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.

Two-year outcomes of the ARTISAN-SNM study for the treatment of urinary urgency incontinence using the Axonics rechargeable sacral neuromodulation system.

AIMS: Sacral neuromodulation (SNM) is a guideline-recommended treatment with proven therapeutic benefit for urinary urgency incontinence (UUI) patients. The Axonics® System is the first Food and Drug Administration-approved rechargeable SNM system and is designed to deliver therapy for a minimum of 15 years. The ARTISAN-SNM study was designed to evaluate UUI participants treated with the Axonics System. Two-year follow-up results are presented. METHODS: One hundred and twenty-nine UUI participants underwent implantation with the Axonics System. Therapeutic response rate, participant quality of life (QoL), and satisfaction were determined using 3-day voiding diaries, ICIQ-OABqol, and satisfaction questionnaires. Participants were considered responders if they had a 50% or greater reduction in UUI episodes post-treatment. As-treated and Completers analyses are presented. RESULTS: At 2 years, 93% of the participants (n = 121 Completers at 2 years) were therapy responders, of which 82% achieved ≥ 75% reduction in UUI episodes and 37% were dry (100% reduction). Daily UUI episodes reduced from 5.6 ± 0.3 at baseline to 1.0 ± 0.2 at 2 years. Statistically significant improvements in ICIQ-OABqol were reported. All participants were able to recharge their device and 94% of participants reported that the recharging frequency and duration were acceptable. Participant demographics nor condition severity were correlated with clinical outcomes or recharging experience. No unanticipated or serious device-related adverse events occurred. CONCLUSIONS: At 2 years, participants treated with the Axonics System demonstrated sustained safety and efficacy, high levels of satisfaction with therapy and recharging. Participant-related factors were not associated with efficacy or recharging outcomes, indicating the reported results are applicable to a diverse population.

Extraction of a large vaginal calculus utilizing an ear, nose, throat mallet and osteotomes.

BACKGROUND: Previous case reports on vaginal calculi extraction have described the removal of small calculi facilitated via episiotomy or transabdominal incision. This surgical video demonstrates a novel technique of transvaginal extraction of a large calculus utilizing an ear, nose, and throat (ENT) mallet and osteotomes. CASE: An 86-year-old female with urgency incontinence and limited mobility presented with obstipation and was found to have an 8.8 cm vaginal calculus. She had a history of prior vaginal mesh exposure after a mid-urethral sling that was managed expectantly without surgical resection. Cystourethroscopy and anoscopy excluded fistula. The calculus was extracted utilizing an ENT mallet and osteotomes in < 90 min, and no recurrent vaginal mesh exposure was identified. CONCLUSION: An ENT mallet and osteotomes can be safely utilized to expedite extraction of a vaginal calculus.

Percutaneous tibial nerve stimulation for the treatment of interstitial cystitis/bladder pain syndrome: a pilot study.

OBJECTIVES: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain condition that requires multimodal management. The American Urologic Association includes sacral neuromodulation in the treatment algorithm for refractory IC/BPS. We sought to determine the rate of overall symptom improvement of IC/BPS symptoms, using validated measures, after treatment with percutaneous tibial nerve stimulation (PTNS), a form of peripheral neuromodulation. METHODS: This was a single-arm, dual-center, pilot study examining a standard PTNS protocol in subjects with IC/BPS. Our primary outcome was subject response of "moderately" or "markedly improved" on the Global Response Assessment (GRA) scale after 12-weekly PTNS sessions. Assuming a 60% response rate, 24 subjects were needed to detect a response rate between 40 and 80% with 95% confidence. Secondary objectives included change in urinary frequency on a 24-h bladder diary, bladder pain as measured by VAS and responses to validated questionnaires for pelvic pain and IC/BPS. RESULTS: Of 21 subjects enrolled, 16 initiated and 10 completed the PTNS treatment course. The GRA response rate was 40% at week 6 and 30% at week 12. Seventy percent of the cohort had some degree of improvement. There were no adverse events. CONCLUSIONS: While only a minority of subjects with IC/BPS were responders to PTNS per GRA criteria, 70% of the cohort had some degree of improvement. Due to low recruitment and loss to follow-up, we did not achieve our predetermined significance. However, our promising findings add to the limited literature on this subject.

Treatment of Urinary Urgency Incontinence Using a Rechargeable SNM System: 6-Month Results of the ARTISAN-SNM Study.

PURPOSE: Sacral neuromodulation is a guideline recommended treatment of urinary dysfunction and fecal incontinence in patients in whom conservative treatments have failed. Historically sacral neuromodulation has been delivered using a nonrechargeable device with an average life span of 4.4 years. Surgery is required to replace the implanted neurostimulator due to battery depletion. Implantation of a long-lived implanted neurostimulator can eliminate the need for replacement surgeries, potentially reducing patient surgical risks and health care costs. The Axonics r-SNM System™ is a miniaturized, rechargeable sacral neuromodulation system designed to deliver therapy for at least 15 years. The ARTISAN-SNM (Axonics® Sacral Neuromodulation System for Urinary Urgency Incontinence Treatment) study is a pivotal study using rechargeable sacral neuromodulation therapy to treat urinary urgency incontinence. Six-month results are presented. MATERIALS AND METHODS: A total of 129 eligible patients with urinary urgency incontinence were treated. All participants were implanted with a tined lead and the rechargeable sacral neuromodulation system in a nonstaged procedure. Efficacy data were collected using a 3-day bladder diary, the validated ICIQ-OABqol (International Consultation on Incontinence Questionnaire Overactive Bladder quality of life) questionnaire and a participant satisfaction questionnaire. Therapy responders were identified as participants with a 50% or greater reduction in urinary urgency incontinence episodes compared to baseline. We performed an as-treated analysis in all implanted participants. RESULTS: At 6 months 90% of participants were therapy responders. The mean ± SE number of urinary urgency incontinence episodes per day was reduced from 5.6 ± 0.3 at baseline to 1.3 ± 0.2. Participants experienced a clinically meaningful 34-point improvement on the ICIQ-OABqol questionnaire. There were no serious device related adverse events. CONCLUSIONS: The Axonics r-SNM System is safe and effective with 90% of participants experiencing clinically and statistically significant improvements in urinary urgency incontinence symptoms.

One-year outcomes of the ARTISAN-SNM study with the Axonics System for the treatment of urinary urgency incontinence.

AIMS: Sacral neuromodulation (SNM) is a guideline-recommended treatment for voiding dysfunction including urgency, urge incontinence, and nonobstructive retention as well as fecal incontinence. The Axonics® System is a miniaturized, rechargeable SNM system designed to provide therapy for at least 15 years, which is expected to significantly reduce revision surgeries as it will not require replacement as frequently as the non-rechargeable SNM system. The ARTISAN-SNM study is a pivotal study designed to treat patients with urinary urgency incontinence (UUI). Clinical results at 1-year are presented. METHODS: A total of 129 eligible UUI patients were treated. All participants were implanted with a quadripolar tined lead and neurostimulator in a single procedure. Efficacy data were collected using a 3-day bladder diary, a validated quality of life questionnaire (ICIQ-OABqol), and a participant satisfaction questionnaire. Therapy responders were defined as participants with ≥50% reduction in UUI episodes compared to baseline. Data were analyzed on all 129 participants. RESULTS: At 1 year, 89% of the participants were therapy responders. The average UUI episodes per day reduced from 5.6 ± 0.3 at baseline to 1.4 ± 0.2. Participants experienced an overall clinically meaningful improvement of 34 points on the ICIQ-OABqol questionnaire. All study participants (100%) were able to recharge their device at 1 year, and 96% of participants reported that the frequency and duration of recharging was acceptable. There were no serious device-related adverse events. CONCLUSIONS: The Axonics System is safe and effective at 1 year, with 89% of participants experiencing clinically and statistically significant improvements in UUI symptoms.

An Internet-based survey to evaluate the comfort and need for further pubovaginal sling training.

INTRODUCTION AND HYPOTHESIS: The pubovaginal sling (PVS) dates to the 1940s as an efficacious surgical treatment for stress urinary incontinence (SUI). Recently, it has been replaced by the midurethral sling (MUS). Since 2008, international regulatory agencies increased regulation and issued warnings on vaginal mesh for repair of pelvic organ prolapse (POP), which has led to increased scrutiny of the MUS. Thus, the need for surgical comfort with PVS is resurfacing. We sought to evaluate the surgical practice patterns among international urogynecologists for the treatment of SUI and identify whether a need and interest for more training exists. METHODS: We developed a short, Internet-based survey for members of the International Urogynecological Association (IUGA). Descriptive analyses, binomial and multivariate logistic regressions were calculated to determine significant associations. RESULTS: Among 556 members who responded to the survey, 72% did not offer PVS in practice. Among those who did, there was as significant relationship between offering PVS and practicing in the United States, board-certification in urogynecology, PVS exposure in training, increasing number of PVS performed during training, and comfort with PVS. Members interested in further PVS training were younger, less comfortable with PVS, performed fewer PVS, or had no exposure in training. CONCLUSION: Most IUGA members do not offer PVS in clinical practice. As would be expected, members who performed more PVS in training and were more comfortable with PVS were likely to offer it to patients. Our results highlight a learning gap, especially among younger providers who are not comfortable with PVS and desire further training in this procedure.

1.7 micron optical coherence tomography for vaginal tissue characterization in vivo.

OBJECTIVES: Optical coherence tomography (OCT) can noninvasively visualize in vivo tissue microstructure with high spatial resolution that approaches the histologic level. Currently, OCT studies in gynecology are few and limited to a conventional 1.3 µm center wavelength swept light source which provides high spatial resolution but limited penetration depth. Here, we present a novel endoscopic OCT system with improved penetration depth and high resolution. METHODS: A novel endoscopic OCT system was developed based on a 1.7 µm swept source laser, which is capable of deeper tissue penetration due to its longer wavelength. To evaluate the performance of system, we imaged the human vaginas in vivo with both conventional 1.3 and 1.7 µm endoscopic OCT systems. RESULTS: With the 1.7 µm endoscopic OCT system, imaging depth was improved by more than 25%, allowing better visualization of the lamina propria and clear contrast of the epithelial layer from the surrounding tissues. CONCLUSION: The significantly improved performance of the novel 1.7 µm OCT imaging system demonstrates its potential use as a minimally-invasive monitoring tool of vaginal health in gynecologic practice. Lasers Surg. Med. 51:120-126, 2019. © 2018 Wiley Periodicals, Inc.

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.

OCT angiography in the monitoring of vaginal health.

Fractional-pixel CO2 laser therapy shows promise for treating the genitourinary syndrome of menopause (GSM). Nevertheless, it remains controversial in the field of female pelvic medicine. This is due to the inherent difficulties in obtaining noninvasive biopsies to evaluate the treatment's efficacy and safety objectively. To address this challenge, we developed a noninvasive intravaginal optical coherence tomography (OCT)/OCT angiography (OCTA) endoscopic system, whose probe features a shape identical to the laser treatment probe. This system can provide high-resolution OCT images to identify the microstructure of vaginal tissue and visualize the vasculature network in vivo. We conducted clinical research on 25 post-menopausal patients with GSM. OCT/OCTA scans were acquired at four different locations of the vagina (distal anterior, distal posterior, proximal anterior, and proximal posterior) during the whole laser treatment session. A U-Net deep learning model was applied to segment the vaginal epithelium for assessing vaginal epithelial thickness (VET). Blood vessel density and VET were quantified to monitor the efficacy of fractional-pixel CO2 laser therapy. Statistical correlation analyses between these metrics and other clinical scores were conducted, validating the utility of our system. This OCT/OCTA endoscopic system has great potential to serve as a noninvasive biopsy tool in gynecological studies to screen, evaluate, and guide laser treatment for GSM.

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.

Fecal Putative Uropathogen Abundance and Antibiotic Resistance Gene Carriage in Women With Refractory Recurrent Urinary Tract Infection Treated With Fecal Microbiota Transplantation.

OBJECTIVE: The aims of this study were to describe the fecal relative abundance of potentially uropathogenic bacteria and to analyze antibiotic resistance genes before and after fecal microbiota transplantation in women with recurrent urinary tract infection (UTI). METHODS: Shotgun sequencing was performed on fecal samples from 3 donors and 4 women with recurrent UTI who underwent transplantation. Recipient samples were sequenced at baseline and at 4 time points through 6 months postintervention. Relative fecal uropathogen abundance was analyzed by species and participant using descriptive statistics. Antibiotic resistance gene abundance was assigned, normalized, and compared between donors and recipients at baseline and postintervention using an abundance bar plot, nonmetric multidimensional scaling, and pairwise permutational multivariate analysis of variance. RESULTS: The median (range) relative abundance of Escherichia coli in all fecal samples from women with recurrent UTI was 0% (0%-5.10%); Enterococcus faecalis, 0% (0%-0.20%); Enterococcus faecium, 0% (0%-1.90%); Klebsiella pneumoniae, 0% (0%-0.10%); and Pseudomonas aeruginosa, 0% (0%-0.10%). Gut microbes carried genes conferring resistance to antibiotics used for UTI. No significant difference was seen in antibiotic resistance gene carriage after transplantation compared with baseline (P=0.22, R2=0.08 at 3 months). Antibiotic gene composition and abundance were significantly associated with the individual from whom the sample came (P=0.004, R2=0.78 at 3 months). CONCLUSIONS: Exploratory analysis of gut microbiomes in women with recurrent UTI identifies no or low relative putative uropathogen abundance for all species examined. Antibiotic resistance gene carriage persisted after fecal microbiota transplantation, although conclusions are limited by small sample size.

Vulvovaginal involvement in Stevens-Johnson syndrome and toxic epidermal necrolysis: management and techniques used to reduce gynecologic sequelae.

BACKGROUND: Vulvovaginal involvement in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) is common, likely underdiagnosed, and can result in severe sequelae if not managed acutely. There are few studies on acute management of vulvovaginal SJS/TEN. Current recommendations are predominantly based on expert opinion. We aimed to determine the frequency of vulvovaginal involvement in SJS/TEN at a single institution, identify treatment modalities, and assess outcomes at a tertiary care burn center. METHODS: This is a retrospective review of vulvovaginal SJS/TEN cases between 2009 and 2019. Demographic and clinical data including exam findings, treatment regimens, and outpatient follow-up were collected from the electronic medical record. RESULTS: Vulvovaginal involvement was observed in 12.7% (19/149) of cases of female patients with SJS/TEN. The mean age was 38.7 years (SD 23.6), and 21% (4/19) of patients were pediatric (age 9-18). Vulvar involvement was seen in 47.3% (9/19), and vulvar plus vaginal involvement was reported in 42.1% (8/19). Treatment regimens were variable until 2017, at which time institutional guidelines were implemented including application of ultrapotent topical steroid, vaginal estrogen, and menstrual suppression. Gynecology follow-up occurred in 15.7% (3/19) of cases. One complication of superficial vaginal agglutination was noted and was successfully treated in the office with blunt dissection. CONCLUSION: The most common treatment modalities employed at our institution included application of ultrapotent topical steroid, vaginal estrogen, and menstrual suppression. While follow-up was limited for our patient population, we propose an algorithm to prevent long-term sequalae of vulvovaginal SJS/TEN. Gynecologic surveillance is recommended to reduce urogynecologic sequelae.

Optical coherence tomography evaluation of vaginal epithelial thickness during CO2 laser treatment: A pilot study.

Genitourinary syndrome of menopause (GSM) negatively affects more than half of postmenopausal women. Energy-based therapy has been explored as a minimally invasive treatment for GSM; however, its mechanism of action and efficacy is controversial. Here, we report on a pilot imaging study conducted on a small group of menopause patients undergoing laser treatment. Intravaginal optical coherence tomography (OCT) endoscope was used to quantitatively monitor the changes in the vaginal epithelial thickness (VET) during fractional-pixel CO2 laser treatment. Eleven patients with natural menopause and one surgically induced menopause patient were recruited in this clinical study. Following the laser treatment, 6 out of 11 natural menopause patient showed increase in both proximal and distal VET, while two natural menopause patient showed increase in VET in only one side of vaginal tract. Furthermore, the patient group that showed increased VET had thinner baseline VET compared to the patients that showed decrease in VET after laser treatment. These results demonstrate the potential utility of intravaginal OCT endoscope in evaluating the vaginal tissue integrity and tailoring vaginal laser treatment on a per-person basis, with the potential to monitor other treatment procedures.

Thirty-six-month Prospective Study of Transvaginal Bovine Graft vs Native Tissue Repair for the Treatment of Pelvic Organ Prolapse.

OBJECTIVE(S): To compare the safety and effectiveness of dermal bovine transvaginal graft, Xenform, to native tissue in the surgical treatment of anterior and/or apical pelvic organ prolapse. This study was designed in conjunction with Food and Drug Administration requirements. METHODS: This was a prospective, non-randomized, parallel cohort, multi-center trial. The primary objective was to demonstrate noninferiority between transvaginal graft and native tissue repair at 36 months compared to baseline. Treatment success was based on a composite of objective and subjective measures. The co-primary outcome was the rate of serious device- or procedure-related adverse events. A total of 228 patients at 25 sites were included in the study arm and 485 patients underwent native tissue repair. Propensity score stratification was applied to achieve balance between treatment groups. Study outcomes were compared in per protocol and intent-to-treat analysis. RESULTS: The primary outcome, treatment success at 36 months, was 83.6% (191/228) for transvaginal graft and 80.5% (390/485) native tissue repair (0.2%, 90% confidence interval [-5.6% to 5.9%]), demonstrating noninferiority at a preset margin of -12%. The overall rate of severe adverse events was 5.3% (12/228) in transvaginal graft vs 2.7% (13/485) in native tissue repair groups. The study group demonstrated noninferiority in serious adverse events at the preset margin of 11.6% (2.0%, 90% confidence interval [-0.8% to 4.7%]). There were no reports of graft erosion, and graft exposure rates were low (0.9% [2/228]). CONCLUSIONS: Transvaginal repair of anterior and/or apical prolapse with a biological graft is noninferior to traditional native tissue repair in effectiveness and safety at 36 months.

A Non-Invasive Determination of LOXL1 and Fibulin-5 Levels in the Vaginal Secretions of Women with and Without Pelvic Organ Prolapse.

OBJECTIVES: The aim of this study was to determine if lysyl oxidase-like 1 (LOXL1) and Fibulin-5 (Fib-5), two crucial proteins in the elastin metabolism pathway, are detectable in the vaginal secretions of women with and without pelvic organ prolapse (POP). We then sought to quantify levels of these proteins in relation to prolapse. METHODS: Vaginal secretions were obtained from 48 subjects (13 (27.1%) without and 35 (72.9%) with POP-Q Stage 2-4 prolapse). Eleven (22.9%) subjects were premenopausal and 37 (77.1%) were postmenopausal. Presence of LOXL-1 and Fibulin-5 within specimens were first identified via western blotting. Enzyme-Linked Immunosorbent Assays specific for LOXL1 and Fibulin-5 were conducted to quantify total protein secretion. RESULTS: LOXL1 was detected in 45/48 (93.8%) and Fibulin-5 was seen in 24/48 (50%) of subjects. LOXL1 values were lower in women without prolapse (13.3 ng/100 mg median, 24.4 IQR) vs. those with prolapse (26.4 ng/100 mg, 102.2 IQR). On multivariate analysis controlling for age, women with prolapse had a 544% (p=0.0042 higher LOXL1 protein level compared to those without. There was no significant differences in LOXL1 or Fibulin-5 protein detection with relation to menopausal status in bivariate analysis. CONCLUSIONS: This is the first published report of non-invasively measuring urogenital LOXL1 and Fibulin-5. In vaginal secretions, LOXL1 protein is higher in subjects with POP than those without.

A Randomized Controlled Trial Assessing the Impact of Opioid-Specific Patient Counseling on Opioid Consumption and Disposal After Reconstructive Pelvic Surgery.

OBJECTIVES: This study aims to determine the effect of opioid-specific counseling on postdischarge opioid consumption and opioid storage/disposal patterns after reconstructive pelvic surgery. METHODS: In this multicenter randomized-controlled trial, participants were randomized to standard generalized counseling or opioid-specific perioperative counseling. Opioid-specific counseling was provided at the preoperative and 2-week postoperative visits with educational handouts about the risks of opioids and U.S. Food and Drug Administration recommendations for appropriate opioid storage and disposal. The primary outcome was morphine milligram equivalent (MME) consumption between hospital discharge and 2 weeks postoperatively. Secondary outcomes included opioid storage 2 weeks postoperatively, opioid disposal 6 weeks postoperatively, and rate of opioid refills. RESULTS: Among 70 opioid-specific and 65 standard counseling participants, there were no significant differences in demographic characteristics, type of surgery, concomitant hysterectomy, or perioperative complications. For the primary outcome, there was no significant difference in median opioid consumption between the 2 arms. Median (interquartile range) postdischarge MME consumption for all participants was 15 mg (0-75). Forty percent of participants denied postdischarge MME consumption. For secondary outcomes, there were no significant differences in appropriate opioid storage between groups. The appropriate disposal rate of unused opioid tablets 6 weeks after surgery was higher among participants who received opioid-specific counseling. The rate of opioid refill was 7.4%. CONCLUSIONS: Opioid-specific counseling did not affect postdischarge consumption but increased the disposal rate of unused opioid tablets 6 weeks postoperatively. Opioid-specific counseling could minimize the potential for opioid misuse by reducing the number of unused opioid tablets in patients' possession after surgery.