Intraoperative Fluorescent Ureter Visualization for Transvaginal High Uterosacral Ligament Suspension for Severe Pelvic Organ Prolapse.

INTRODUCTION AND HYPOTHESIS: We aimed to demonstrate the feasibility of ureteral navigation using intra-ureteric indocyanine green (ICG) and near-infrared fluorescence (NIRF) imaging during transvaginal high uterosacral ligament suspension for prolapse repair to reduce the risk of iatrogenic ureteral injury. METHODS: A cystoscope was inserted into the bladder, the tip of a 6-F open-end ureteral catheter was inserted into the ureteral orifices, and ICG was instilled into the ureters. The ureteral path was then clearly identified using NIRF imaging. Sutures were safely placed in the uterosacral ligaments at the level of the ischial spine, taking advantage of direct ureteral visualization. RESULTS: At the end of the procedure, diagnostic cystoscopy was performed to confirm ureteral patency. No intraoperative or postoperative complications were observed. CONCLUSIONS: Intra-ureteric ICG-NIRF imaging represents a simple, inexpensive, and reproducible trick for intraoperative ureteral detection, and could reassure surgeons during difficult operations, for instance, in the case of severe prolapse and/or when ureteral course abnormalities are expected.

The association between vulvodynia and interstitial cystitis/bladder pain syndrome: A systematic review.

BACKGROUND: Vulvodynia (VVD) is a debilitating chronic vulvar pain significantly affecting patients' quality of life. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and complex illness characterized by an unpleasant sensation related to the filling of the bladder and it strongly impacts patients' lives. The exact mechanisms of the two syndromes remain unknown, but there is an overlap between suspected pathophysiologies. OBJECTIVE: To present an overview of the current research on the association between VVD and IC/BPS. SEARCH STRATEGY: A systematic search of three electronic databases was conducted. Studies examining the correlation between VVD and IC/BPS with male and female patients aged over 18 years were included. SELECTION CRITERIA: Studies assessing the coexistence of VVD and IC/BPS were included. Reviews, letters to the editor, conference abstracts, book chapters, guidelines, Cochrane reviews, and expert opinions were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers screened the studies for eligibility. Eligible studies were screened for quality. MAIN RESULTS: A total of 13 studies were included in the final review. Among them, 11 presented a positive association between the two syndromes. The studies highlighted that VVD and IC/BPS share common comorbidities and possibly etiopathogenic pathways. CONCLUSION: VVD and IC/BPS are both complex and multifactorial syndromes. This review highlights an association between them, but additional studies on the topic should be conducted for a more precise conclusion.

Spondylodiscitis after sacral colpopexy: diagnose early to treat earlier.

Spondylodiscitis following sacral colpopexy for Pelvic Organ Prolapse (POP) represents a rare complication with severe consequences. Authors performed a literature search, from 2000 to 2022, to set a narrative review of literature. Spondylodiscitis is an uncommon but dangerous side effect of a routine surgical treatment that needs to be identified and treated right away to prevent worsening clinical consequences. Suboptimal dissection of the sacral promontory and/or site infection are associated with spondylodiscitis. When spondylodiscitis is suspected, advanced imaging methods should be used, and surgical excision shouldn't be put off after a failed course of treatment. Authors presented a case-video of a 68-year-old woman who reported severe lower back pain 7 weeks after surgery, in which sacral spondylodiscitis was diagnosed and laparoscopically treated. In this case, a laparoscopic tack and mesh removal from promontory was carried out following the patient's continued lower back pain and the antibiotic therapy's incomplete radiological remission of spondylodiscitis. The patient's radiological findings and symptoms completely resolved two weeks following the procedure.

How Old Is Too Old? Outcomes of Prolapse Native-Tissue Repair through Uterosacral Suspension in Octogenarians.

INTRODUCTION: Medical advancements are expected to lead to a substantial increase in the population of women aged 80 and older by 2050. Consequently, a significant number of individuals undergoing corrective prolapse surgery will fall into the elderly-patient category. The research indicates a notable rise in complications associated with prolapse surgery in patients older than 80, irrespective of frailty and other risk factors. Despite these challenges, the vaginal approach has been identified as the safest surgical method for pelvic organ prolapse (POP) repair in the elderly population. For this reason, we aimed to investigate the efficacy, complication rate, and functional outcomes associated with vaginal hysterectomy and an apical suspension/high uterosacral ligaments suspension as a primary technique for prolapse repair, both within a cohort of elderly patients. METHODS: We retrospectively analyzed patients who underwent transvaginal hysterectomy plus an apical suspension procedure for stage ≥ II and symptomatic genital prolapse between January 2006 and December 2013. Anatomical and functional outcomes were evaluated. The Patient Global Impression of Improvement (PGI-I) score was used to evaluate subjective satisfaction after surgery. RESULTS: Sixty-five patients were included in the analysis. The median age was 81.3 years. All individuals exhibited an anterior compartment prolapse stage II or higher, and the majority also a central prolapse stage II or higher. Notably, all participants reported symptoms of vaginal bulging. Over half of the population (58.6%) complained of incomplete bladder emptying. The intervention for all participants involved a vaginal hysterectomy with an apical suspension. Sixty-three patients (96.9%) and forty-four patients (67.6%) underwent a simultaneous anterior or posterior repair, respectively. Long-term complications (>30 days from surgery) were observed during follow-up, with a median duration of 23 ± 20 months. Seven (10.7%) anatomical recurrences were recorded, five (7.69%) concerning the anterior compartment, one (1.5%) the central, and three (4.6%) the posterior. Nevertheless, none of them necessitated further surgical intervention due to symptoms. Significant anatomical improvements for the anterior, central, and posterior compartments were noticed, compared to preoperative assessment (p < 0.001 for Aa and Ba, p < 0.001 for Ap and Bp, and p < 0.001 for C). PGI-I values established that 100% of patients were satisfied (PGI-I ≥ 2), with a median score of 1.12. Consequently, objective and subjective cure rates were 89.5% and 100%, respectively. CONCLUSION: Vaginal hysterectomy combined with apical suspension, particularly high uterosacral ligaments suspension, is a safe and effective primary surgical approach, even in elderly patients.

Enhanced recovery after surgery (ERAS) in prolapse repair: A prospective study on pre-emptive uterosacral/cervical block.

OBJECTIVE: Enhanced recovery after surgery (ERAS) protocols have been introduced in gynecology. Postoperative pain management after vaginal procedures remains a relevant issue. In the present study we aimed to evaluate the effectiveness of pre-emptive uterosacral/cervical block (PUCB) for postoperative pain control in patients with uterovaginal prolapse undergoing vaginal hysterectomy and pelvic floor repair. We also evaluated the impact on the length of recovery. METHODS: This was a pilot study analyzing 40 women who underwent pelvic organ prolapse repair through uterosacral ligament suspension. Patients who chose to undergo PUCB were considered as cases, otherwise as controls. After general or spinal anesthesia induction, the treatment group received the PUCB with ropivacaine plus clonidine injections at 2, 4, 8, and 10 o'clock of the cervix. The control group did not receive additional treatment. Pain intensity was measured at rest and after forceful cough at 1, 4, 8, 12, 24, and 48 h postoperatively. RESULTS: We found a significant reduction in pain values at 1 h (rest and forceful cough) and 24 h (forceful cough) in the PUCB group. The incidence of moderate/severe pain was inferior in the PUCB group at 1 h (rest) and 24 h (rest and forceful cough). There were no differences in terms of the use of rescue opioids (0% vs. 5%; P = 0.311) and length of hospital stay (2.5 ± 0.6 vs. 2.3 ± 0.6; P = 0.180). CONCLUSIONS: For the first time, we demonstrated the impact of pre-emptive uterosacral/cervical block on pain control up to 24 h after surgery. Clonidine as a sensory blockade extender appears promising in enhancing the efficacy of local anesthetics.

High Uterosacral Ligaments Suspension for Post-Hysterectomy Vaginal Vault Prolapse Repair.

Background and Objectives: Uterosacral ligaments (USLs) suspension is a well-studied, safe, and long-lasting technique for central compartment correction. Preliminary clinical experiences showed encouraging data for this technique, also for post-hysterectomy vaginal vault prolapse surgical treatment. However, up-to-date evidence for post-hysterectomy vaginal vault prolapse repair through high uterosacral ligaments suspension is limited. Consequently, with this study, we aimed to assess the efficiency, complications frequency, and functional results of native-tissue repair through USLs in vaginal vault prolapse. Materials and Methods: This was a retrospective study. Women with symptomatic vaginal vault prolapse (≥stage 2) who underwent surgery with transvaginal native-tissue repair by high uterosacral ligaments were included. Patient characteristics, preoperative assessment, operative data, postoperative follow-up visits, and re-interventions were collected from the hospital's record files. High uterosacral ligament suspension was performed according to the technique previously described by Shull. A transverse apical colpotomy at the level of the post-hysterectomy scar was performed in order to enter the peritoneal cavity. USLs were identified and transfixed from ventral to dorsal with three absorbable sutures. Sutures were then passed through the vaginal apex and tightened to close the transverse colpotomy and suspend the vaginal cuff. At the end of the surgical time, a diagnostic cystoscopy was performed in order to evaluate ureteral bilateral patency. Using the POP-Q classification system, we considered an objective recurrence as the descensus of at least one compartment ≥ II stage, or the need for a subsequent surgery for POP. The complaint of bulging symptoms was considered the item to define a subjective recurrence. We employed PGI-I scores to assess patients' satisfaction. Results: Forty-seven consecutive patients corresponding to the given period were analyzed. No intraoperative complications were observed. We observed one postoperative hematoma that required surgical evacuation. Thirty-three patients completed a minimum of one-year follow-up (mean follow-up 21.7 ± 14.6 months). Objective cure rate was observed in 25 patients (75.8%). No patients required reintervention. The most frequent site of recurrence was the anterior compartment (21.2%), while apical compartment prolapse relapsed only in 6% of patients. An improvement in all POP-Q parameters was recorded except TVL which resulted in a mean 0.5 cm shorter. Subjective recurrence was referred by 4 (12.1%) patients. The mean satisfaction assessed by PGI-I score was 1.6 ± 0.8. Conclusion: This analysis demonstrated that native-tissue repair through high USL suspension is an effective and safe procedure for the treatment of post-hysterectomy vaginal vault prolapse. Objective, subjective, functional, and quality of life outcomes were satisfactory, with minimal complications.

Impact of Mannitol Bladder Distension in the Intraoperative Detection of Ureteral Kinking During Pelvic Floor Surgery.

INTRODUCTION AND HYPOTHESIS: Ureteral injuries are the most feared complications of gynecological surgery and therefore intraoperative recognition is of the utmost importance. Intraoperative cystoscopy represents the diagnostics of choice to investigate ureteral patency thanks to the direct visualization of ureteral flows after administration of infusion mediums. In this study, we aimed to compare the diagnostic performance of saline versus mannitol intraoperative cystoscopy in terms of false negatives in a large cohort of patients. METHODS: We retrospectively analyzed data of patients who underwent vaginal hysterectomy and high uterosacral ligament suspension for POP. Patients were divided in two groups based on the use of saline or mannitol medium for intraoperative cystoscopy. Postoperative daily control of serum creatinine was performed until discharge, as well as urinary tract imaging, in symptomatic patients. RESULTS: A total of 925 patients underwent vaginal hysterectomy followed by high USL suspension for POP. Saline and mannitol medium were used in 545 patients and 380 patients respectively. Postoperative ureteral injuries were identified in 12 patients, specifically in 2% of the saline group and in 0.3% of the mannitol group. CONCLUSIONS: The use of mannitol instead of saline as a bladder distension medium was able to significantly reduce the occurrence of postoperative ureteral sequelae.

Efficacy of a Diode Vaginal Laser in the Treatment of the Genitourinary Syndrome of Menopause.

INTRODUCTION: Genitourinary syndrome of menopause (GSM) and vulvovaginal atrophy (VVA) are the most frequent menopause-related clinical entities and are consistently included in the definition of pelvic floor disorders (PFDs). Nonhormonal therapies, such as lubricants and moisturizers, are indicated as first-line treatments, while the "gold standard'' is represented by topical estrogen products; however, in cancer survivors hormonal treatment is not indicated. For this reason, energy-based therapeutic approaches-for instance, through laser technologies-may be employed as alternative options in this kind of patient; however, there are no studies evaluating the efficacy of a pure diode vaginal laser in the treatment of GSM. As a consequence, with our study, we aimed to evaluate outpatient nonablative diode laser treatment in sexually active women, with contraindications, no response, or refusal of local estrogenic therapy. METHODS: This prospective study included patients with GSM, aged ≥ 18 years old, with contraindications, or refusal of local estrogen therapies. Women were evaluated via the use of their Vaginal Health Index (VHI) scores, which consists of five measures: elasticity, fluid volume, pH, epithelial integrity, and moisture. Moreover, the intensity of VVA symptoms (vaginal burning, vaginal itching, vaginal dryness, dyspareunia, and dysuria) was measured using a 10 cm visual analog scale (VAS), where the left extreme of the scale (score = 0) indicated "absence of symptom" and the right indicated "symptom as bad as it could be" (score = 100). Sexual function was evaluated with the Female Sexual Function Index (FSFI-19) questionnaire. The treatment was performed using a Leonardo Dual diode laser (Biolitec Italia Srl, Milano, Italy). The laser treatment consisted of three sessions, one per month. One month after the third session, the VHI, symptom VAS, and FSFI-19 were re-evaluated. In addition, the Patient Global Impression of Improvement (PGI-I) questionnaire was collected. RESULTS: Our study enrolled a total of 26 consecutive patients. All patients were either in menopause or under treatment with gonadotropin-releasing hormone (GnRH). None of the patients reported adverse effects after laser treatment. In total, 19 (73.1%) patients referred improvements of their symptoms according to PGI-I scores. All domains of the FSFI-19 questionnaire, significantly improved after the diode laser treatment. The mean VHI score increased by 3.2 points, from 12.2 to 15.4 (p < 0.001). Additionally, we documented a significant improvement in symptoms affecting the VAS score, from 69.2 to 43.5 points (p < 0.001). CONCLUSION: A diode vaginal laser is an effective and easily tolerated ambulatory procedure for vaginal functional restoration in the treatment of GSM and VVA.

Transvaginal excision of vaginal paraurethral leiomyoma: A video case report.

INTRODUCTION AND HYPOTHESIS: Vaginal leiomyomas are uncommon benign tumors of the genital district that appear as a circumscribed, mobile, and nontender mass along the vaginal tube. The gold standard of vaginal leiomyoma management is surgical treatment. We aimed to present a clinical case of vaginal leiomyoma successfully treated throughout a transvaginal excision and layered repair. METHODS: A 44-year-old woman was referred to our division for vaginal bulging symptoms and dyspareunia. Clinical examination revealed a 4-5 cm hard bulging mass in the anterior vaginal wall, below the urethra, compatible with vaginal leiomyoma. After proper counseling, the patient was admitted to transvaginal leiomyoma excision plus primary layered repair. RESULTS: No surgical complications were observed. The indwelling catheter was removed the day after the surgery. The patient was successfully discharged home on postoperative day 1. The patient is currently asymptomatic and there are no signs of recurrence. CONCLUSION: The procedure was successful in obtaining anatomical repair and relieving symptoms. This approach represents a valid procedure for the surgical management of this uncommon condition.

Pelvic floor ultrasound evaluation in the diagnosis of exposure of synthetic implanted materials in the lower urinary tract.

OBJECTIVE: To evaluate the diagnostic performance of pelvic floor ultrasound (PFUS) to recognize prosthetics exposure in the bladder and/or urethra in women with lower urinary tract symptoms (LUTS). METHODS: A cross-sectional study evaluating patients with LUTS after mesh/sling surgery. PFUS was performed with both transvaginal (TVUS) and translabial (TLUS) approaches. A distance of 1 mm or less from the bladder and/or urethra was considered highly suspect for mesh exposure. After PFUS, patients underwent diagnostic urethrocystoscopy. RESULTS: A total of 100 consecutive women were analyzed. According to urethrocystoscopy, the rate of tape exposure in the lower urinary tract was 3%. PFUS showed 100% sensitivity and 98%-100% specificity in detecting lower urinary tract mesh exposure. The negative predictive value was 100% and the positive predictive value ranged from 33% to 50% for urethral and 100% for bladder exposure. CONCLUSIONS: PFUS represents an effective and reliable non-invasive screening test to exclude prosthetics exposure in the bladder and/or urethra in women with LUTS.

Superinfection of Rectovaginal Endometriosis: Case Report and Review of the Literature.

BACKGROUND: A peculiar complication of endometriosis is a superinfection. However, the superinfection of extra-ovarian endometriosis is anecdotal, and only a few cases have been described. We wanted to present the first cases of the superinfection of rectovaginal endometriosis and to perform a literature review of the superinfection of extra-ovarian endometriosis. METHODS: We present a case of a 24-year-old woman who was referred to our Pelvic Floor Unit for rectal-perineal pain, dyspareunia, and recurrent episodes of dense purulent vaginal discharge for one year, in which the superinfection of rectovaginal endometriosis was diagnosed. Moreover, we performed a systematic search of the literature indexed on PubMed up to 31 January 2023. RESULTS: Laparoscopic drainage was successful in managing this condition. In the literature, clinical presentation and instrumental and microbiological findings are very heterogeneous. However, the gold standard of management is represented by surgical or percutaneous drainage. CONCLUSIONS: In the case of a pelvic abscess, the superinfection of endometriosis lesions should be suspected, and this can represent the onset symptom of endometriosis. Ultrasonography may show nodular or flat hypoechoic lesions with hyperechoic debris and peripheral positive color/power Doppler intensities. The goal of management is to drain the abscess, either percutaneously or via traditional surgery, followed by proper hormonal therapy to reduce recurrence.

Intraoperative ultrasound assessment of ureteral patency after uterosacral ligaments apical suspension for prolapse surgical repair: A feasibility study.

OBJECTIVE: To prospectively compare power Doppler ultrasound diagnostic performance with reference standard cystoscopy in evaluating ureteral patency in a population at high risk of ureteral lesions. METHODS: We analyzed 100 women who underwent pelvic organ prolapse repair. All ultrasound scans were obtained, at the end of the procedures, before cystoscopic evaluation. Bilateral simultaneous ureteral jet evaluation with power Doppler was performed at the level of the ureterovesical junctions with a pulse repetition frequency set to detect low flow for a maximum of 3 min. RESULTS: According to the reference standard urethrocystoscopy, at least one ureter not ejaculating was observed in 6% of patients, for a total of seven ureters jets not visualized. No false-negative results were obtained. Ultrasound with power Doppler showed 100% sensitivity and 95.9% specificity in detecting the lack of ureteral jet. The negative predictive value was 100%, and the positive predictive value was 46.7%. CONCLUSIONS: Ultrasound with power Doppler represents an effective and reliable non-invasive screening test to exclude ureteral kinking and reduce the need for intraoperative cystoscopy.

Prevalence and severity of lower urinary tract symptoms in the third trimester of pregnancy.

INTRODUCTION AND HYPOTHESIS: Pregnancy is a risk factor for urinary disorders, mainly in the third trimester. Lower urinary tract symptoms (LUTS) are often underreported by health care professionals and significantly impact the quality of life of pregnant women. Our objective is to analyse lower urinary tract function during the third trimester of pregnancy and assess the impact of traditional risk factors for pelvic floor dysfunctions on bladder health in pregnant women. METHODS: This is a secondary analysis of a multicentre cross-sectional study. Third-trimester pregnant women aged 18 years or older anonymously filled in the "Italian Pelvic Floor Questionnaire for pregnant and postpartum women" questionnaire, validated for pelvic floor disorders in pregnancy and postpartum. RESULTS: A total of 927 pregnant patients completed the questionnaire. Among them, 97.3% complained of at least one urinary disorder. Frequency was the symptom reported most often (77.3%), whereas nocturnal enuresis was the least reported (17%). Despite the high prevalence of LUTS in our sample, only 13.4% reported that they negatively impact their quality of life. Overweight and obesity, advanced maternal age, smoking, family history of pelvic floor disorders and poor pelvic floor contraction capacity were confirmed to be risk factors for the onset of LUTS, even in our population. CONCLUSIONS: Urinary symptoms are extremely common in the third trimester and significantly affect the quality of life of pregnant women. Since overweight, obesity, smoking and reduced pelvic floor contractility emerged as modifiable risk factors for the development of these symptoms, prevention and adequate counselling are cornerstones of pregnancy care.

Prevalence and Severity of Pelvic Floor Disorders during Pregnancy: Does the Trimester Make a Difference?

(1) Background: Women experience pelvic floor dysfunction symptoms during pregnancy. This study is the first to investigate and compare variances in the prevalence and severity of pelvic floor symptoms between trimesters using a valid pregnancy-targeted questionnaire. (2) Methods: A retrospective cohort study was conducted between August 2020 to January 2021 at two university-affiliated tertiary medical centers. Pregnant women (n = 306) anonymously completed the Pelvic Floor Questionnaire for Pregnancy and Postpartum with its four domains (bladder, bowel, prolapse, and sexual). (3) Results: Thirty-six women (11.7%) were in the 1st trimester, eighty-three (27.1%) were in the 2nd trimester, and one hundred and eighty-seven (61.1%) were in the 3rd trimester. The groups were similar in age, pregestational weight, and smoking habits. A total of 104 (34%) had bladder dysfunction, 112 (36.3%) had bowel dysfunction, and 132 (40.4%) reported sexual inactivity and/or sexual dysfunction. Least prevalent (33/306; 10.8%) were prolapse symptoms. Increased awareness of prolapse and significantly higher rates of nocturia and the need to use pads due to incontinence were recorded in the 3rd trimester. Sexual dysfunction or abstinence were equally distributed in all three trimesters. (4) Conclusions: Bladder and prolapse symptoms, equally frequent throughout pregnancy, significantly intensified in the 3rd trimester. Bowel and sexual symptoms, equally frequent throughout pregnancy, did not intensify in the third trimester.

Flat Magnetic Stimulation for Stress Urinary Incontinence: A Prospective Comparison Study.

BACKGROUND: Flat Magnetic Stimulation (FMS) is characterized by a stimulation generated by electromagnetic fields with a homogenous profile. One possible application is the treatment of stress urinary incontinence (SUI). We aimed to compare the objective, subjective, quality of life, and instrumental outcomes in women with SUI not eligible for surgery undergoing either FMS or pelvic floor muscle training (PFMT). METHODS: This was a prospective interventional study. After proper counseling, patients with isolated SUI were divided according to their treatment of choice into FMS and PFMT groups. At baseline and after treatment, patients completed the International Consultation on Incontinence Questionnaire-Short Form, the Female Sexual Function Index, and the Incontinence Impact Questionnaire, and volumetric measurement of the urethral rhabdosphincter (RS) was performed. The Patient Global Impression of Improvement questionnaire and stress test defined subjective and objective cure rates, respectively. RESULTS: We observed improvements in urinary-related quality of life scores and an increase in RS volume after FMS compared to baseline. All these outcomes were significantly better compared to women who underwent PFMT. CONCLUSION: Our study demonstrated that FMS is a safe and effective conservative option for SUI management in terms of objective and subjective cure rates.

Surgical management of rectovaginal fistula after stapled transanal rectal resection for prolapsed hemorrhoids.

INTRODUCTION AND HYPOTHESIS: Rectovaginal fistula is an epithelium-lined direct communication route between the vagina and the rectum. The gold standard of fistula management is surgical treatment. Rectovaginal fistula after stapled transanal rectal resection (STARR) may be challenging to treat, due to the extensive scarring, the local ischemia, and the risk of rectal stenosis. We aimed to present a case of iatrogenic rectovaginal fistula after STARR that was successfully treated with a transvaginal primary layered repair and bowel diversion. METHODS: A 38-year-old woman was referred to our division for continuous fecal discharge through her vagina that developed a few days after she had a STARR for prolapsed hemorrhoids. Clinical examination revealed a 2.5 cm-wide direct communication between the vagina and rectum. After proper counseling, the patient was admitted to transvaginal layered repair and temporary laparoscopic bowel diversion RESULTS: No surgical complications were observed. The patient was successfully discharged home on postoperative day 3. Bowel diversion was reversed after 2 months. At the current follow-up (6 months), the patient is asymptomatic and without recurrence. CONCLUSIONS: The procedure was successful in obtaining anatomical repair and relieving symptoms. This approach represents a valid procedure for the surgical management of this severe condition.

Mesenchymal Stem Cells Sense the Toughness of Nanomaterials and Interfaces.

Stem cells are known to sense and respond to the mechanical properties of biomaterials. In turn, cells exert forces on their environment that can lead to striking changes in shape, size and contraction of associated tissues, and may result in mechanical disruption and functional failure. However, no study has so far correlated stem cell phenotype and biomaterials toughness. Indeed, disentangling toughness-mediated cell response from other mechanosensing processes has remained elusive as it is particularly challenging to uncouple Youngs' or shear moduli from toughness, within a range relevant to cell-generated forces. In this report, it is shown how the design of the macromolecular architecture of polymer nanosheets regulates interfacial toughness, independently of interfacial shear storage modulus, and how this controls the expansion of mesenchymal stem cells at liquid interfaces. The viscoelasticity and toughness of poly(l-lysine) nanosheets assembled at liquid-liquid interfaces is characterised via interfacial shear rheology. The local (microscale) mechanics of nanosheets are characterised via magnetic tweezer-assisted interfacial microrheology and the thickness of these assemblies is determined from in situ ellipsometry. Finally, the response of mesenchymal stem cells to adhesion and culture at corresponding interfaces is investigated via immunostaining and confocal microscopy.

Risk of Premature Ovarian Insufficiency after Human Papilloma Virus Vaccination: A PRISMA Systematic Review and Meta-Analysis of Current Evidence.

(1) Background: Premature ovarian insufficiency (POI) has been linked to human papilloma virus (HPV) vaccination in small case-reports. The aim of this meta-analysis was to evaluate the risk of POI after HPV vaccination. (2) Methods: Electronic searches in MEDLINE Scopus, LILACS, ClinicalTrials.gov, EMBASE, PROSPERO, Cochrane CENTRAL and other registries were searched from inception to September 2022. Inclusion criteria were cohort studies of female children or adolescents vaccinated with quadrivalent (4vHPV), bivalent (2vHPV) or 9-valent (9vHPV) vaccine and compared to unvaccinated, other HPV vaccine, or vaccinated with other childhood vaccine girls. Primary outcome was risk of POI after vaccination. (3) Results: Four studies, including 1,253,758 patients, were included. Overall, there was no significant risk for POI between 4vHPV and controls (unvaccinated or other vaccines) (RR 0.47 (95% CI 0.14 to 1.59) I2 = 75%), or unvaccinated only controls (RR 0.75 (95% CI 0.22 to 2.49) I2 = 26%). One study reported a significant reduction of POI risk for 4vHPV relative to the other childhood vaccinations (RR 0.03 (95% CI 0.00 to 0.21)); meanwhile, one study showed no increased risk with 4vHPV relative to 2vHPV and 9vHPV (RR 0.93 (95% CI 0.33 to 2.64)). (4) Conclusions: 4vHPV vaccination does not seem to increase risk of POI relative to unvaccinated people or other childhood vaccines. No difference was seen with 4vHPV vaccine relative to 2vHPV and 9vHPV. Moreover, the risk of POI after HPV vaccination is relatable to worldwide incidence, giving reassurance about safety.

Coexisting overactive-underactive bladder and detrusor overactivity-underactivity in pelvic organ prolapse.

OBJECTIVE: The coexisting overactive-underactive bladder (COUB) syndrome could be related to the increased urethral resistance caused by severe pelvic organ prolapse (POP). We aimed to evaluate the clinical and urodynamic findings of patients with COUB and/or detrusor overactivity-underactivity (DOU) in a cohort of patients scheduled for POP surgery and the possible risk factors of COUB after surgery. METHODS: This retrospective study analyzed all patients who underwent POP repair between 2008 and 2013, excluding women with a history of pelvic floor surgery. Patients were divided into COUB and non-COUB according to baseline symptoms and into DOU and non-DOU based on urodynamic findings. A multivariate model was performed to identify risk factors for COUB symptoms after surgery. RESULTS: A total of 533 women underwent POP surgery. Preoperatively, patients with COUB had more severe anterior compartment prolapse (Pelvic Organ Prolapse Quantification staging system Aa point, P = 0.008) and more frequently had overactive bladder compared with controls (P = 0.023). The rate of COUB decreased significantly after surgery. Preoperative opening detrusor pressure resulted as the only independent predictor of postoperative COUB symptoms (P = 0.034). CONCLUSION: POP is a valid pathogenetic model for COUB development. POP repair induced a significant decrease in COUB symptoms with low opening detrusor pressure resulting as the only independent predictor of postoperative COUB.