Pelvic floor symptoms among premenopausal women with pelvic organ prolapse in the Democratic Republic of the Congo.

INTRODUCTION AND HYPOTHESIS: Most of the literature on pelvic organ prolapse (POP) has been generated from postmenopausal patients in high-income countries. In the Democratic Republic of the Congo (DRC), a significant proportion of patients who present for surgical management of POP are premenopausal. Little is known about the impact of POP on pelvic floor symptoms in this population. The objective was to describe pelvic floor symptoms and sexual function among premenopausal patients presenting for POP surgery in DRC. METHODS: We performed a prospective cohort study of symptomatic premenopausal patients undergoing fertility-sparing POP surgery at a large referral hospital in the DRC. Pelvic floor symptoms were evaluated with the Pelvic Floor Distress Inventory Questionnaire and sexual function with the Pelvic organ prolapse/urinary Incontinence Sexual Questionnaire. Data are presented as means with standard deviations or counts with percentages. RESULTS: A total of 107 patients were recruited between April 2019 and December 2021. All had either stage III (95.3%) or stage IV (4.7%) prolapse. Ages were 34.2 ± 6.7 years; 78.5% were married. A majority of patients experienced low abdominal pain (82.2%), heaviness or dullness (95.3%), and bulging or protrusion of the prolapse (92.5%). Almost two-thirds of patients reported no longer being sexually active, and 80% stated that they were not sexually active because of POP. Of the 37 sexually active patients (34.6%), nearly all reported significant sexual impairment because of the prolapse, with only 4 reporting no sexual impairment. CONCLUSIONS: This study represents one of the largest prospective series of patients with premenopausal POP. Our results highlight the severity of pelvic floor symptoms and the negative effects on sexual function among this patient population with POP.

A feasibility study of three-dimensional ultrasound imaging of the vagina under distension.

BACKGROUND: The distension properties of the vagina are critical to its function including support of surrounding organs, childbirth, and intercourse. It could be altered by many pathophysiological processes like pregnancy, radiotherapy, and reconstruction surgery. However, there are no clinically available diagnostic tools capable of quantifying the distension properties of the vagina. PURPOSE: A proof-of-concept study was designed to assess the feasibility of a novel three-dimensional (3D) ultrasound imaging technique that allows quantitative evaluation of the vagina under distension. METHODS: Patients with symptomatic pelvic organ prolapse (POP) were recruited for the study. An ultrathin, oversized bag was inserted into the vagina and filled with water using a modified urodynamics system. The instilled water volume and intravaginal pressure were continuously recorded. At maximum vaginal capacity, 3D transintroital ultrasound of the distended vagina and surrounding pelvic structures was performed. Exams were performed in duplicate for each patient, two hours apart (round A and round B). Following the development of a 3D surface model of the distended vagina from each scan, several measurements were obtained, including cross-sectional area, anteroposterior (AP) length and lateral width in the plane of minimum hiatal dimensions (PMHD), AP and lateral diameter at the pubic symphysis (PS) level, maximum and minimum diameter, and maximum vertical length. To assess repeatability between measurements in two rounds, the coefficient of variation (CV) and the intraclass correlation coefficient (ICC) were calculated for each measurement. Correlations between physical measurements including the pelvic organ prolapse quantification (POP-Q) system and vaginal diameter measurements, and obtained metrics were also assessed. RESULTS: Sixteen patients with POP (average age 69 years) completed both rounds of imaging. There was sufficient echogenicity on 3D transintroital ultrasound of the distended vaginal wall to establish boundaries for 3D surface models of the vagina. Overall, all metrics had good or excellent reliability (ICC = 0.77-0.93, p < 0.05; CV = 3%-18%) except maximum diameter, which demonstrated only moderate reliability (ICC = 0.67, p = 0.092). Strong correlations were found between physical exam measurements including D point of POP-Q, introitus diameter and lateral diameter at apex, and maximum vaginal capacity, maximum vertical length, lateral diameter at PS, minimum diameter, and distended PMHD measurements. The results demonstrated that this system could generate 3D models of the shape of the distended vagina and provide multiple metrics that could be reliably calculated from automated analyses of the models. CONCLUSIONS: A novel system for evaluation of the distension properties of the vagina was developed and preliminary evaluation was performed. This system may represent a technique for evaluation of the biomechanical and structural properties of the vagina.

Patient-Specific Pessaries for Pelvic Organ Prolapse Using Three-Dimensional Printing: A Pilot Study.

IMPORTANCE: Vaginal pessaries are an effective nonsurgical treatment for pelvic organ prolapse (POP) when properly fitted. However, pessary fitting and use are often unsuccessful or imperfect. OBJECTIVE: The objective of this study was to assess the feasibility of using patient-specific pessaries fabricated from three-dimensional (3D)-printed molds to improve POP symptoms and increase overall satisfaction of pessary treatment in patients using standard vaginal pessaries. STUDY DESIGN: Patients undergoing POP treatment with standard vaginal pessaries were enrolled in this pilot prospective study. Patient-specific pessaries were designed and fabricated for each patient using patient input, physician input, and anatomic measurements from clinical assessment. Pessary fabrication involved injection of biocompatible liquid silicone rubber into 3D-printed molds followed by a biocompatible silicone coating. Pelvic organ prolapse symptomatic distress and pessary treatment satisfaction were evaluated before and after a 3-week patient-specific pessary home trial using the validated Pelvic Organ Prolapse Distress Inventory-6 form and a visual analog scale, respectively. RESULTS: Eight women were included in this study. Changing from standard pessary to patient-specific pessary treatment was associated with an improvement in prolapse symptoms on the Pelvic Organ Prolapse Distress Inventory-6 (median change, -3.5; interquartile range, -5 to -2.5; P = 0.02) and an increase in overall pessary satisfaction on a visual analog scale (median change, +2.0; interquartile range, +1.0 to +3.0; P = 0.02). All patients reported either an improvement or no change in pessary ease of use, comfort, and the feeling of support provided by the pessary. CONCLUSION: Patient-specific vaginal pessaries are a promising alternative to standard pessaries for alleviating POP symptoms and improving patient satisfaction with pessary use.

Commercially Available Home Pelvic Training Devices for the Treatment of Pelvic Floor Disorders: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess the clinical efficacy of commercially available pelvic muscle training devices on the treatment of pelvic floor disorders. DATA SOURCES: We searched MEDLINE, Web of Science, and ClinicalTrials.gov through April 2020. We included observational cohort studies and randomized trials. Case reports, case series, and conference poster presentations were excluded. Studies using vaginal weights or cones and those conducted in the peripartum periods were also excluded. TABULATION, INTEGRATION, AND RESULTS: A total of 294 studies were screened. Twenty-six studies were included in the qualitative analysis, and 15 studies were eligible for meta-analyses. Study characteristics and quality were recorded for each study. Meta-analysis showed a large positive effect of commercially available pelvic floor training devices on pelvic floor muscle strength by both objective and subjective measures. Meta-analysis of objective measures showed a reduction of 1.2 pads per day (P<.01), 1.3 incontinence episodes per day, (P<.01) and 11 g on 24-hour pad test (P<.01). Meta-analysis of subjective measures showed a reduction in UDI-6 (Urogenital Distress Inventory, Short Form) scores by 25.1 points (P<.01) and in IIQ-7 scores (Incontinence Impact Questionnaire, Short Form) by 14.1 points (P=.01). There was an increase in I-QOL (Incontinence Quality of Life) scores by 16.8 points (P<.01). The minimal important difference was met for the UDI-6 and I-QOL but not for the IIQ-7. We were unable to perform meta-analysis to evaluate whether pelvic floor training devices are as effective as traditional supervised pelvic floor physical therapy. CONCLUSION: Commercially available home pelvic floor training devices are effective in increasing strength of pelvic floor muscles and in the treatment of pelvic floor disorders.

Surgical management of pelvic organ prolapse in a high-volume resource-limited setting.

OBJECTIVE: To describe the care pathway of patients with pelvic organ prolapse in a high-volume resource-limited setting and characterize patients undergoing surgery. METHODS: The patient care pathway at a large referral hospital in eastern Democratic Republic of Congo was determined through interviews with key personnel. Patients with apical prolapse (with or without anterior/posterior prolapse) who underwent surgery between January and December 2018 were included. Demographics and outcomes were characterized. Data were presented as means (standard deviation [SD]), medians (interquartile range), or number (percentages). RESULTS: A holistic care model was described. During the study period, 772 patients underwent prolapse repairs, 235 met inclusion criteria. Mean age was 55 (±14) years, and 75% (176/235) were postmenopausal. Median parity was 7 (5-9). A majority (56%, 131/233) had body mass index <18.5 (calculated as weight in kilograms divided by the square of height in meters). Most were farmers (77%, 182/235) and had no formal education (76%, 178/235). Postmenopausal patients underwent hysterectomy, whereas premenopausal patients were treated with uterine-preserving techniques. Most repairs were performed vaginally (96%, 225/235), and 40% (94/234) had concurrent multicompartment repairs. Most common complications were hemorrhage (4%, 9/235, intraoperative) and urinary tract infection (5%, 11/235, postoperative). CONCLUSION: High-volume surgical services for treating prolapse can be integrated into existing healthcare delivery models. Our demographic of patients differs from studies in high-income countries. The degree to which these studies can be generalized to patients in settings similar to ours represents an opportunity for further research.

Management of Intracranial Hemorrhage in Patients with a Left Ventricular Assist Device: A Systematic Review and Meta-Analysis.

BACKGROUND: Intracranial hemorrhage (ICH) has been reported to occur in up to 23% of patients with left ventricular assist devices (LVADs). Currently, limited data exists to guide neurosurgical management strategies to optimize outcomes in patients with an LVAD who develop ICH. METHODS: A systematic review and meta-analysis of the literature was performed to evaluate the mortality rate in these patients following medical and/or surgical management and to evaluate antithrombotic reversal and resumption strategies after hemorrhage. RESULTS: 17 studies reporting on 3869 LVAD patients and 545 intracranial hemorrhages spanning investigative periods from 1996 to 2019 were included. The rate of ICH in LVAD patients was 10.6% (411/3869) with 58.6% (231/394) being intraparenchymal hemorrhage (IPH), 23.6% (93/394) subarachnoid hemorrhage (SAH), and 15.5% (61/394) subdural hemorrhage (SDH). Total mortality rates for surgical management 65.6% (40/61) differed from medical management at 45.2% (109/241). There was an increased relative risk of mortality (RR=1.45, 95% CI: 1.10-1.91, p = 0.01) for ICH patients undergoing surgical intervention. The hemorrhage subtype most frequently managed with anticoagulation reversal was IPH 81.8% (63/77), followed by SDH 52.2% (12/23), and SAH 39.1% (18/46). Mean number of days until antithrombotic resumption ranged from 6 to 10.5 days. CONCLUSION: Outcomes remain poor, specifically for those undergoing surgery. As experience with this population increases, prospective studies are warranted to contribute to management and prognostication .

Role of lysyl oxidase like 1 in regulation of postpartum connective tissue metabolism in the mouse vagina†.

Pelvic organ prolapse (POP) in lysyl oxidase like-1 knockout (Loxl1 KO) mice occurs primarily in parous mice and is rare in nulliparous mice. We determined the effect of Loxl1 deficiency on postpartum regulation of connective tissue metabolism genes and degradative enzyme activity in the vagina at 20 days gestation or 4 h, 48 h, 7 days, 15 days, 25 days, 7 weeks, or 12 weeks postpartum. Nulliparous Loxl1 KO and wildtype (WT) mice aged 11, 18, or 23 weeks were controls. Gene expression and enzyme activity were assessed using real-time quantitative reverse transcription PCR and fluorescein conjugated gelatin zymography, respectively. Parity, but not aging, had a significant influence on gene expression both with time postpartum and between KO and WT mice. Mmp2, Timp1, Timp2, Timp3, Timp4, Col1a1, Col3a1, Acta2, and Bmp1 were differentially expressed between KO and WT mice. Correlational analysis of gene-gene pairs revealed 10 significant differences between parous KO and WT groups, 5 of which were due to lack of co-expression of Bmp1 in KO mice. The overall enzyme activity that could be attributed to MMPs was significantly higher in WT compared to KO mice both 25 days and 12 weeks postpartum, and MMP activity was significantly lower 15 days and 25 days postpartum compared to KO nulliparous controls, but not WT. These findings suggest that Loxl1 deficiency combined with parity has a significant impact on postpartum regulation of connective tissue metabolism, particularly as it relates to co-expression of Bmp1 and altered proteolytic activity.

The Ghana PrenaBelt trial: a double-blind, sham-controlled, randomised clinical trial to evaluate the effect of maternal positional therapy during third-trimester sleep on birth weight.

OBJECTIVE: To evaluate the effect, on birth weight and birth weight centile, of use of the PrenaBelt, a maternal positional therapy device, during sleep in the home setting throughout the third trimester of pregnancy. DESIGN: A double-blind, sham-controlled, randomised clinical trial. SETTING: Conducted from September 2015 to May 2016, at a single, tertiary-level centre in Accra, Ghana. PARTICIPANTS: Two-hundred participants entered the study. One-hundred-eighty-one participants completed the study. Participants were women, 18 to 35 years of age, with low-risk, singleton, pregnancies in their third-trimester, with body mass index <35 kg/m2 at the first antenatal appointment for the index pregnancy and without known foetal abnormalities, pregnancy complications or medical conditions complicating sleep. INTERVENTIONS: Participants were randomised by computer-generated, one-to-one, simple randomisation to receive either the PrenaBelt or sham-PrenaBelt. Participants were instructed to wear their assigned device to sleep every night for the remainder of their pregnancy (approximately 12 weeks in total) and were provided a sleep diary to track their use. Allocation concealment was by unmarked, security-tinted, sealed envelopes. Participants and the outcomes assessor were blinded to allocation. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were birth weight and birth weight centile. Secondary outcomes included adherence to using the assigned device nightly, sleeping position, pregnancy outcomes and feedback from participants and maternity personnel. RESULTS: One-hundred-sixty-seven participants were included in the primary analysis. The adherence to using the assigned device nightly was 56%. The mean ±SD birth weight in the PrenaBelt group (n=83) was 3191g±483 and in the sham-PrenaBelt group (n=84) was 3081g±484 (difference 110 g, 95% CI -38 to 258, p=0.14). The median (IQR) customised birth weight centile in the PrenaBelt group was 43% (18 to 67) and in the sham-PrenaBelt group was 31% (14 to 58) (difference 7%, 95% CI -2 to 17, p=0.11). CONCLUSIONS: The PrenaBelt did not have a statistically significant effect on birth weight or birth weight centile in comparison to the sham-PrenaBelt. TRIAL REGISTRATION NUMBER: NCT02379728.

Modifying Maternal Sleep Position in Late Pregnancy Through Positional Therapy: A Feasibility Study.

STUDY OBJECTIVES: To test whether a customized positional therapy device, PrenaBelt, would reduce time spent sleeping supine and evaluate any change in maternal or fetal parameters, in a group of healthy pregnant women in the third trimester of pregnancy. METHODS: Participants underwent an in-home, overnight sleep study during late pregnancy (32-38 weeks). Participants were observed over 2 nights: 1 night when the PrenaBelt was not worn (nonintervention or control) and 1 night when it was (intervention). The intervention night was randomly allocated, and the study nights were consecutive. On the control night, participants were filmed using a night-capable (infrared) video camera, maternal sleep was measured by the Watch-PAT200, and the fetus was continuously monitored using the Monica AN24. On the intervention night, video, maternal, and fetal monitoring were repeated with the addition of the mother wearing the PrenaBelt. RESULTS: A total of 25 healthy pregnant women were studied. Four had missing data for the Watch-PAT or Monica, and eight had missing or disrupted video data. Video-determined time in bed was not significantly different during intervention and control nights (P = .196, r = -.23). Median time spent supine during the intervention night was reduced from 48.3 minutes, to 28.5 minutes during the control night (P = .064, r = -.33). The difference in the proportion of time spent supine was significant (P = .039). There was no significant difference in objectively estimated sleep time (P = .651, r = -.07). Improvement was observed in both maternal and fetal parameters during the intervention night with an increase in median minimum maternal oxygen saturations (control = 91.6%, intervention = 92.4%, P = .006, r = -.42), fewer maternal oxygen desaturations (control = 7.1, intervention = 5.9, P = .095, r = -.26), and fewer fetal heart rate decelerations (control = 14.0, intervention = 10.4, P = .045, r = -.31) compared to the control night. CONCLUSIONS: Results provide preliminary evidence that an intervention to reduce supine sleep in late pregnancy may provide maternal and fetal health benefits, with minimal effect on maternal perception of sleep quality and objectively estimated sleep time. Further research to explore relationships between objectively determined maternal sleep position, maternal respiratory indices, and fetal well-being is warranted.

Modifying maternal sleep position in the third trimester of pregnancy with positional therapy: a randomised pilot trial.

OBJECTIVE: To evaluate whether the percentage of time spent supine during sleep in the third trimester of pregnancy could be reduced using a positional therapy device (PrenaBelt) compared with a sham device. DESIGN: A double-blind, randomised, sham-controlled, cross-over pilot trial. SETTING: Conducted between March 2016 and January 2017, at a single, tertiary-level centre in Canada. PARTICIPANTS: 23 participants entered the study. 20 participants completed the study. Participants were low-risk, singleton, third-trimester pregnant women aged 18 years and older with body mass index <35 kg/m2 at the first antenatal appointment for the index pregnancy and without known fetal abnormalities, pregnancy complications or medical conditions complicating sleep. INTERVENTIONS: A two-night, polysomnography study in a sleep laboratory. Participants were randomised by computer-generated, one-to-one, simple randomisation to receive either a PrenaBelt or a sham-PrenaBelt on the first night and were crossed over to the alternate device on the second night. Allocation concealment was by unmarked, security-tinted, sealed envelopes. Participants, the recruiter and personnel involved in setting up, conducting, scoring and interpreting the polysomnogram were blinded to allocation. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the percentage of time spent supine during sleep. Secondary outcomes included maternal sleep architecture, respiration, self-reported sleep position and feedback. RESULTS: The median percentage of sleep time supine was reduced from 16.4% on the sham night to 3.5% on the PrenaBelt night (pseudomedian=5.8, p=0.03). We were unable to demonstrate differences in sleep architecture or respiration. Participants underestimated the time they spent sleeping supine by 7.0%, and six (30%) participants indicated they would make changes to the PrenaBelt. There were no harms in this study. CONCLUSIONS: This study demonstrates that the percentage of sleep time supine during late pregnancy can be significantly reduced via positional therapy. TRIAL REGISTRATION NUMBER: NCT02377817; Results.

Natural history of pelvic organ prolapse in symptomatic patients actively seeking treatment.

INTRODUCTION AND HYPOTHESIS: At our institution many symptomatic patients must wait months or years for surgery. Our aim was to determine the rates of clinically significant pelvic organ prolapse (POP) progression and identify risk factors associated with POP progression. METHODS: Data from a prospectively maintained database of POP patients evaluated between 2008 and 2013 were analyzed. Women with symptomatic POP and two or more POP-Q examinations prior to surgery were included. POP progression was defined as having any of the POP-Q points Aa, Ba, C, D, Ap or Bp above the hymen at the baseline examination and at or below the hymen at the follow-up examination. Multivariable logistic analysis was preformed and the results are presented as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Of consecutive patients evaluated between July 2008 and June 2013, 388 met the inclusion criteria and were included. The median time between the POP-Q examinations was 9.9 months (IQR 7.8 to 13.8 months). The POP progression rate was 29.1% (95% CI 24.6-33.6%). Predictors of progression included age (OR 1.7, 95% CI 1.01-2.87) and the baseline status of points Ba, C, Bp and gH (OR 1.91, 95% CI 1.01-3.62; OR 0.53, 95% CI 0.3-0.94; OR 0.54, 95% CI 0.32-0.93; OR 2.15, 95% CI 1.13-4.1; respectively). POP-Q point correlations showed that anterior and posterior compartment points evolve with apical compartment points and gH evolves with both the anterior compartment and the apex. CONCLUSIONS: Up to 29.1% of symptomatic patients with POP showed clinically significant progression over a median follow-up of 9.9 months. The likelihood of progression was not significantly associated with time. Those ≥60 years of age as well as those with point Ba ≥4 cm or gH ≥5 cm at baseline were at increased risk of POP progression.

Surgeons' views on sling tensioning during surgery for female stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Little is known regarding the use of various techniques for sling tensioning. Our objective was to determine which techniques are most commonly used by surgeons and surgeons' views on sling tensioning. METHODS: An Internet-based survey designed to assess the use of various tensioning evaluation methods, different sling tensioning techniques, and views and beliefs regarding the importance of tensioning was sent to members of major sub-specialty professional organizations. The responses were analyzed using descriptive statistics, and univariate and multivariate logistic analyses were performed to assess the effect of various surgeon characteristics on operative techniques. RESULTS: A total of 596 surgeons (63% gynecologists, 37% urologists) from 56 different countries were included in the analysis. Over 30% of respondents reported performing >50 sling operations/year. Use of objective intraoperative tension evaluation methods was 15.6, 7.8, and 1.9% for intraoperative stress tests, cystoscopic evaluation of urethral coaptation, or Q-tip tests respectively. Sixty-three percent indicated that they tension retropubic transvaginal tape (RP) and transobturator tape (TOT) slings similarly, whereas 26.2% place more tension on TOT than RP slings and 10.4% place more tension on RP than TOT slings. Those with fellowship training were 66% more likely to utilize leak point pressure results to inform the degree of tensioning (OR 1.66, CI 1.04-2.66). CONCLUSIONS: Our results indicate that there is a wide degree of variation in technique among surgeons. Prospective studies assessing the utility of various techniques could provide more evidence-based approaches to midurethral sling surgery and potentially improve quality and patient outcomes.

Effect of Pregnancy and Delivery on Cytokine Expression in a Mouse Model of Pelvic Organ Prolapse.

OBJECTIVES: The aim of this study was to determine the effect of pregnancy and delivery mode on cytokine expression in the pelvic organs and serum of lysyl oxidase like-1 knockout (LOXL1 KO) mice, which develop pelvic organ prolapse after delivery. METHODS: Bladder, urethra, vagina, rectum, and blood were harvested from female LOXL1 KO mice during pregnancy, after vaginal or cesarean delivery, and from sham cesarean and unmanipulated controls. Pelvic organs and blood were also harvested from pregnant and vaginally delivered wild-type (WT) mice and from unmanipulated female virgin WT controls. Specimens were assessed using quantitative real-time reverse transcription polymerase chain reaction and/or enzyme-linked immunosorbent assay. RESULTS: Both CXCL12 and CCL7 mRNA were significantly up-regulated in the vagina, urethra, bladder, and rectum of pregnant LOXL1 KO mice compared with pregnant WT mice, suggesting systemic dysregulation of both of these cytokines in LOXL1 KO mice as a response to pregnancy.The differences in cytokine expression between LOXL1 KO and WT mice in pregnancy persisted after vaginal delivery. CCL7 gene expression increases faster and to a greater extent in LOXL1 KO mice, translating to longer lasting increases in CCL7 in serum of LOXL1 KO mice after vaginal delivery, compared with pregnant mice. CONCLUSIONS: Lysyl oxidase like-1 KO mice have an increased cytokine response to pregnancy perhaps because they are less able to reform and re-cross-link stretched elastin to accommodate pups, and this resultant tissue stretches during pregnancy. The up-regulation of CCL7 after delivery could provide an indicator of level of childbirth injury, to which the urethra and vagina seem to be particularly vulnerable.

Transcriptional Regulation of Connective Tissue Metabolism Genes in Women With Pelvic Organ Prolapse.

OBJECTIVE: The aim of this study was to compare differences in expressions and relationships between key genes involved in extracellular matrix metabolism and tissue cellularity in women with and without pelvic organ prolapse (POP). METHODS: A total of 80 biopsies (anterior cuff, posterior cuff, and/or leading edge) were obtained from 30 women: n = 10 premenopausal without POP (controls), n = 10 premenopausal with POP, and n = 10 postmenopausal with POP. Quantitative reverse-transcriptase polymerase chain reaction was used to assess gene expression of bone morphogenetic protein 1 (BMP1), collagen types I (COL1) and III (COL3), relaxin family peptide receptor 1 (RXFP1), matrix metallopeptidase 2, and TIMP metallopeptidase inhibitors 2 and 3. Hematoxylin and eosin staining was used to assess cellularity of the connective tissue layer. Kruskal-Wallis test, Mann-Whitney U test, Pearson correlation, or linear regression analyses were used, as appropriate. RESULTS: Bone morphogenetic protein 1 expression was significantly up-regulated in patients with POP compared with controls. Bone morphogenetic protein 1 expression was correlated with COL1 expression in all groups but only correlated with TIMP metallopeptidase inhibitor 3 expression in controls. Similarly, COL3 expression was correlated with RXFP1 expression in women with POP but not in controls. The degree of dependence (slope of the regression line) between COL1 and COL3 expressions was significantly elevated in premenopausal women with POP compared with the other 2 groups. The slopes between COL1-COL3, COL3-matrix metallopeptidase 2, COL1-RXFP1, and COL3-RXFP1 expressions were significantly lower in postmenopausal women compared with premenopausal women with POP. No differences were found in overall tissue cellularity. CONCLUSIONS: Bone morphogenetic protein 1 expression may play a significant role in the pathophysiology of POP. The finding that BMP1 expression was correlated with COL1 expression in all groups suggests a conserved association between BMP1 and collagen synthesis in the vaginal wall. The elevated slope between COL1 and COL3 expressions may be associated with early (premenopausal) development of POP. The expression of RXFP1 in postmenopausal women and its altered intergene regulation suggests a role for RXFP1 in connective tissue metabolism outside pregnancy.

Differential regulation of NSC phenotype and genotype by chronically activated microglia within cocultures.

Under disease or injury conditions in the central nervous system (CNS), activated microglia release cytokines and chemokines to modulate the microenvironment and influence tissue remodeling. To exploit the full potential of neural stem cell (NSC) transplantation approaches, a permissive microenvironment needs to be created for their survival, homing and differentiation. To investigate the role of chronically activated microglia in the fate of NSCs, spontaneously immortalized murine microglial cells (SIM-A9) were cocultured with embryonic murine cortical NSCs on 2D substrates or within 3D gels. Standalone NSC cultures served as controls. Cytokines and chemokines released by NSCs and SIM-A9 cells in standalone and cocultures were quantified. Coculturing with SIM-A9 cells suppressed NSC viability, neurite outgrowth, neural differentiation and TUJ1 gene expression, and promoted glia formation in both 2D and 3D cultures, over a 10-day period. The seven most-abundantly released analytes by microglia (MCP-1, MIP2, G-CSF, MIP-1α, MIP-1ß, TNF-α, IL-6) were tested for their individual effects on NSCs, to investigate if the outcomes in cocultures were due to the synergistic effects of analytes or the influence of any individual analyte. All the seven analytes significantly suppressed cell survival compared to controls, but exposure to MIP-1ß, IL-6, or MCP-1 enhanced neurite outgrowth and neural lineage commitment. Results attest to (i) the strong role of activated microglia in regulating NSC fate, (ii) the utility of selective analytes released by activated microglia in promoting neurogenesis and neuritogenesis, and (iii) the need to protect transplanted NSCs from the host inflammatory microenvironment to ensure their survival and functionality in treating neurological disorders.

Nephron sparing endoscopic treatment for primary carcinoma of the renal calyx: A case report and literature review.

Primary carcinoma of the renal calyx is extremely rare. The present study reported nephron sparing endoscopic treatment for primary carcinoma of the renal calyx. An 81-year-old female presented with a 1-year history of intermittent painless gross hematuria. Computed tomography and X-ray of the urinary tract were unable to definitively identify any lesion. Flexible ureteroscopic examination revealed a tumor with epicenter in the lower calyx of the right kidney, with additional involvement around the calyx. Biopsies were obtained and pathology revealed low-grade urothelial carcinoma. Considering additional co-morbidities, the patient elected to undergo endoscopic management with thulium laser. The present report described the feasibility of flexible ureteroscopic thulium laser resection for the treatment of renal calyx carcinoma.

Validation of a culturally compliant voiding platform for urodynamics in African vesicovaginal fistula patients.

INTRODUCTION AND HYPOTHESIS: Most patients in regions where obstetric vesicovaginal fistulas (VVF) are endemic void using a squatting posture. Additionally, many patients continue to have lower urinary tract symptoms (LUTS) following fistula closure. We designed and validated a prototype platform that allows urodynamic studies to be performed in a squatting position and conducted a pilot study to assess uroflowmetry in this patient population. METHODS: Sixteen patients with persistent LUTS following fistula surgery were recruited. Posture measurements were taken in each patient's natural voiding posture on the ground and were then repeated using the platform. Nine patients with persistent urinary incontinence also underwent uroflowmetry. The data were compared with normal values in different nomograms. Paired t tests were used to determine significant differences in posture. One-way ANOVA was used to determine statistical significance between flow rate values. RESULTS: Only the heel-to-heel distance (H-H) measure of posture was significantly increased on the platform compared with on the ground. The mean corrected Qmax was 0.89 ± 0.46. Flow rate values were significantly lower than mean normal flow rates obtained from the nomograms. In general, the patients' uroflowmetry patterns were similar to those indicative of impaired detrusor function. CONCLUSION: A platform for conducting urodynamic studies in a squatting posture was successfully validated in the VVF patient population. The finding of increased H-H on the platform is expected, since the patient must accommodate a large funnel for urine collection. The pilot data suggest that patients with persistent urinary incontinence following VVF closure may also have significant voiding dysfunction.

Validation of genetically matched wild-type strain and lysyl oxidase-like 1 knockout mouse model of pelvic organ prolapse.

OBJECTIVES: Lysyl oxidase-like 1 knockout (Loxl1) mice demonstrate deficient elastin homeostasis associated with pelvic organ prolapse (POP). To further investigate the pathophysiology of POP in these animals, a genetically matched homozygous positive (Loxl1) or wild-type strain is needed. This study sought to create and validate genetically matched Loxl1 and Loxl1 strains. METHODS: Female Loxl1 mice were backcrossed with male wild-type mice. The resultant heterozygous mice were bred to produce Loxl1 and Loxl1 mice, whose genotype was confirmed by polymerase chain reaction (PCR). Multiparous female Loxl1 (n = 7) and Loxl1 (n = 9) mice were assessed for POP weekly for 12 weeks after their first vaginal delivery. Pelvic organ prolapse was compared between groups using a Kaplan-Meier survival curve with P of less than 0.05 indicating a significant difference. Vaginal connective tissue histologic finding was assessed qualitatively and quantitatively. RESULTS: There were no significant differences between the groups in age or parity. Of the 7 Loxl1 mice, 4 developed prolapse by 8 weeks and 6 by 12 weeks postpartum. No Loxl1 mouse prolapsed. Loxl1 mice had significantly larger vaginas as determined by area within the lumen and total cross-sectional tissue area. Striated muscle fibers of the urethra in Loxl1 mice were less organized, shorter, and thinner than in Loxl1 mice. CONCLUSIONS: Genetically matched Loxl1 and Loxl1 strains can be reliably created by a backcross method and differentiate in their prolapse phenotype. Loxl1 mice demonstrate pathology primarily characterized by enlargement of the vagina. Further studies are needed to elucidate the cause of this finding.

Animal models of female pelvic organ prolapse: lessons learned.

Pelvic organ prolapse is a vaginal protrusion of female pelvic organs. It has high prevalence worldwide and represents a great burden to the economy. The pathophysiology of pelvic organ prolapse is multifactorial and includes genetic predisposition, aberrant connective tissue, obesity, advancing age, vaginal delivery and other risk factors. Owing to the long course prior to patients becoming symptomatic and ethical questions surrounding human studies, animal models are necessary and useful. These models can mimic different human characteristics - histological, anatomical or hormonal, but none present all of the characteristics at the same time. Major animal models include knockout mice, rats, sheep, rabbits and nonhuman primates. In this article we discuss different animal models and their utility for investigating the natural progression of pelvic organ prolapse pathophysiology and novel treatment approaches.