How I Do It: EnPlace sacrospinous ligament fixation.

Pelvic organ prolapse (POP) is a common condition that significantly impairs a woman's quality of life.  Currently a range of interventions from non-surgical to surgical options exist, all with their unique advantages and disadvantages.  Among these, the EnPlace system stands out as a truly minimally invasive transvaginal percutaneous device designed to repair apical POP by bilaterally anchoring sutures to the sacrospinous ligaments.  Readers will familiarize themselves with the EnPlace, relevant historical studies, and the technique for EnPlace transvaginal percutaneous sacrospinous ligament fixation for hysteropexy or colposuspension.

Postoperative Activity Restrictions After Slings: A Randomized Controlled Trial.

IMPORTANCE: Restricting activity after midurethral slings is an unproven practice. OBJECTIVE: The objective of this study was to evaluate the effect of postoperative activity restriction on satisfaction and outcomes after slings. STUDY DESIGN: This was a multicenter, 2-arm, noninferiority randomized controlled trial. Patients aged 18-85 years undergoing treatment with a midurethral sling were randomized 1:1 to postoperative activity restriction or liberal activity. Restrictions included avoidance of strenuous exercise and heavy lifting. The liberal group was allowed to resume activity at their discretion. Our primary outcome was satisfaction with postoperative instruction at 2 weeks. Secondary outcomes included surgical failure, mesh exposure rates, and other adverse events. RESULTS: In total, 158 patients were randomized with 80 to the liberal group and 78 to the restricted group. At 2 weeks, 54 (80.6%) of patients in the liberal group and 48 (73.9%) of patients in the restricted group were satisfied. We found statistical evidence supporting the hypothesis that postoperative liberal activity instruction is noninferior to activity restriction with regard to patient satisfaction (P = 0.0281). There was no significant difference in strenuous activity at 2 weeks (P = 0.0824). The liberal group reported significantly more moderate activity at 2 weeks (P = 0.0384) and more strenuous activity at 6 weeks and 6 months (P = 0.0171, P = 0.0118, respectively). The rate of recurrent or persistent stress incontinence for liberal versus restricted groups was 18.52% versus 23.53% (P = 0.635). There were no statistically significant differences in complication rates. CONCLUSIONS: Postoperative liberal activity was noninferior to activity restriction with regard to patients' satisfaction. There was no evidence supporting a statistically significant association between postoperative instruction and negative surgical outcomes.

Does a Preoperative Bowel Regimen Change Time to Bowel Movement? A Randomized Clinical Trial.

IMPORTANCE: This study is important because it aimed to assess an intervention to decrease patient discomfort after a robotic sacral colpopexy. OBJECTIVE: Our primary outcome was to determine whether preoperative use of polyethylene glycol decreases time to first bowel movement postoperatively. Secondary outcomes include degree of pain with first bowel movement and stool consistency. STUDY DESIGN: This was a randomized controlled trial. The experimental group was assigned polyethylene glycol daily for 7 days before surgery and the control group was not. All patients received polyethylene glycol postoperatively. RESULTS: There was no statistically significant reduction in the time to first postoperative bowel movement when preoperative polyethylene glycol was used (mean [SD] in days for the control and experimental groups of 2.32 [0.99] and 1.96 [1.00], P = 0.21). There was a statistically significant reduction in pain levels with the first postoperative bowel movement in the experimental group (median [IQR] of 4 [2-5] vs 1 [0-2], P = 0.0007). Postoperative day 1 pain levels were also significantly lower in the experimental group (median [IQR] of 4 [3-6] vs 2 [0-4], P = 0.0484). In addition, patients had decreased average postoperative pain levels over 7 days with an estimated difference in the median pain levels of 1.88 units (95% confidence interval, 0.64-3.12; P = 0.0038). CONCLUSIONS: Preoperative administration of polyethylene glycol did not decrease time to first postoperative bowel movement. Patients in the experimental group exhibited less pain with their first postoperative bowel movement and had improved pain levels on postoperative day 1.

Evaluation of the histological and biomechanical properties of poly-4-hydroxybutyrate scaffold for pelvic organ prolapse, compared with polypropylene mesh in a rabbit model.

INTRODUCTION AND HYPOTHESIS: Poly-4-hydroxybutyrate (P4HB) is a biopolymer produced by Escherichia coli K12 bacteria. P4HB is fully resorbed in vivo by 18-24 months post-implantation. The aim of this study is to evaluate P4HB in the rabbit abdomen and vagina to determine that the biomechanical and histological properties are similar to the standard polypropylene mesh. Our hypothesis is that the histological and biomechanical properties of a fully absorbable graft will be similar to a lightweight polypropylene (PP) mesh when implanted in rabbit vagina and abdomen. METHODS: Sixteen (n = 16) female New Zealand White (retired breeder) rabbits were equally divided between two time points (3 and 9 months). A total of 17 rabbits were used owing to one death secondary to suspected cardiomyopathy. P4HB scaffold and PP mesh were subcutaneously and peri-vaginally implanted into the rabbit abdomen and vagina respectively. All rabbits had both posterior and anterior vaginal implants, and half of the rabbits had four abdominal implants in addition to the vaginal implants. The abdominal implants were 4.5 cm long × 1.5 cm wide whereas the vaginal implants were 1.5 cm long × 0.5 cm wide. At 3 and 9 months, gross necropsy was performed and samples were obtained, sectioned, stained and evaluated via histological analysis. Specimens were assessed for host inflammatory response, neovascularization, elastin content, and collagen deposition/maturation. Specimens were also biomechanically evaluated via uniaxial tensile test to determine the stiffness, ultimate tensile strength and load at ultimate tensile strength of the device/tissue composite. RESULTS: No abdominal mesh exposures were noted. A comparable number of asymptomatic partial vaginal exposures were observed at 3 months (P4HB: n = 3; PP: n = 2) and 9 months (P4HB: n = 3; PP: n = 2) respectively. Histological analysis of specimens showed comparable results in the P4HB and PP groups at 3 and 9 months post-implantation. Although no acute inflammation was seen, chronic inflammation was demonstrated in all specimens. Elastic fibers were present in the 3-month vaginal PP and P4HB specimens, but were not seen again. There was an increase in type I/III collagen noted over time. Biomechanical evaluation of the vaginal mesh tissue complex showed ultimate tensile strength was not significantly different between P4HB and PP groups at 3 (P = 0.625) and 9 months (P = 0.250) respectively. CONCLUSIONS: P4HB scaffold may represent a fully absorbable alternative to permanent mesh for pelvic organ prolapse (POP) repair.

Inflammatory Urinary Cytokine Expression and Quality of Life in Patients With Overactive Bladder.

OBJECTIVE: The aims of this study were to analyze levels of selected inflammatory urinary cytokines/chemokines in subjects with overactive bladder (OAB) and to determine if cytokine/chemokine levels correlate with quality of life and symptom distress. METHODS: This prospective, case-control pilot analysis included 23 women with OAB and 22 control subjects. Overactive bladder subjects were enrolled if they had symptoms of urinary frequency, urgency, or urge incontinence for more than 3 months and urodynamic evidence of detrusor overactivity. Control subjects denied urinary symptoms. Subjects and control subjects were excluded if they had known inflammatory bladder or systemic conditions, cystitis, stones, or recent anticholinergic use. Urine samples were collected from each subject and control. Subjects filled out the Incontinence Quality of Life Questionnaire and the Urinary Distress Inventory Questionnaire 6. Cytokine/chemokine levels were determined using the multiplexed Meso Scale Discovery Platform and were corrected for urinary creatinine concentrations. Statistical analysis comparing cytokine/chemokine levels was performed using the Mann-Whitney U test; relationships between cytokine/chemokine and questionnaire scores were calculated with Spearman correlation coefficient. RESULTS: Subjects with OAB had significantly lower urinary interleukin 10 (IL-10), IL-12-p70, and IL-13 levels compared with control subjects. Interleukin 1 correlated with worsening symptom distress on Urinary Distress Inventory Questionnaire 6. CONCLUSIONS: To our knowledge, this is at present the only study correlating inflammatory cytokine/chemokine levels in women with OAB with quality of life and distress. Interleukin 1 signified worsening distress, whereas IL-10, IL-12p70, and IL-13 were the only cytokines found at different levels in subjects. Our findings support a larger study in order to evaluate the value of urinary cytokines/chemokines as potential biomarkers.

The prevalence of microscopic hematuria in a cohort of women with pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: In 2012, the American Urological Association (AUA) revised its guidelines for microscopic hematuria (MH). We hypothesize that the prevalence of MH is greater in women with pelvic organ prolapse than in the general population. METHODS: All patients presenting to an outpatient urogynecological center with prolapse between January 2008 and December 2011 were reviewed. Exclusion criteria included: pregnancy, presence of gross hematuria, menses, or urological pathology. MH was defined as ≥3 red blood cells per high power field on one urinalysis specimen with a negative urine culture, and the prevalence of MH was calculated. Statistical analysis was performed. RESULTS: One thousand and forty women with pelvic organ prolapse were included in the analysis. Mean age was 64.1 years (range 20 to 96) and mean parity was 2.7 (range 0 to 12). Two hundred and nine out of 1,040 met the criteria for MH. No cases of urological malignancy were diagnosed in patients who underwent further workup. One hundred and ninety-seven patients with MH (93.4 %) had cystoceles on examination. CONCLUSIONS: This is the largest study to investigate MH in women with prolapse based on the new guidelines. The prevalence of MH was 20.1 % in our study population. Cystoscopy, renal function testing, and CT urography are now recommended after one positive urinalysis, regardless of gender or the presence of prolapse. Owing to the low incidence of urological malignancy detected as well as the increased prevalence of MH found in women with prolapse, specific guidelines for the management of MH in this population are needed.

Sacral nerve stimulation reduces elevated urinary nerve growth factor levels in women with symptomatic detrusor overactivity.

OBJECTIVES: To investigate changes in urinary nerve growth factor (uNGF) in women with symptomatic detrusor overactivity (DO) following peripheral nerve evaluation (PNE) for sacral neuromodulation vs controls. STUDY DESIGN: There were 23 subjects with overactive bladder symptoms and DO who failed management with anticholinergics and 22 controls consented to participate in this prospective pilot study. Urine specimens were collected from controls at baseline for evaluation of uNGF and creatinine. Subjects were evaluated at baseline and 5 days after a trial of sacral nerve stimulation referred to as a PNE. Each visit included urine collection for uNGF and, Incontinence Quality of Life Questionnaire, Urinary Distress Inventory Questionnaire, postvoid residual volume, and a 3-day voiding diary. uNGF levels were measured by enzyme-linked immunosorbent assay and expressed as uNGF pg/creatinine mg. RESULTS: Subjects with DO had significantly higher baseline uNGF levels (corrected for creatinine) compared with controls (19.82 pg/mg vs 7.88 pg/mg, P < .002). Seventeen DO subjects underwent PNE and were evaluated at the end of the testing period. There was a significant improvement in quality of life scores for subjects after PNE compared with baseline (Urinary Distress Inventory Questionnaire: 7.0 vs 13.7, P < .001; Incontinence Quality of Life Questionnaire: 87.3 vs 52.8, P < .0001). Concordantly, uNGF levels significantly decreased from 17.23 pg/mg to 9.24 pg/mg (P < .02) after PNE. CONCLUSION: uNGF levels decrease with symptomatic response in DO subjects undergoing PNE. DO subjects had significantly higher uNGF at baseline vs controls, and uNGF levels significantly decreased after only 5 days of sacral nerve stimulation. These findings support a larger study to validate the use of uNGF as an objective tool to assess therapeutic outcome in patients undergoing PNE for sacral neuromodulation.

Quantitative determination of the topological propensities of amyloidogenic peptides.

One of the interesting puzzles of amyloid beta-peptide of Alzheimer's disease (Abeta) is that it appears to polymerize into amyloid fibrils in a parallel beta sheet topology, while smaller subsets of the peptide produce anti-parallel beta sheets. In order to target potential weak points of amyloid fibrils in a rational drug design effort, it would be helpful to understand the forces that drive this change. We have designed two peptides CHQKLVFFAEDYNGKDEAFFVLKQHW and CHQKLVFFAEDYNGKHQKLVFFAEDW that join the significant amyloidogenic Abeta (14-23) sequence HQKLVFFAED in parallel and anti-parallel topologies, respectively. (Here, the word "parallel" refers only to residue sequence and not backbone topology). The N-termini of the hairpins were labeled with the fluorescent dye 5-((((2-iodoacetyl)amino)ethyl)amino)naphthalene-1-sulfonic acid (IAEDANS), forming a fluorescence energy transfer donor-acceptor pair with the C-terminus tryptophan. Circular dichroism results show that the anti-parallel hairpin adopts a beta-sheet conformation, while the parallel hairpin is disordered. Fluorescent Resonance Energy Transfer (FRET) results show that the distance between the donor and the acceptor is significantly shorter in the anti-parallel topology than in the parallel topology. The fluorescence intensity of anti-parallel hairpin also displays a linear concentration dependence, indicating that the FRET observed in the anti-parallel hairpin is from intra-molecular interactions. The results thus provide a quantitative estimate of the relative topological propensities of amyloidogenic peptides. Our FRET and CD results show that beta sheets involving the essential Abeta (14-23) fragment, strongly prefer the anti-parallel topology. Moreover, we provide a quantitative estimate of the relative preference for these two topologies. Such analysis can be repeated for larger subsets of Abeta to determine quantitatively the relative degree of preference for parallel/anti-parallel topologies in given fragments of Abeta.