Proregenerative extracellular matrix hydrogel mitigates pathological alterations of pelvic skeletal muscles after birth injury.

Pelvic floor disorders, including pelvic organ prolapse and urinary and fecal incontinence, affect millions of women globally and represent a major public health concern. Pelvic floor muscle (PFM) dysfunction has been identified as one of the leading risk factors for the development of these morbid conditions. Childbirth, specifically vaginal delivery, has been recognized as the most important potentially modifiable risk factor for PFM injury; however, the precise mechanisms of PFM dysfunction after parturition remain elusive. In this study, we demonstrated that PFMs exhibit atrophy and fibrosis in parous women with symptomatic pelvic organ prolapse. These pathological alterations were recapitulated in a preclinical rat model of simulated birth injury (SBI). The transcriptional signature of PFMs after injury demonstrated an impairment in muscle anabolism, persistent expression of genes that promote extracellular matrix (ECM) deposition, and a sustained inflammatory response. We also evaluated the administration of acellular injectable skeletal muscle ECM hydrogel for the prevention of these pathological alterations. Treatment of PFMs with the ECM hydrogel either at the time of birth injury or 4 weeks after injury mitigated PFM atrophy and fibrosis. By evaluating gene expression, we demonstrated that these changes are mainly driven by the hydrogel-induced enhancement of endogenous myogenesis, ECM remodeling, and modulation of the immune response. This work furthers our understanding of PFM birth injury and demonstrates proof of concept for future investigations of proregenerative biomaterial approaches for the treatment of injured pelvic soft tissues.

Impact of sex and aging on radiographic and functional parameters of the anal sphincter complex in patients with accidental bowel leakage.

AIMS: Treatment outcomes for accidental bowel leakage (ABL) may be influenced by age-related sarcopenia. We sought to determine if thickness of the anal sphincter complex on endoanal ultrasound correlated with function in women and men with ABL and if women demonstrated age-related anal sphincter thinning. METHODS: Consecutive patients with ABL presenting to our pelvic floor clinic from 2012 to 2017 were included. Clinical data were obtained from medical records. External anal sphincter (EAS), imaged by endoanal ultrasound at proximal, mid and distal locations, and IAS thickness were measured at 12, 3, 6, and 9 o'clock; puborectalis muscle (PRM) was measured at 4, 6, and 8 o'clock; and averaged. Anorectal manometry was conducted when clinically indicated. Data were compared using Mann-Whitney tests and linear regression. Results are reported as mean ± SD or median (IQR). RESULTS: Women (n = 136) were younger than men (n = 26) (61 ± 13 vs. 67 ± 13 years, p = 0.02). More women than men had pelvic surgery and less had colorectal surgery, spinal disorders, or a history of smoking (p < 0.05). Eighty-two percentage of women had an anal sphincter defect versus 31% of men (p < 0.01). All anal sphincter complex components were thinner in women than men with lower squeeze and resting pressures (p < 0.03), even in nulliparous women. Mean resting pressure was lower in older 6.1 (4.6-7.8) versus younger women 8.3 (5.0-12.9) mmHg, p = 0.04. CONCLUSIONS: Women, even nulliparous, with ABL demonstrate thinner and weaker anal sphincters than men, Aging correlated with an increase in anal sphincter thickness, suggesting that age-related changes in the intrinsic components of the anal sphincter complex associated with ABL are complex and are not always well demonstrated on endoanal ultrasound.

Recurrence of Rectal Prolapse After Surgical Repair in Women With Pelvic Organ Prolapse.

BACKGROUND: Pelvic organ prolapse is prevalent among women with rectal prolapse. OBJECTIVE: This study aimed to determine whether clinically significant pelvic organ prolapse impacts rectal prolapse recurrence after surgical repair. DESIGN: A retrospective cohort. SETTING: This study was performed at a single managed-care institution. PATIENTS: Consecutive women undergoing rectal prolapse repair between 2008 and 2016 were included. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: Full-thickness rectal prolapse recurrence was compared between 4 groups: abdominal repair without pelvic organ prolapse (AR-POP); abdominal repair with pelvic organ prolapse (AR+POP); perineal repair without pelvic organ prolapse PR-POP; and perineal repair with pelvic organ prolapse (PR+POP). Recurrence-free period and hazard of recurrence were compared using Kaplan-Meier and Cox proportional hazards methods. To identify potential confounding risk factors for rectal prolapse recurrence, the characteristics of subjects with/without recurrence were compared with univariable and multivariable analyses. RESULTS: Overall, pelvic organ prolapse was present in 33% of 112 women and was more prevalent among subjects with rectal prolapse recurrence (52.4% vs 28.6%, p = 0.04). Median follow-up was 42.5 months; rectal prolapse recurrence occurred in 18.8% at a median of 9 months. The rate of recurrence and the recurrence-free period differed significantly between groups: AR-POP 3.8%, 95.7 months; AR+POP 13.0%, 86.9 months; PR-POP 34.8%, 42.1 months; PR+POP 57.1%, 23.7 months (p < 0.001). Compared with AR-POP the HR (95% CI) of rectal prolapse recurrence was 3.1 (0.5-18.5) for AR+POP; 14.7 (3.0-72.9) for PR-POP and 31.1 (6.2-154.5) for PR+POP. Compared with AR+POP, PR+POP had a shorter recurrence-free period (p < 0.001) and a higher hazard of recurrence (HR, 10.2; 95% CI, 2.1-49.3). LIMITATIONS: The retrospective design was a limitation of this study. CONCLUSIONS: Pelvic organ prolapse was associated with a higher rectal prolapse recurrence rate and earlier recurrence in women undergoing perineal, but not abdominal, repairs. Multidisciplinary evaluation can facilitate individualized management of women with rectal prolapse. Abdominal repair should be considered in women with concomitant rectal and pelvic organ prolapse. See Video Abstract at http://links.lww.com/DCR/A513.