Human vs machine: identifying ChatGPT-generated abstracts in Gynecology and Urogynecology.

BACKGROUND: ChatGPT, a publicly available artificial intelligence large language model, has allowed for sophisticated artificial intelligence technology on demand. Indeed, use of ChatGPT has already begun to make its way into medical research. However, the medical community has yet to understand the capabilities and ethical considerations of artificial intelligence within this context, and unknowns exist regarding ChatGPT's writing abilities, accuracy, and implications for authorship. OBJECTIVE: We hypothesize that human reviewers and artificial intelligence detection software differ in their ability to correctly identify original published abstracts and artificial intelligence-written abstracts in the subjects of Gynecology and Urogynecology. We also suspect that concrete differences in writing errors, readability, and perceived writing quality exist between original and artificial intelligence-generated text. STUDY DESIGN: Twenty-five articles published in high-impact medical journals and a collection of Gynecology and Urogynecology journals were selected. ChatGPT was prompted to write 25 corresponding artificial intelligence-generated abstracts, providing the abstract title, journal-dictated abstract requirements, and select original results. The original and artificial intelligence-generated abstracts were reviewed by blinded Gynecology and Urogynecology faculty and fellows to identify the writing as original or artificial intelligence-generated. All abstracts were analyzed by publicly available artificial intelligence detection software GPTZero, Originality, and Copyleaks, and were assessed for writing errors and quality by artificial intelligence writing assistant Grammarly. RESULTS: A total of 157 reviews of 25 original and 25 artificial intelligence-generated abstracts were conducted by 26 faculty and 4 fellows; 57% of original abstracts and 42.3% of artificial intelligence-generated abstracts were correctly identified, yielding an average accuracy of 49.7% across all abstracts. All 3 artificial intelligence detectors rated the original abstracts as less likely to be artificial intelligence-written than the ChatGPT-generated abstracts (GPTZero, 5.8% vs 73.3%; P<.001; Originality, 10.9% vs 98.1%; P<.001; Copyleaks, 18.6% vs 58.2%; P<.001). The performance of the 3 artificial intelligence detection software differed when analyzing all abstracts (P=.03), original abstracts (P<.001), and artificial intelligence-generated abstracts (P<.001). Grammarly text analysis identified more writing issues and correctness errors in original than in artificial intelligence abstracts, including lower Grammarly score reflective of poorer writing quality (82.3 vs 88.1; P=.006), more total writing issues (19.2 vs 12.8; P<.001), critical issues (5.4 vs 1.3; P<.001), confusing words (0.8 vs 0.1; P=.006), misspelled words (1.7 vs 0.6; P=.02), incorrect determiner use (1.2 vs 0.2; P=.002), and comma misuse (0.3 vs 0.0; P=.005). CONCLUSION: Human reviewers are unable to detect the subtle differences between human and ChatGPT-generated scientific writing because of artificial intelligence's ability to generate tremendously realistic text. Artificial intelligence detection software improves the identification of artificial intelligence-generated writing, but still lacks complete accuracy and requires programmatic improvements to achieve optimal detection. Given that reviewers and editors may be unable to reliably detect artificial intelligence-generated texts, clear guidelines for reporting artificial intelligence use by authors and implementing artificial intelligence detection software in the review process will need to be established as artificial intelligence chatbots gain more widespread use.

Trainee Perspectives Regarding the Effect of the Dobbs v. Jackson Women's Health Organization Supreme Court Decision on Obstetrics and Gynecology Training.

Objectives: We aimed to describe obstetrics and gynecology (OBGYN) trainees' anticipation of how the Dobbs v. Jackson Women's Health Organization (Dobbs) U.S. Supreme Court decision may affect their training. Methods: A REDCap survey of OBGYN residents and fellows in the United States from September 19, 2022, to December 1, 2022, queried trainees' anticipated achievement of relevant Accreditation Council for Graduate Medical Education (ACGME) training milestones, their concerns about the ability to provide care and concern about legal repercussions during training, and the importance of OBGYN competence in managing certain clinical situations for residency graduates. The primary outcome was an ACGME program trainee feeling uncertain or unable to obtain the highest level queried for a relevant ACGME milestone, including experiencing 20 abortion procedures in residency. Results: We received 469 eligible responses; the primary outcome was endorsed by 157 respondents (33.5%). After correction for confounders, significant predictors of the primary outcome were state environment (aOR = 3.94 for pending abortion restrictions; aOR = 2.71 for current abortion restrictions), trainee type (aOR = 0.21 for fellow vs. resident), and a present or past Ryan Training Program in residency (aOR = 0.55). Although the vast majority of trainees believed managing relevant clinical situations are key to OBGYN competence, 10%-30% of trainees believed they would have to stop providing the standard of care in clinical situations during training. Conclusions: This survey of OBGYN trainees indicates higher uncertainty about achieving ACGME milestones and procedural competency in clinical situations potentially affected by the Dobbs decision in states with legal restrictions on abortion.

Dietary Intake and Symptom Severity in Women with Fecal Incontinence.

INTRODUCTION AND HYPOTHESIS: The goal of this study was to determine whether dietary fat/fiber intake was associated with fecal incontinence (FI) severity. METHODS: Planned supplemental analysis of a randomized clinical trial evaluating the impact of 12-week treatment with percutaneous tibial nerve stimulation versus sham in reducing FI severity in women. All subjects completed a food screener questionnaire at baseline. FI severity was measured using the seven-item validated St. Mark's (Vaizey) FI severity scale. Participants also completed a 7-day bowel diary capturing the number of FI-free days, FI events, and bowel movements per week. Spearman's correlations were calculated between dietary, St. Mark's score, and bowel diary measures. RESULTS: One hundred and eighty-six women were included in this analysis. Mean calories from fats were 32% (interquartile range [IQR] 30-35%). Mean dietary fiber intake was 13.9 ± 4.3 g. The percentage of calories from fats was at the higher end of recommended values, whereas fiber intake was lower than recommended for adult women (recommended values: calories from fat 20-35% and 22-28 g of fiber/day). There was no correlation between St. Mark's score and fat intake (r = 0.11, p = 0.14) or dietary fiber intake (r = -0.01, p = 0.90). There was a weak negative correlation between the number of FI-free days and total fat intake (r = -0.20, p = 0.008). Other correlations between dietary fat/fiber intake and bowel diary measures were negligible or nonsignificant. CONCLUSION: Overall, in women with moderate to severe FI, there was no association between FI severity and dietary fat/fiber intake. Weak associations between FI frequency and fat intake may suggest a role for dietary assessment in the evaluation of women with FI.

Correlation Between Mobile-Application Electronic Bowel Diary and Validated Questionnaires in Women with Fecal Incontinence.

INTRODUCTION AND HYPOTHESIS: Despite growing interest in a mobile-app bowel diary to assess fecal incontinence (FI) symptoms, data are limited regarding the correlation between mobile-app diary and questionnaire-based outcomes. The primary aim is to determine whether percentage reduction in FI episodes (FIEs)/week recorded on a mobile-app diary correlates with changes in scores of validated FI-symptom measures from baseline to 12 weeks in women with FI undergoing percutaneous tibial nerve stimulation (PTNS) versus sham. METHODS: This is a planned secondary analysis of a multicenter randomized trial in which women with FI underwent PTNS or sham. FIEs were collected using a mobile-app diary at baseline and after 12 weekly sessions. FI-symptom-validated measures included St. Mark's, Accidental Bowel Leakage Evaluation, FI Severity Index (FISI), Colorectal Anal Distress Inventory, Colorectal Anal Impact Questionnaire, FI Quality of Life, Patient Global Impression of Improvement (PGI-I), and Patient Global Symptom Control (PGSC) rating. Spearman's correlation coefficient (ρ) was computed between %-reduction in FIEs/week and change in questionnaire scores from baseline to 12 weeks. Significance was set at 0.005 to account for multiple comparisons. RESULTS: Baseline characteristics of 163 women (109 PTNS, 54 sham) include mean age 63.4±11.6, 81% white, body mass index 29.4±6.6 kg/m2, 4% previous FI surgeries, 6.6±5.5 FIEs/week, and St. Mark's score 17.4±2.6. A significant correlation was demonstrated between %-reduction in FIEs/week and all questionnaires (p<0.005). A moderate-strength correlation (|ρ|>0.4) was observed for St. Mark's (ρ=0.48), FISI (ρ=0.46), PGI-I (ρ=0.51), and PGSC (ρ=-0.43). CONCLUSIONS: In women with FI randomized to PTNS versus sham, a moderate correlation was noted between FIEs measured via mobile-app diary and FI-symptom-validated questionnaire scores.

Remodeling of murine vaginal smooth muscle function with reproductive age and elastic fiber disruption.

Advanced maternal age during pregnancy is associated with increased risk of vaginal tearing during delivery and maladaptive postpartum healing. Although the underlying mechanisms of age-related vaginal injuries are not fully elucidated, changes in vaginal microstructure may contribute. Smooth muscle cells promote the contractile nature of the vagina and contribute to pelvic floor stability. While menopause is associated with decreased vaginal smooth muscle content, whether contractile changes occur before the onset of menopause remains unknown. Therefore, the first objective of this study was to quantify the active mechanical behavior of the murine vagina with age. Further, aging is associated with decreased vaginal elastin content. As such, the second objective was to determine if elastic fiber disruption alters vaginal contractility. Vaginal samples from mice aged 2-14 months were used in maximum contractility experiments and biaxial extension-inflation protocols. To evaluate the role of elastic fibers with age, half of the vaginal samples were randomly allocated to enzymatic elastic fiber disruption. Contractile potential decreased and vaginal material stiffness increased with age. These age-related changes in smooth muscle function may be due, in part, to changes in microstructural composition or contractile gene expression. Furthermore, elastic fiber disruption had a diminished effect on smooth muscle contractility in older mice. This suggests a decreased functional role of elastic fibers with age. Quantifying the age-dependent mechanical contribution of smooth muscle cells and elastic fibers to vaginal properties provides a first step towards better understanding how age-related changes in vaginal structure may contribute to tissue integrity and healing. STATEMENT OF SIGNIFICANCE: Advanced maternal age at the time of pregnancy is linked to increased risks of vaginal tearing during delivery, postpartum hemorrhaging, and the development of pelvic floor disorders. While the underlying causes of increased vaginal injuries with age and associated pathologies remain unclear, changes in vaginal microstructure, such as elastic fibers and smooth muscle cells, may contribute. Menopause is associated with fragmented elastic fibers and decreased smooth muscle content; however, how reproductive aging affects changes in the vaginal composition and the mechanical properties remains unknown. Quantifying the mechanical contribution of smooth muscle cells and elastic fibers to vaginal properties with age will advance understanding of the potential structural causes of age-related changes to tissue integrity and healing.

Linguistic Differences by Gender in Letters of Recommendation for Maternal-Fetal Medicine Fellowship Applicants.

OBJECTIVE: As in many realms of academia and medicine, in obstetrics and gynecology, women experience gender bias in residency evaluations and academic promotions. More specifically, women in Maternal-Fetal Medicine (MFM) are underrepresented within departmental leadership positions. As a means of identifying spaces where bias may exist, multiple investigators have previously reported on gender bias in letters of recommendation (LORs) for residency and subspecialty training programs. We aimed to determine if linguistic differences exist in LORs for self-identified male and female applicants to MFM fellowship at an academic institution. STUDY DESIGN: This was a retrospective single-site cohort study from 2019 to 2021. Data collected included applicant's age, self-reported race/ethnicity and gender, geographic region of residency, step 1 and 2 scores, scholarly and volunteer activities, and number of LORs. The Linguistic Inquiry and Word Count (LIWC) software, a validated text analysis program, was used to characterize LOR linguistic content. Multivariable analysis was used to compare letter characteristics to applicant demographics. RESULTS: A total of 212 applications were reviewed, including 808 LORs. Women comprised 76.9% of applicants, and men 23.1%. Most applicants identified as non-Hispanic White (52.8%). Men were more likely to be international medical graduates (20 vs. 6%, p ≤ 0.01), and women reported more volunteer activities (7.1 ± 5.1 vs. 5.5 ± 4.3, p = 0.04). There were no differences in step scores, number of research projects, or number of LORs. Multivariable analysis controlling for applicant race, step 1 score, and gender of letter writer revealed that letters written for males contained significantly more references to the word category cognitive processes (7.4 ± 0.2 vs. 7.1 ± 0.1, p = 0.046), specifically in reference to the subcategories of certainty and differentiation. CONCLUSION: We identified linguistic differences in LORs written for MFM applicants, suggesting potential bias in the style of writing for male and female physicians applying to this field. KEY POINTS: · Gender bias exists in the evaluation and promotion of women in medicine.. · We sought to determine whether it also exists in letters of recommendation for MFM fellowship.. · Previous studies have examined gender bias in letters of recommendation for other specialties.. · Linguistic bias was detected in letters of recommendation for MFM fellowship from 2019 through 2021.. · We found evidence of linguistic differences based on gender of applicant and letter writers..

Quantification of senescence-associated secretory phenotype proteins in the vaginal secretions of pre- and postmenopausal women with and without prolapse.

Objectives: Cellular senescence has been proposed as a pathophysiologic driver in the development of pelvic organ prolapse (POP), especially during aging. In this study, we aimed to determine if markers of cell senescence can be quantified from vaginal secretions collected from pre- and postmenopausal women with and without POP. Methods: Vaginal swabs were collected from 81 women in four groups: premenopausal with (pre-P) and without prolapse (pre-NP), and postmenopausal with (post-P) and without prolapse (post-NP). Multiplex immunoassays (MagPix) were then used to detect and quantify the presence of 10 SASP proteins in vaginal secretions. Results: The total protein concentration of vaginal secretions differed significantly among the four groups (P = 0.003) with highest mean concentrations in pre-P [16, interquartile range (IQR) = 4.6, 38.3 µg/µL] and lowest mean concentrations in post-P (4.4, IQR = 2.6, 7 µg/µL). The normalized concentrations of several SASP markers differed significantly among groups, with the highest concentrations being seen in the post-P group, and the lowest concentrations being in the pre-NP group. Using these key markers, we then constructed receiver-operator curves to determine the relative sensitivity and specificity of these markers in predicting prolapse. Conclusions: In this study, we found that SASP proteins can be detected and quantified in vaginal secretions. Several of these markers were differentially expressed among the four groups studied, with the highest normalized concentrations of SASP markers found among postmenopausal women with prolapse. Overall, the data support the theory that senescence is associated with prolapse during aging but that other factors may be important in younger women who develop POP before menopause.

Smooth muscle contribution to vaginal viscoelastic response.

Smooth muscle cells contribute to the mechanical function of various soft tissues, however, their contribution to the viscoelastic response when subjected to multiaxial loading remains unknown. The vagina is a fibromuscular viscoelastic organ that is exposed to prolonged and increased pressures with daily activities and physiologic processes such as vaginal birth. The vagina changes in geometry over time under prolonged pressure, known as creep. Vaginal smooth muscle cells may contribute to creep. This may be critical for the function of vaginal and other soft tissues that experience fluctuations in their biomechanical environment. Therefore, the objective of this study was to develop methods to evaluate the contribution of smooth muscle to vaginal creep under multiaxial loading using extension - inflation tests. The vaginas from wildtype mice (C57BL/6 × 129SvEv; 3-6 months; n = 10) were stimulated with various concentrations of potassium chloride then subjected to the measured in vivo pressure (7 mmHg) for 100 s. In a different cohort of mice (n = 5), the vagina was stimulated with a single concentration of potassium chloride then subjected to 5 and 15 mmHg. A laser micrometer measured vaginal outer diameter in real-time. Immunofluorescence evaluated the expression of alpha-smooth muscle actin and myosin heavy chain in the vaginal muscularis (n = 6). When smooth muscle contraction was activated, vaginal creep behavior increased compared to the relaxed state. However, increased pressure decreased the active creep response. This study demonstrated that extension - inflation protocols can be used to evaluate smooth muscle contribution to the viscoelastic response of tubular soft tissues.

Association Between Enlarged Genital Hiatus and Composite Surgical Failure After Vaginal Hysterectomy With Uterosacral Ligament Suspension.

IMPORTANCE: The impact of a persistently enlarged genital hiatus (GH) after vaginal hysterectomy with uterosacral ligament suspension on prolapse outcomes is currently unclear. OBJECTIVES: This secondary analysis of the Study of Uterine Prolapse Procedures Randomized trial was conducted among participants who underwent vaginal hysterectomy with uterosacral ligament suspension. We hypothesized that women with a persistently enlarged GH size would have a higher proportion of prolapse recurrence. STUDY DESIGN: Women who underwent vaginal hysterectomy with uterosacral ligament suspension as part of the Study of Uterine Prolapse Procedures Randomized trial (NCT01802281) were divided into 3 groups based on change in their preoperative to 4- to 6-week postoperative GH measurements: (1) persistently enlarged GH, 2) improved GH, or (3) stably normal GH. Baseline characteristics and 2-year surgical outcomes were compared across groups. A logistic regression model for composite surgical failure controlling for advanced anterior wall prolapse and GH group was fitted. RESULTS: This secondary analysis included 81 women. The proportion with composite surgical failure was significantly higher among those with a persistently enlarged GH (50%) compared with a stably normal GH (12%) with an unadjusted risk difference of 38% (95% confidence interval, 4%-68%). When adjusted for advanced prolapse in the anterior compartment at baseline, the odds of composite surgical failure was 6 times higher in the persistently enlarged GH group compared with the stably normal group (95% confidence interval, 1.0-37.5; P = 0.06). CONCLUSION: A persistently enlarged GH after vaginal hysterectomy with uterosacral ligament suspension for pelvic organ prolapse may be a risk factor for recurrent prolapse.

Preoperative Simulation of Retropubic Midurethral Sling to Decrease Bladder Perforation Rate Among Obstetrics and Gynecology Residents.

IMPORTANCE: Bladder perforation is an often avoidable complication of retropubic midurethral sling procedures. Bladder injury rates decrease with surgeon experience, but literature on techniques to train novice surgeons is limited. OBJECTIVE: Our objective was to decrease the bladder perforation rate among obstetrics and gynecology residents during retropubic midurethral sling procedures through implementation of an instructional video and low-fidelity simulation. STUDY DESIGN: A baseline bladder perforation rate was determined by retrospective chart review. A prospective educational intervention, consisting of a 10-minute instructional video with preoperative simulation using a simple bony pelvis model, was then implemented among residents on the urogynecology service from December 2017 through March 2020. The primary outcome was the change in the bladder perforation rate. Compliance with the intervention protocol was a secondary outcome. Categorical data were evaluated using the χ 2 or Fisher exact test. Continuous variables were assessed using the Student t test or Mann-Whitney U test as appropriate. RESULTS: Two hundred fifteen retropubic midurethral sling cases were included in analysis. There were no significant demographic differences between the patients undergoing surgery preintervention and postintervention. Resident surgeons were in their second (47.4%) and third (52.6%) years of training. The postintervention bladder perforation rate was 6.5%, which is a 35% reduction from the preintervention perforation rate of 10% ( P = 0.19). The instructional video and preoperative simulation were successfully implemented in 193 of 215 (89.8%) eligible cases. CONCLUSION: Despite high compliance, the combination of the instructional video and preoperative low-fidelity bony pelvis simulation was not effective in reducing tension-free vaginal tape-associated bladder perforations among residents.

Linguistic Differences by Gender in Letters of Recommendation for Female Pelvic Medicine and Reconstructive Surgery Fellowship Applicants From 2010 to 2020.

IMPORTANCE: Linguistic differences suggestive of gender bias have been detected in letters of recommendation (LOR) for female and male residency and fellowship program applicants within multiple medical specialties. OBJECTIVE: The aim of the study was to determine whether linguistic differences exist in LOR for female and male physicians applying to female pelvic medicine and reconstructive surgery (FPMRS) fellowship. STUDY DESIGN: A retrospective analysis of FPMRS fellowship applications submitted to a university-affiliated academic center from 2010 to 2020 was performed. Linguistic Inquiry and Word Count, a text analysis software, was used to characterize the linguistic content of letters. Multivariable analysis was used to compare letter characteristics with applicant and letter writer demographics. RESULTS: Of 306 applications reviewed, 221 (72.2%) applicants were female and 85 (27.8%) were male. Of the 1,062 letters analyzed, 457 (43.0%) were written by female letter writers, 586 (55.2%) by males, and 19 (1.8%) were a combination. Multivariable analysis controlling for race, Step 1 score, and letter writer gender demonstrated more frequent use of affiliation words for female applicants compared with males (3.1% ± 0.3 vs. 2.9% ± 0.3, P = 0.02). No additional differences were noted in average letter length or all other linguistic categories analyzed. Multiple differences were detected between writing styles of female and male letter writers, including average letter length, use of multiple word categories, and use of communal (relationship-oriented) language. Data were stratified into 2-year periods and no longitudinal trends in linguistic differences were detected. CONCLUSIONS: No linguistic differences, suggestive of gender bias, were found between female and male applicants to FPMRS fellowship.

Linguistic Differences by Gender in Letters of Recommendation for Minimally Invasive Gynecologic Surgery Fellowship Applicants.

OBJECTIVE: Various surgical specialties have reported gender bias in letters of recommendation (LOR). We aimed to determine if linguistic differences exist in LOR for female and male physicians applying to Fellowship in Minimally Invasive Gynecologic Surgery (FMIGS). DESIGN: Retrospective cohort study including application cycles 2019 and 2020. SETTING: Academic university hospital. PARTICIPANTS: FMIGS applicants. RESULTS: Applicant demographic and baseline data included age, race, gender, geographical region of residency training, Step 1 and 2 scores, number of research and volunteer activities, Alpha Omega Alpha and Gold Humanism status and number of LOR, as well as the gender and academic rank of the letter writer. The Linguistic Inquiry and Word Count software, a validated text analysis program, was used to characterize LOR linguistic content. A total of 118 applications, including 391 letters, were analyzed. Seventy-six (64.4%) applicants were female and 42 (35.6%) were male. Most female applicants were white (46% vs. 36%, p = 0.04), had Alpha Omega Alpha status (13% vs. 0%, p = 0.01), higher Step 2 scores (239.7 vs. 230.4, p < 0.01), and more service activities (7.7 vs. 4.7, p < 0.01), compared to male applicants. Male applicants were more likely to graduate from international medical schools (45% vs. 16%, p < 0.01). Female authors wrote 159 LOR, and male authors wrote 232. Following multivariable analysis controlling for race, Step 1 score and letter writer gender, no significant differences in average LOR word count for female and male applicants (406.7 ± 24.2 words vs. 340.1 ± 35.4 words), or differences in Linguistic Inquiry and Word Count linguistic categories existed. CONCLUSIONS: Although Baseline differences were noted between female and male FMIGS applicants, no differences in LOR length or linguistic categories were noted. These results likely reflect the impact of female predominance and increased efforts to address gender bias within Obstetrics and Gynecology.

Effect of gelatin methacryloyl hydrogel on healing of the guinea pig vaginal wall with or without mesh augmentation.

INTRODUCTION AND HYPOTHESIS: The aims of this study were to evaluate the effectiveness of gelatin methacryloyl as an adjunct to anterior vaginal wall injury with or without vaginal mesh compared with traditional repair with suture. METHODS: Virginal cycling Hartley strain guinea pigs (n = 60) were randomized to undergo surgical injury and repair using either polyglactin 910 suture or gelatin methacryloyl for epithelium re-approximation or anterior colporrhaphy with mesh augmentation using either polyglactin 910 suture or gelatin methacryloyl for mesh fixation and epithelium re-approximation. Noninjured controls (n = 5) were also evaluated. After 4 days, 4 weeks, or 3 months, tissues were analyzed by hematoxylin & eosin in addition to immunolabeling for macrophages, leukocytes, smooth muscle, and fibroblasts. RESULTS: Surgical injury repaired with suture was associated with increased inflammation and vessel density compared with gelatin methacryloyl. Vimentin and α-smooth muscle actin expression were increased with gelatin methacryloyl at 4 days (p = 0.0026, p = 0.0272). There were no differences in changes in smooth muscle or overall histomorphology after 3 months between the two closure techniques. Mesh repair with suture was also associated with increased inflammation and vessel density relative to gelatin methacryloyl. Quantification of collagen content by picrosirius red staining revealed increased thick collagen fibers throughout the implanted mesh with gelatin methacryloyl compared with suture at 4 weeks (0.62 ± 0.01 µm2 vs 0.55 ± 0.01, p = 0.018). Even at the long-term time point of 3 months, mesh repair with suture resulted in a profibrotic encapsulation of the mesh fibers, which was minimal with gelatin methacryloyl. Smooth muscle density was suppressed after mesh implantation returning to baseline levels at 3 months regardless of fixation with suture or gelatin methacryloyl. CONCLUSIONS: These results suggest that gelatin methacryloyl might be a safe alternative to suture for epithelium re-approximation and anchoring of prolapse meshes to the vagina and may improve chronic inflammation in the vaginal wall associated with mesh complications.

Induction of Cellular Senescence in Rat Vaginal Fibroblasts and Treatment With Senolytics: An in Vitro Model for the Study of Pelvic Organ Prolapse.

OBJECTIVE: The objective of this study was to develop an in vitro model of cellular senescence using rat vaginal fibroblasts and determine the effects of treatment with senolytics. METHODS: Rat vaginal tissue biopsies were collected. Primary vaginal fibroblasts were isolated and characterized by immunofluorescence. To induce cellular senescence, fibroblasts were treated with etoposide at 3, 10, and 20 mM for 24 hours, followed by treatment with the senolytics dasatinib (1 mM) and/or quercetin (20 mM). After treatment, RNA was extracted and the expression of selected genes was quantified. Immunostaining of senescence markers was also performed. RESULTS: Fibroblasts were confirmed by positive immunostaining for α-smooth muscle actin and vimentin, and negative immunostaining for pan-cytokeratin. Treatment with etoposide resulted in a dose-dependent increase in expression of the senescence-associated secretory phenotype markers MMP-7, MMP-9, and IL-b1 (P < 0.05) compared with controls. Immunostaining showed increased expression of γ-H2A and p21 after treatment with etoposide. Cells treated with dasatinib and quercetin after etoposide treatment had decreased expression of p21, MMP-7, MMP-9, and IL-1b compared with cells treated only with etoposide (P < 0.05). CONCLUSIONS: Upregulation of senescence-associated factors provided evidence that senescence can be induced in vaginal fibroblasts in vitro. Furthermore, treatment with the senolytics dasatinib and quercetin abrogated the senescence phenotype induced by etoposide in rat vaginal fibroblasts. Our findings provide a novel model for the study and development of new therapies targeting the disordered extracellular matrix associated with pelvic organ prolapse.

Impact of vaginal distention on cell senescence in an animal model of pelvic organ prolapse.

OBJECTIVE: Cellular senescence, associated with aging, leads to impaired tissue regeneration. We hypothesize that vaginal injury initiates cell senescence, further propagated during aging resulting in pelvic organ prolapse (POP). Our objective was to employ a mouse model of POP (Fibulin-5 knockout mice, Fbln5-/-) to determine if vaginal distention leads to cellular senescence and POP. METHODS: 6wk old females [wild-type (WT), n = 81; Fbln5-/-, n = 47)] were assigned to control vs vaginal distention, which approximated vaginal delivery. Serial POP measurements were obtained until vagina were harvested from euthanized mice at 24, 48, 72 h and 1wk. Markers of cell senescence were quantified by immunofluorescence. DNA damage was assessed with γ-H2Ax. RESULTS: WT distended mice showed decreased p53 (p = 0.0230) and γ-H2Ax (p = 0.0008) in vaginal stromal cells at 1wk compared to controls. In WT mice, SA-ß-Gal activity increased 1wk after distention (p = 0.05). In Fbln5-/- mice, p53 and γ-H2Ax did not decrease, but p16 decreased 72 h after distention (p = 0.0150). SA-ß-Gal activity also increased in Fbln5-/-, but at earlier time points and 1wk after distention (p < 0.0001). Fbln5-/- mice developed POP after distention earlier than non distended animals (p = 0.0135). CONCLUSIONS: Vaginal distention downregulates p53 and γ-H2Ax in WT mice, thereby promoting cell proliferation 1wk after injury. This was absent among Fbln5-/- distention mice suggesting they do not escape senescence. These findings indicate a failure of cellular protection from senescence in animals predisposed to POP.

Perioperative outcomes following pelvic floor reconstruction in women with hereditary disorders of connective tissue: a retrospective cohort study.

INTRODUCTION AND HYPOTHESIS: Women with hereditary disorders of connective tissue (HDCT) are at increased risk of pelvic organ prolapse (POP) and stress urinary incontinence (SUI). We hypothesized that patients would have increased incidence and severity of perioperative complications up to 6 weeks after surgeries for POP/SUI. Secondary objectives were to compare pre- and post-operative pelvic floor symptoms and anatomical support as well as pelvic floor disorder recurrence. METHODS: In this multi-center retrospective cohort study, we identified patients with HDCTs by patient history and ICD-9 codes over an 11-year period. Controls without HDCTs were matched 2:1 to the primary POP or SUI procedure and surgeon. Demographic characteristics, perioperative pelvic floor information and complications were collected. A sample size of 65 HDCT patients and 130 controls was calculated to detect a 20% difference in complications with 80% power and alpha of 0.05. RESULTS: We identified 59 HDCT patients and 118 controls. Of the women with HDCTs, 49% had Ehlers-Danlos, 22% joint hypermobility syndrome, 15% Marfan syndrome, and 14% had others. Compared with controls, HDCT patients had more total perioperative complications (46% vs 22%, p = 0.002); an age-adjusted relative risk of complications was 1.4 (CI 0.7-2.6). HDCT patients had more Clavien-Dindo grades I and II complications (p = 0.02, 0.03) and more hospital readmissions (14% vs 3%, p = 0.01) than controls. There was no difference in the incidence of specific complications nor was there a difference in recurrence of POP (10%) or SUI (11%) between groups. CONCLUSIONS: Patients with HDCTs had more Clavien-Dindo grade I and II complications following pelvic floor reconstructive surgery and more readmissions.

Does Living With Human Immunodeficiency Virus Increase Pelvic Reconstructive Surgery Perioperative Complication Risk? A Multicenter Retrospective Cohort Study.

OBJECTIVE: To determine if women with human immunodeficiency virus (HIV) undergoing pelvic reconstructive surgery (PRS) have an increased risk of perioperative and postoperative complications compared with HIV-negative controls. STUDY DESIGN: Multicenter, retrospective matched cohort study of patients with and without HIV infection who underwent PRS between 2006 and 2016. Cases were identified using International Classification of Disease, 9th edition Clinical Modification and 10th edition Clinical Modification and current procedural terminology (CPT) codes encompassing HIV diagnoses and pelvic reconstructive surgeries. Controls were identified as patients without HIV who underwent similar procedures, performed by the same surgeon during the same 1-year period as surgeries performed on patients with HIV. Cases were matched to controls at a ratio of 1:3. The primary outcome was composite complication rate within 1 year of surgery. RESULTS: Sixty-three patients with HIV and 187 controls were identified. There was no difference in the composite complication rate between women with HIV and HIV-negative women (36.5% vs 30.0%, P = 0.15) over 1 year. However, 19.1% of patients with HIV compared with 5.4% controls had Clavien Dindo Grade I complications (P = 0.002), and 11.1% of HIV patients had urinary retention within 6 weeks of surgery compared with 3.2% of controls (P = 0.02). After multivariable logistic regression used to adjust for confounders, living with HIV was not associated with an increased risk of complications. CONCLUSIONS: Patients living with HIV are not at an increased risk of complications within 1 year of PRS compared with patients without HIV.

Protease Inhibition Improves Healing of The Vaginal Wall after Obstetrical Injury: Results from a Preclinical Animal Model.

Vaginal delivery with obstetrical trauma is a risk factor for pelvic organ prolapse later in life. Loss of fibulin-5 (FBLN5), an elastogenesis-promoting cellular matrix protein, results in prolapse in mice. Here, we evaluated effects of pregnancy, parturition, and obstetrical injury on FBLN5 content, elastic fibers, biomechanics, and histomorphology of the vaginal wall in rats. Further, we analyzed the effects of actinonin, a protease inhibitor, on obstetrical injury of the vaginal wall. Vaginal FBLN5 decreased significantly in pregnancy, and injury resulted in further downregulation. Stiffness of the vaginal wall decreased 82% in pregnant rats and 74% (p = 0.019) with injury relative to uninjured vaginal delivery controls at 3d. Actinonin ameliorated loss of FBLN5, rescued injury-induced loss of elastic fibers and biomechanical properties after parturition, and reduced the area of injury 10-fold. We conclude that pregnancy and parturition have a profound impact on vaginal FBLN5 and biomechanics of the vaginal wall. Further, obstetrical injury has significant deleterious impact on recovery of the vaginal wall from pregnancy. Actinonin, a non-specific matrix metalloprotease inhibitor, improved recovery of the parturient vaginal wall after obstetrical injury.

Comparisons of Functional Apical Support After Sacral Hysteropexy Versus Sacral Colpopexy: A Cadaveric Study.

OBJECTIVES: Prolapse procedures with uterine preservation offer an alternative to colpopexy with hysterectomy. Few studies have examined the differences in anatomic or subjective outcomes following sacral hysteropexy versus sacral colpopexy with hysterectomy. This study sought to compare the ability of sacral hysteropexy and sacral colpopexy with hysterectomy to resist downward traction as an estimate of apical support in human cadavers. METHODS: Sacral hysteropexy was performed on unembalmed female cadavers. A metal bolt/washer was threaded through the uterine fundus, down the cervical canal. and out the vagina and fastened to a waxed surgical filament, which ran over a fixed pulley at the table's end. Successive weights were added to provide increasing loads on the uterine fundus, and the distances traversed by the fundus were recorded. The same process was repeated after completion of a total hysterectomy (with vaginal cuff closure) and subsequent sacral colpopexy in the same specimen. Data were analyzed using paired-sample t test and repeated-measures analysis of variance (Sigma Plot version 13.0), with P ≤ 0.05 considered statistically significant. RESULTS: Eight female cadavers were utilized. With the addition of each weight, the average distance traversed by the uterine fundus or vaginal cuff gradually increased. There were no statistical differences in the distances moved by the apex between sacral hysteropexy and total hysterectomy/sacral colpopexy. CONCLUSIONS: These results suggest that functional support provided by sacral hysteropexy and sacral colpopexy with hysterectomy may be similar. Further studies are needed to correlate these findings with patient satisfaction, which may vary despite similar anatomic results.