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.

Predicting the return of bladder function following vaginal native tissue repair using data from a suprapubic catheter regimen.

AIMS: To evaluate time to return of normal voiding function following native tissue vaginal reconstruction and evaluate risk factors for postoperative urinary retention (POUR). METHODS: A retrospective cohort analysis of women undergoing vaginal reconstruction and suprapubic catheter with standardized regimen for voiding trials. Postvoid residual <150 ml at 4 h post catheter clamping was used as surrogate marker for return of bladder function. Univariate and multivariate regression analyses were used to identify risk factors for return of bladder function >4 days after surgery. RESULTS: Between 2013 and 2018, 148 women underwent surgery, 124 were analyzed. Mean age was 67 years (±11.1), 62.9% (n = 78) had greater than or equal to stage 3 prolapse. Mean time to return of bladder function: 4.1 days (±3.1). Significant risk factors for >4 days to return of bladder function on univariate analysis included (mean ± SD): surgery length (150.4 min ±44.6) (odds ratio [OR], 1.24; confidence interval [CI], 1.12, 1.38); anesthesia length (228.1 min ±53.5) (OR, 1.12; CI: 1.04, 1.23); length of stay (2.2 days ±2.7) (OR, 2.43; CI: 1.11, 5.35); hysterectomy (OR, 3.10; CI: 1.39, 6.90); estimated blood loss (124.4 ml ±64.8) (OR, 1.39; CI: 1.04, 1.87). Postmenopausal status was protective (OR, 0.17; CI: 0.03, 0.92.). On multivariate analysis, significant findings were diabetes mellitus (OR, 0.18; CI: 0.04, 0.93) and surgery length (OR, 1.21; CI: 1.06, 1.38). CONCLUSIONS: Hysterectomy, surgical length and estimated blood loss were significantly associated with delayed return of bladder function after native tissue vaginal reconstruction. This data can help clinicians tailor postoperative voiding trials after failed initial attempt.

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.

Histological evidence supports low anesthetic bladder capacity as a marker of a bladder-centric disease subtype in interstitial cystitis/bladder pain syndrome.

INTRODUCTION AND HYPOTHESIS: Low anesthetic bladder capacity has been shown to be a biomarker for bladder-centric interstitial cystitis/bladder pain syndrome (IC/BPS). The goal of this study was to determine if histopathological evidence from bladder biopsies supports anesthetic bladder capacity (BC) as a marker to distinguish a bladder-centric IC/BPS subtype. METHODS: From a review of our large IC/BPS cohort of patients undergoing hydrodistention, we identified a total of 41 patients with low BC (≤ 400 ml); an additional 41 consecutive patients with BC > 400 ml were selected as the comparator group. The original bladder mucosal biopsy pathology slides were re-reviewed by a single pathologist (blinded to patient information) using a standardized grading scale developed for this study. RESULTS: Histologically, the low BC subjects exhibited higher levels of acute inflammation (p = 0.0299), chronic inflammation (p = 0.0139), and erosion on microscopy (p = 0.0155); however, there was no significant difference in mast cell count between groups (p = 0.4431). There was no significant gender difference between the groups; female patients were the majority in both groups (low BC: 94.12%, non-low BC: 100%; p = 0.1246). Individuals in the low BC group were older (p < 0.0001), had a higher incidence of Hunner's lesions on cystoscopy (p < 0.0001), and had significantly higher scores, i.e., more bother symptoms, on two IC/BPS questionnaires (ICPI, p = 0.0154; ICSI, p = 0.0005). CONCLUSIONS: IC/BPS patients with low anesthetic bladder capacity have histological evidence of significantly more acute and chronic inflammation compared with patients with a non-low bladder capacity. These data provide additional evidence to support low bladder capacity as a marker of a distinct bladder-centric IC/BPS phenotype.

Pelvic floor muscle weakness: a risk factor for anterior vaginal wall prolapse recurrence.

INTRODUCTION AND HYPOTHESIS: Native tissue vaginal repairs are associated with relatively high levels of recurrence. Systematic reviews have noted that preoperative pelvic floor muscle strength was associated with increased risk of recurrence in the short term. METHODS: This is a retrospective review of patients who underwent a primary reconstructive surgery for anterior compartment vaginal prolapse between 2001 and 2015. Patients were divided into "absent," "weak" and "good" preoperative PFM strength (aPFM, wPFM and gPFM, respectively) based on a modified Oxford scale. Failure rates were determined by a composite of subjective and objective anatomic outcomes. Subjects who underwent re-operations or procedures for recurrent prolapse of the anterior compartment were considered failures. A p value < 0.05 was considered statistically significant. RESULTS: Two hundred ninety-nine patients were included. The aPFM (n = 36), wPFM (n = 115) and gPFM (n = 148) groups had similar descriptive statistics, except subjects in the aPFM and wPFM groups were significantly older than the gPFM group (p = 0.008). All groups underwent similar reconstructive surgeries. Average length of follow-up of 143.9 weeks (41 to 717 weeks) was similar among the three groups (p = 0.472). For the primary outcome of composite failure, aPFM had significantly more anterior vaginal wall recurrences than both the wPFM and gPFM groups, 13.89% vs. 3.48% and 4.05%, respectively (p = 0.033). CONCLUSIONS: Patients with preoperative absent pelvic floor muscle strength (nonfunctioning PFM) had a significantly higher anterior vaginal wall recurrence rate than those with weak or good pelvic floor muscle strength.

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.

Comparison of Methods to Identify Stress Urinary Incontinence in Women With Pelvic Organ Prolapse.

OBJECTIVE: The aim of the study was to compare which test is most sensitive in identifying stress urinary incontinence (SUI) in women with pelvic organ prolapse using urodynamics (UDS) as the criterion standard: cough stress test (CST) or pyridium pad test. METHODS: This was a prospective study of women with pelvic organ prolapse stage II or greater who desired surgical management for prolapse. Each patient underwent preoperative urinary testing: UDS, CST, and a 24-hour pyridium pad test. RESULTS: A total of 84 patients were analyzed. Using UDS as the criterion standard, both the CST and the pyridium pad test showed a fair agreement with UDS outcomes (κ = 0.27 for both tests). There was no statistically significant difference between the CST and the pyridium pad test, with estimated sensitivities of 34.4% versus 40.6% (P = 0.791), specificities of 90.4% versus 84.6% (P = 0.508). The pyridium pad test was found to have a statistically significant difference in identifying the subjective complaint of SUI (38.6%, P = 0.003) compared with other tests. Patients with occult incontinence were identified 42.5%, 17.5%, and 10% of the time during UDS, CST, and pyridium pad testing, respectively. CONCLUSION: Our data suggest that the sensitivities of the CST and pyridium pad test for stress incontinence and occult stress incontinence in patients with pelvic organ prolapse are low when compared with UDS as the criterion standard. Urodynamics has an important role in preoperative identification of occult SUI.

Robotic-assisted repair of pelvic organ prolapse: a scoping review of the literature.

The purpose of this article is to perform a scoping review of the medical literature regarding the efficacy, safety, and cost of robotic-assisted procedures for repair of pelvic organ prolapse in females. Sacrocolpopexy is the "gold standard" repair for apical prolapse for those who desire to maintain their sexual function, and minimally-invasive approaches offer similar efficacy with fewer risks than open techniques. The introduction of robotic technology has significantly impacted the field, converting what would have been a large number of open abdominal sacrocolpopexy (ASC) procedures to a minimally-invasive approach in the United States. Newer techniques such as nerve-sparing dissection at the sacral promontory, use of the iliopectineal ligaments and natural orifice vaginal sacrocolpopexy may improve patient outcomes. Prolapse recurrence is consistently noted in at least 10% of patients regardless of route of mesh placement. Ancillary factors including pre-operative prolapse stage, retention of the cervix, type of mesh implant, and genital hiatus (GH) size all adversely affect surgical efficacy, while trainees do not. Minimally-invasive apical repair procedures are suited to early recovery after surgery protocols but may not be appropriate for all patients. Studies evaluating longer-term outcomes of robotic sacrocolpopexies are needed to understand the relative risk/benefit ratio of this technique. With several emerging robotic platforms with improved features and a focus on decreasing costs, the future of robotics seems bright.

Free transverse rectus abdominis myocutaneous and deep inferior epigastric perforator flaps for breast reconstruction: a systematic review of flap complication rates and donor-site morbidity.

Free transverse rectus abdominis myocutaneous and deep inferior epigastric perforator flaps represent increasingly popular options for breast reconstruction. Although several retrospective, small-scale studies comparing these flaps have been published, most have failed to find a significant difference in flap complication rates or donor-site morbidity. We systematically reviewed the current literature, and subsequently pooled and analyzed data from included studies. Included studies reported flap complications and/or donor site morbidities for both flap types. Eight studies met the inclusionary criteria. For flap complications, there was a statistically significant difference between deep inferior epigastric perforator and free transverse rectus abdominis myocutaneous flaps in fat necrosis rates (25.5 +/- 0.49 vs. 11.3% +/- 0.41%, P < 0.001) and total necrosis rates (4.15 +/- 0.08 vs. 1.59% +/- 0.08%, P = 0.044). Partial necrosis rates were not statistically significant (3.54 +/- 0.07 vs. 1.60% +/- 0.07%, P = 0.057). For donor-site morbidity, there was no statistically significant difference in abdominal bulge (8.07 +/- 0.23 vs. 11.25% +/- 0.29%, P = 0.28). Multicenter, prospective studies are needed to further investigate differences between these flap options.

Robotic-assisted Sacrocolpopexy with versus without Concomitant Midurethral Sling: A 2-year Follow-up of Urinary Symptoms and Quality of Life.

OBJECTIVE: The objective of this study was to assess long-term postoperative urinary incontinence (UI) symptoms and quality of life (QOL) in patients after robotic-assisted sacrocolpopexy (RASC) with or without concomitant midurethral sling (MUS). MATERIALS AND METHODS: This is a cross-sectional survey of patients comparing long-term postoperative urinary symptoms and QOL measurements in women who underwent RASC with or without MUS. We included all patients from 2011 to 2014 who had RASC with or without MUS. All patients had preoperative urodynamic testing (UDS). Patients who demonstrated stress UI on UDS underwent MUS at the time of RASC. Urinary symptoms and QOL were assessed through the validated Urinary Distress Inventory-6 (UDI-6) and Incontinence Impact Questionnaire-7 (IIQ-7) patient questionnaires. RESULTS: Sixty-eight patients met inclusion criteria, 46 patients completed follow-up questionnaires, and were included in the final analysis. Average length of time to follow-up from surgery was 24 months (range: 6-36 months). A statistically significant difference in UDI-6 scores between the two groups (RASC vs. RASC + MUS) was observed. Median (25th and 75th percentiles) scores for UDI-6 were 22.92 (8.33 and 32.29, respectively) for the RASC group and 4.17 (0 and 13.54, respectively) for the RASC + MUS group (P = 0.0017). Median scores for IIQ-7 were 0 (0 and 29.73 for the 25th and 75th percentiles, respectively) for the RASC group and 0 (0 and 0, respectively) for the RASC + MUS group (P = 0.1691). CONCLUSION: Patients who underwent RASC + MUS scored significantly lower on the UDI-6, indicating fewer urinary distress symptoms. Although not statistically significant, patients in the RASC + MUS group had lower IIQ-7 scores, indicating less negative impact on QOL, compared to the RASC-only group.

Combination therapy accelerates diabetic wound closure.

BACKGROUND: Non-healing foot ulcers are the most common cause of non-traumatic amputation and hospitalization amongst diabetics in the developed world. Impaired wound neovascularization perpetuates a cycle of dysfunctional tissue repair and regeneration. Evidence implicates defective mobilization of marrow-derived progenitor cells (PCs) as a fundamental cause of impaired diabetic neovascularization. Currently, there are no FDA-approved therapies to address this defect. Here we report an endogenous PC strategy to improve diabetic wound neovascularization and closure through a combination therapy of AMD3100, which mobilizes marrow-derived PCs by competitively binding to the cell surface CXCR4 receptor, and PDGF-BB, which is a protein known to enhance cell growth, progenitor cell migration and angiogenesis. METHODS AND RESULTS: Wounded mice were assigned to 1 of 5 experimental arms (n = 8/arm): saline treated wild-type, saline treated diabetic, AMD3100 treated diabetic, PDGF-BB treated diabetic, and AMD3100/PDGF-BB treated diabetic. Circulating PC number and wound vascularity were analyzed for each group (n = 8/group). Cellular function was assessed in the presence of AMD3100. Using a validated preclinical model of type II diabetic wound healing, we show that AMD3100 therapy (10 mg/kg; i.p. daily) alone can rescue diabetes-specific defects in PC mobilization, but cannot restore normal wound neovascularization. Through further investigation, we demonstrate an acquired trafficking-defect within AMD3100-treated diabetic PCs that can be rescued by PDGF-BB (2 µg; topical) supplementation within the wound environment. Finally, we determine that combination therapy restores diabetic wound neovascularization and accelerates time to wound closure by 40%. CONCLUSIONS: Combination AMD3100 and PDGF-BB therapy synergistically improves BM PC mobilization and trafficking, resulting in significantly improved diabetic wound closure and neovascularization. The success of this endogenous, cell-based strategy to improve diabetic wound healing using FDA-approved therapies is inherently translatable.

Interval cranioplasty: comparison of current standards.

BACKGROUND: Although different cranioplasty storage methods are currently in use, no study has prospectively compared these methods. The authors compare freezing and subcutaneous storage methods in a rat model. METHODS: Trephine defects (10 mm) were created in 45 Sprague-Dawley rats. The cranial bone grafts were stored in an autologous subcutaneous pocket (n = 15), frozen at -80°C (n = 15), immediately analyzed (n = 12), or immediately replanted into the defect (n = 3). After 10 days of storage, the subcutaneous or frozen grafts were either replanted (subcutaneous, n = 3; frozen, n = 3) or analyzed (subcutaneous, n = 12; frozen, n = 12). Grafts underwent histologic analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, alkaline phosphatase assay, mechanical testing, and micro-computed tomographic imaging. RESULTS: After 10 days of storage, physiologic assays demonstrated a significant decrease in cellular functionality (e.g., alkaline phosphatase assay concentration: fresh, 18.8 ± 0.77 mM/mg; subcutaneous, 12.2 ± 0.63 mM/mg; frozen, 8.07 ± 1.1 mM/mg; p < 0.012 for all comparisons). Mechanical integrity (maximal load) of fresh grafts was greatest (fresh, 9.26 ± 0.29 N; subcutaneous, 6.27 ± 0.64 N; frozen, 4.65 ± 0.29 N; fresh compared with frozen, p < 0.001; fresh compared with subcutaneous, p = 0.006). Replantation of subcutaneously stored and frozen grafts resulted in limited bony union and considerable resorption after 12 weeks; in contrast, replanted fresh grafts demonstrated bony union and little resorption. CONCLUSIONS: Current preservation methods for interval cranioplasty do not maintain bone graft viability. Subcutaneous storage appears to provide a small advantage compared with freezing.

Scaffold-based rhBMP-2 therapy in a rat alveolar defect model: implications for human gingivoperiosteoplasty.

BACKGROUND: Primary alveolar cleft repair has a 41 to 73 percent success rate. Patients with persistent alveolar defects require secondary bone grafting. The authors investigated scaffold-based therapies designed to augment the success of alveolar repair. METHODS: Critical-size, 7 x 4 x 3-mm alveolar defects were created surgically in 60 Sprague-Dawley rats. Four scaffold treatment arms were tested: absorbable collagen sponge, absorbable collagen sponge plus recombinant human bone morphogenetic protein-2 (rhBMP-2), hydroxyapatite-tricalcium phosphate, hydroxyapatite-tricalcium phosphate plus rhBMP-2, and no scaffold. New bone formation was assessed radiomorphometrically and histomorphometrically at 4, 8, and 12 weeks. RESULTS: Radiomorphometrically, untreated animals formed 43 +/- 6 percent, 53 +/- 8 percent, and 48 +/- 3 percent new bone at 4, 8, and 12 weeks, respectively. Animals treated with absorbable collagen sponge formed 50 +/- 6 percent, 79 +/- 9 percent, and 69 +/- 7 percent new bone, respectively. Absorbable collagen sponge plus rhBMP-2-treated animals formed 49 +/- 2 percent, 71 +/- 6 percent, and 66 +/- 7 percent new bone, respectively. Hydroxyapatite-tricalcium phosphate treatment stimulated 69 +/- 12 percent, 86 +/- 3 percent (p < 0.05), and 87 +/- 14 percent new bone, respectively. Histomorphometry demonstrated an increase in bone formation in animals treated with hydroxyapatite-tricalcium phosphate plus rhBMP-2 (p < 0.05; 4 weeks) compared with empty scaffold. CONCLUSIONS: Radiomorphometrically, absorbable collagen sponge and hydroxyapatite-tricalcium phosphate scaffolds induced more bone formation than untreated controls. The rhBMP-2 added a small but significant histomorphometric osteogenic advantage to the hydroxyapatite-tricalcium phosphate scaffold.