: Of the 2914 participants in the Health ABC cohort, 222 (8%) had FI symptoms and 2692 (92%) did not. Mean age and BMI were 73 years and 27 kg/m2, respectively. Older adults with FI symptoms demonstrated a clinically significant decline in total HABC PBB scores from baseline to year 4 of -0.33 (95% CI: -0.41, -0.25), a statistically significant difference compared to adults without FI symptoms (-0.26 [95% CI: -0.32, -0.20]), p = 0.04. Sub-scale components demonstrated greater deficits in narrow walk speed, p = 0.03, and non-significant trend in greater deficits in repeated chair rise pace and gait speed, p ≥ 0.05. CONCLUSIONS: Fecal incontinence symptoms are associated with clinically important declines in physical performance in older adults.

Safety and economics of an enhanced recovery after surgery protocol in pelvic reconstructive surgery.

INTRODUCTION AND HYPOTHESIS: We hypothesized that an enhanced recovery after surgery (ERAS) protocol for patients undergoing female pelvic reconstructive surgery would conserve hospital resources without compromising patient safety. METHODS: In June 2020, an ERAS protocol designed to promote same-day discharge was initiated that included pre-operative hydration, a urinary anesthetic, non-narcotic analgesia, perineal ice, a bowel regimen, enrollment of the family to assist with care, and communication regarding planned same-day discharge. We compared demographic, operative, hospital stay, complications, and cost data in patients undergoing pelvic organ prolapse or incontinence surgery over 4 sequential months pre (PRE; N = 82) and post (POST; N = 91) ERAS implementation using univariate statistics. RESULTS: There were no differences in demographics, operative details, or complications (p > 0.05). There were no significant differences in overall revenues or expenses (p > 0.05), but bed unit cost was significantly lower in the POST group ($210 vs $533, p < 0.0001). There was a trend toward an increased operating margin in POST patients ($4,554 vs $2,151, p = 0.1163). Significantly more POST surgeries were performed in an ambulatory setting (73.6% vs 48.8%, p = 0.0008) and resulted in same-day discharge (80.2% vs 50.0%, p = 0.0003). There were no differences in the rates of emergency room or unexpected clinic visits (p > 0.05). Prescribed post-operative opiate dose was significantly reduced in POST patients (p < 0.0001). CONCLUSIONS: In patients undergoing female pelvic reconstructive surgery, an ERAS protocol facilitated transfer of procedures to an ambulatory surgical site and permitted same-day discharge without increasing complications, clinic visits, or emergency room visits. It also reduced bed unit cost and may improve operating margins.

Chemokine therapy for anal sphincter injury in a rat model: a pilot study.

INTRODUCTION AND HYPOTHESIS: To determine whether delayed administration of CXCL12 alters anorectal manometric pressures and histology in rats following anal sphincterotomy compared to primary surgical repair alone. METHODS: Adult female rats were divided into three groups: A, a control group that did not undergo surgery; B, anal sphincterotomy with primary surgical repair; C, anal sphincterotomy with primary surgical repair and intra-sphincteric injection of CXCL12 at 6 weeks post-injury. All rats underwent anal manometry measurements at baseline and at 6 and 12 weeks post-injury. Histologic analysis of the anal sphincters was also performed. RESULTS: At baseline and 6 weeks, there were no statistically significant differences among D, Tmax and P∆ of Groups A, B and C. At 12-week manometry, the total duration of contractions on anal manometry was significantly less in Group C compared to Groups A and B (3.65, 5.5, 5.3 p < 0.01) as was time to peak of contraction at 12 weeks (1.6, 2.1, 3.1, p < 0.01); however, group C had a significantly higher P∆ at 12 weeks compared to Groups A and B (2.25, 1.4, 0.34, p < 0.01). There were no statistically significant differences in the ratio of muscle to collagen at the site of injury; however, muscle fibers were significantly smaller in group C and less per bundle than the other groups. CONCLUSIONS: Administration of chemokine therapy at 6 weeks post-repair using CXCL12 enhanced the magnitude of anal sphincter contractions in a rat model of anal sphincter injury but decreased overall duration of contraction. Increased anal sphincter contraction magnitude was not explained by histologic differences in explanted specimens.

Mesh Exposure Following Vaginal Versus Laparoscopic Hysterectomy at the Time of Sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: To compare vaginal mesh exposure rates, adverse events and composite failure within 1 year postoperatively in patients who undergo vaginal hysterectomy with vaginal mesh attachment (TVH) versus laparoscopic hysterectomy with abdominal mesh attachment (TLH) for minimally invasive sacrocolpopexy. METHODS: This multicenter retrospective cohort study is a secondary analysis of data collected retrospectively at one institution and the multicenter randomized control PACT trial. Women were excluded for no follow-up between 9 months and 2 years postoperatively or undergoing concurrent non-urogynecologic procedures. RESULTS: Between 2010 and 2019, 182 patients underwent TLH and 132 TVH. There were 15 (4.8%) vaginal mesh exposures: 12 (6.6%) in the TLH and 3 (2.3%) in the TVH group (p = 0.133) with zero mesh erosions. Logistic regression analysis for mesh exposure in the TLH vs. TVH groups controlling for BMI, posterior repair and surgeon training also showed no significant difference (OR 4.8, 95% CI 0.94, 24.8, p = 0.059). The overall intraoperative complication rate was low (19/314, 6.1%) with a higher rate of bladder injury in the TLH group (4.4% vs. 0.8%, p = 0.049). The TLH group had a higher rate of UTI (8.2% vs. 2.3%, p = 0.027) and clean intermittent catheterization (11% vs. 3%, p = 0.009). At 1-year follow-up, there was no difference in composite failure (6%), bulge symptoms (5%) or retreatment (1%) between groups. CONCLUSIONS: At 1 year, there is no significant difference in vaginal mesh exposure rates between vaginal hysterectomy with vaginal mesh attachment and laparoscopic hysterectomy with abdominal mesh attachment. Both groups have equal efficacy with low rates of complications.

Voiding function after sacrocolpopexy versus native tissue transvaginal repair for apical pelvic organ prolapse in an ERAS era: A retrospective cohort study.

OBJECTIVE: The objectives of this study were to compare time to return of voiding function and associated complications in women undergoing minimally invasive sacrocolpopexy (SCP) versus transvaginal native tissue repair in patients with same-day or early discharge. METHODS: This was a retrospective cohort study conducted at a tertiary care center. The electronic medical record system was queried for women who underwent native tissue vaginal repair or SCP for apical prolapse between March and December 2020 using CPT codes for sacrocolpopexy (57425), extraperitoneal (57282), and intraperitoneal colpopexy (57283). Voiding success was our primary outcome and was defined by a postvoid residual < 150 ml. Secondary outcomes included catheter days and urinary tract infections. The total number of participants was based on a power calculation using internal institutional rates. Participants were compared based on the surgical approach. A multivariate regression analysis was performed to assess for confounding factors. RESULTS: We included 134 women: 63 SCP and 71 native tissue. The failure rate of the first postoperative voiding trial was 34 vs. 11% (odds ratio: 4.91; 95% CI 1.96-12.3, p < 0.01) in the vaginal and SCP groups, respectively. Both groups had a similar success rate of a second voiding trial (100% in SCP group vs. 95.7% in the vaginal repair group, p = 1). The total number of days (3.108 vs. 1.603 days, p < 0.01) to return of bladder function, postoperative urinary tract infections (23.9 vs. 6.35%, p < 0.01) and emergency department visits (15.5 vs. 1.59%, p < 0.01) were all higher in the vaginal repair group. CONCLUSIONS: Vaginal apical native tissue repair had a fivefold greater risk of acute postoperative urinary retention compared to sacrocolpopexy in addition to increased rates of post-operative urinary tract infection and emergency department visits for urinary tract concerns.

Pulsed electromagnetic field (PEMF) as an adjunct therapy for pain management in interstitial cystitis/bladder pain syndrome.

INTRODUCTION AND HYPOTHESIS: Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) often experience chronic pelvic and even systemic pain that can be difficult to clinically manage. Pulsed electromagnetic field (PEMF) therapy, a non-invasive strategy that has shown significant efficacy for pain reduction in other chronic pain conditions, may provide benefit for pain management in patients with IC/BPS. METHODS: PEMF delivery to patients occurs via a bio-electromagnetic-energy device which consists of a flexible mat (180 × 50 cm) that the patient lies on for systemic, full-body delivery and/or a flexible pad (50 × 15 cm) for targeted delivery to a specific body region (e.g., pelvic area). The duration of individual sessions, number of sessions per day, total number of sessions, and follow-up observation period vary between previously published studies. Positive outcomes are typically reported as a significant reduction in visual analog scale (VAS) pain score and functional improvement assessed using validated questionnaires specific to the condition under study. RESULTS AND CONCLUSIONS: The use of PEMF has been evaluated as a therapeutic strategy for pain management in several clinical scenarios. Randomized, double-blinded, placebo-controlled trials have reported positive efficacy and safety profiles when PEMF was used to treat non-specific low back pain, patellofemoral pain syndrome, chronic post-operative pain, osteoarthritis-related pain, rheumatoid arthritis-related pain, and fibromyalgia-related pain. Based on these positive outcomes in a variety of pain conditions, clinical trials to evaluate whether PEMF can provide a safe, non-invasive therapeutic approach to improve symptoms of chronic pain and fatigue in patients with IC/BPS are warranted.

Functional genomic analyses of IC/BPS patient subgroups: a pilot study.

INTRODUCTION: To further facilitate understanding of disease pathophysiology and patient stratification in interstitial cystitis/bladder pain syndrome (IC/BPS), we utilized molecular phenotyping to compare three clinically distinct IC/BPS patient subgroups. MATERIALS AND METHODS: Total RNA (miRNA and mRNA) was isolated via standard protocols from IC/BPS patient bladder biopsies and assayed on whole genome and microRNA expression arrays. Data from three patient subgroups (n = 4 per group): (1) low bladder capacity (BC; ≤ 400 cc) without Hunner's lesion, (2) low BC with Hunner's lesion, and (3) non-low BC (> 400 cc) were used in comparative analyses to evaluate the influence of BC and HL on gene expression profiles in IC/BPS. RESULTS: The BC comparison (Group 1 v 3) identified 54 miRNAs and 744 mRNAs. Eleven miRNAs mapped to 40 genes. Hierarchical clustering of miRNA revealed two primary clusters: (1) 3/4 low BC patients; (2) 4/4 non-low and 1/4 low BC patients. Clustering of mRNA provided clear separation based on BC. The HL comparison (Group 1 v 2) identified 16 miRNAs and 917 mRNAs. 4 miRNAs mapped to 13 genes. Clustering of miRNA and mRNA revealed clear separation based on HL status. CONCLUSIONS: Significant molecular differences in IC/BPS were found to be associated with the low BC phenotype (e.g., an upregulation of cell proliferation and inflammation marker genes), as well as additional molecular findings that further define the HL+ phenotype (e.g., upregulation of genes involved in bioenergetics reactions) and suggest oxidative stress may play a role.

An analysis of diversity within academic urology leadership.

INTRODUCTION: Women, underrepresented minorities, and international medical graduates are underrepresented in urology. We sought to compare demographics of leaders in academic urology to urology faculty and academic medical faculty. MATERIALS AND METHODS: The Association of American Medical Colleges provided academic medical faculty demographics. Women, underrepresented minorities, and international medical graduates in leadership roles (department/division chair or full professor) were identified. Fisher's exact tests were performed to compare proportions of those groups in urology leadership to academic urology, academic medicine leadership, and academic medicine. RESULTS: In 2019, there were 179,105 faculty in academic medicine with 41,766 in leadership and 1,614 faculty in urology with 567 in leadership. Significantly fewer women were in urology leadership compared to academic urology (7.4% vs. 22.0%, p < 0.0001), academic medical leadership (7.4% vs. 25.0%, p < 0.0001), and academic medicine (7.4% vs. 42.0%, p < 0.0001). Significantly fewer underrepresented minorities were in urology leadership compared to academic medicine (6.9% vs. 9.4%, p = 0.04) with no significant difference when compared to urology faculty (6.9% vs. 8.1%, p = 0.4) or medical faculty leadership (6.9% vs. 6.4%, p = 0.6). Significantly more international medical graduates were in urology leadership compared to across academic urology, (32% vs. 24%, p = 0.0006), but significantly fewer than those in leadership across all medical specialties (32% vs. 40%, p = 0.0001). CONCLUSIONS: Women and underrepresented minorities are significantly underrepresented in academic urologic leadership while international medical graduates are statistically overrepresented. Considering calls for diversity, equity, and inclusion, these data highlight a need for increased representation in leadership positions in academic urology.

Hydrodistention does not alter bladder gene expression profiles in patients with non-Hunner lesion interstitial cystitis/bladder pain syndrome.

AIMS: Gene expression profiling of bladder biopsies in patients with interstitial cystitis/bladder pain syndrome (IC/BPS), typically obtained following therapeutic bladder hydrodistention (HOD), is used to improve our understanding of molecular phenotypes. The objective of this study was to determine if the HOD procedure itself impacts the biopsy gene expression profile and, by extension, whether biopsies from non-HOD bladders are appropriate controls. METHODS: Bladder biopsies were obtained just before HOD and immediately following HOD from 10 consecutively recruited IC/BPS patients undergoing therapeutic HOD. Biopsies were also obtained from four non-IC/BPS patients who did not undergo HOD (controls). Total RNA was isolated from each of the 24 samples and used to query whole-genome microarrays. Differential gene expression analysis was performed to compare expression profiles of IC/BPS biopsies before and after HOD, and between IC/BPS and control biopsies. RESULTS: Principal component analysis revealed complete separation between gene expression profiles from IC/BPS and control samples (q ≤ 0.05) and while IC/BPS samples before and after HOD showed no significant differences in expressed genes, 68 transcripts were found to be significantly different between IC/BPS and control samples (q ≤ 0.05). CONCLUSIONS: The bladder HOD procedure itself does not significantly change gene expression within the IC/BPS patient bladder, a finding that provides evidence to support the use of biopsies from non-IC/BPS patients that have not undergone HOD as controls for gene expression studies.