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Introduction: Urinary incontinence is a common complaint of both general practitioners and specialists. An accurate basic diagnosis with a structured medical history and bladder diary, urine analysis, gynaecological examination including pelvic floor assessment and a full bladder cough test can be supplemented by sonography, cystoscopy and urodynamic testing. This will help to differentiate between the different types of urinary incontinence, such as urge incontinence, stress incontinence and overflow incontinence. Treatment should be based on the type of urinary incontinence. Conservative treatments such as pelvic floor physiotherapy and pessaries can be supplemented by electrical stimulation for OAB and overflow incontinence, and various procedures such as TVT or bulking agents for stress incontinence, sacral neurostimulation for OAB and overflow incontinence., Competing Interests: Die Autorinnen und Autoren haben keine Interessenkonflikte im Zusammenhang mit diesem Artikel deklariert., (© 2024 Aerzteverlag medinfo AG.)

Background: Genital pain treatment regimens range from local or systemic pharmacological to non-pharmacological, manual and psychosexual therapies with poor to moderate evidence for their efficiency. The aim of this study was to evaluate the subjective therapeutic response (genital pain relief) of different treatment modalities for vulvodynia and the most prevalent other vulvar pathologies, chronic vulvar eczema and lichen sclerosus by means of a cross-sectional survey., Material and Methods: A questionnaire-based cohort study that included 128 vulvodynia, 116 eczema and 79 lichen sclerosus patients was used. All patients attended the vulvar clinic at the University Hospital of Zurich. The patients who had been treated were surveyed from January to October 2022, using a customized online questionnaire consisting of 37 questions on symptoms and treatment outcomes for guideline-recommended treatment modalities. The study was approved by the Cantonal Ethics Review Board of Zurich., Results: Altogether, 41 patients with vulvodynia, 37 with vulvar eczema and 23 with lichen sclerosus returned the questionnaire. The three groups were similar regarding pain characteristics and comorbidities. All three patient groups reported having benefited from non-pharmacological treatment (improvement rate vulvodynia 54%; eczema 51%; lichen sclerosus 58%), from topical (55%; 55%; 75%) and from locally invasive (46%; 66%; 50%) treatments. Overall, there was no significant difference in subjective treatment outcome between non-pharmacological, locally invasive, and topical treatments for vulvodynia, eczema, and lichen sclerosus. However, the use of oral medication was reported to be significantly less effective (p-value 0.050)., Conclusion: In conclusion, we found that in the patients' perception, topical, invasive and non-pharmacological treatments, but not oral medications, are helpful for genital pain relief in women with vulvodynia, vulvar eczema, and lichen sclerosus. Therefore, we recommend an escalating therapy approach with first-line non-pharmacological treatments together with topical therapies., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Berger et al.)

Purpose: To define the normal range and threshold values for pathologic prolapse on MRI using the PICS line and assess its correlation with the pubococcygeal line (PCL)., Methods: This prospective, IRB-approved study included 20 nulliparous volunteers and 18 prolapse patients (POP-Q Stage ≥ 2). Organ positions (bladder, cervix, anorectal junction) relative to PICS and PCL were measured on dynamic MRI. Differences in organ position were compared. Receiver-operating characteristic (ROC) analysis was performed to identify cutoff values for prolapse using the PICS line. The correlation between PICS and PCL measurements was tested with Spearman's rank correlation., Results: In volunteers, median bladder and cervix positions measured to the PICS at rest were - 2.7 cm and - 5.3 cm compared to - 1.9 cm and - 2.7 cm in patients (p < 0.001). During straining, bladder and cervix were at - 0.9 cm and - 3.2 cm in volunteers versus + 2.5 cm and + 2.5 cm in patients (p < 0.001). Correlation was strong for PICS and PCL measurements for all three compartments (δ = 0.883-0.970, p ≤ 0.001). AUCs of PICS for the anterior and middle compartment were 0.98 (95% confidence interval [CI] 0.96-1.00, p < 0.001) and 0.96 (95% CI 0.89-1.00, p < 0.001) for differentiating patients from healthy volunteers. AUC for the posterior compartment was 0.76 (95% CI 0.57-0.96, p = 0.034)., Conclusion: PICS measurements reliably differentiate patients from volunteers in the anterior and middle compartment. Future studies need to identify a reliable threshold for the posterior compartment. PICS and PCL measurements are strongly correlated., (© 2024. The Author(s).)

Background: The levator ani muscle (LAM) is crucial for pelvic floor stability, yet its quantitative MRI assessment is only a recent focus. Our study aims to standardize the quantitative analysis of the LAM morphology within the 3D Pelvic Inclination Correction System (3D-PICS)., Methods: We analyzed 35 static MR datasets from nulliparous women examining the pubovisceral (PVM), iliococcygeal (ICM), coccygeal (COC), and puborectal muscle (PRM). The PVM consists of three origin-insertion pairs, namely the puboanal (PAM), puboperineal (PPM) and pubovaginal muscle (PVaM). The analysis included a quantitative examination of the morphology of LAM, focusing on the median location (x/y/z) (x: anterior-posterior, y: superior-inferior, z: left-right) of the origin and insertion points (a), angles (b) and lengths (c) of LAM. Inter-rater reliability was calculated., Results: Interindividual variations in 3D coordinates among muscle subdivisions were shown. In all, 93% of all origin and insertion points were found within an SD of <8 mm. Angles to the xz-plane range between -15.4° (right PRM) and 40.7° (left PAM). The PRM is the largest pelvic muscle in static MRI. The ICC indicated moderate-to-good agreement between raters., Conclusions: The accurate morphometry of the LAM and its subdivisions, along with reliable inter-rater agreement, was demonstrated, enhancing the understanding of normal pelvic anatomy in young nulliparous women.

The genitourinary syndrome of menopause (GSM) affects up to 84% of postmenopausal women and may significantly reduce the quality of life in some. For symptom relief, there are several non-hormonal and hormonal vaginal products available. In Europe, vaginal estriol (E3) is the most frequently chosen estrogen for GSM treatment. The aim of this systematic review was to assess the impact of vaginal E3 on serum sex hormone levels, an outcome that has been previously used to assess safety in similar products. In our review, we did not find any alterations in serum estrone, estradiol, testosterone, progesterone and sex hormone binding globulin levels after vaginal E3 application. In contrast, some studies showed a minimal and transient decrease in serum gonadotropin levels, which however remained within the postmenopausal range. Similarly, only a few studies reported a minimal and transient increase of serum E3 levels, with the rest reporting no changes. The lack of clinically relevant long-term changes in serum sex hormone levels supports the current literature providing evidence about the safety of vaginal E3 products.

Purpose: The aim of the MRI-study was to evaluate the visibility of the pelvic floor ligaments and to analyze the ligament morphometry in 3D space., Methods: Twenty-two nulliparous women underwent MRI with a ligament specific protocol. MR datasets were evaluated using the 3D Pelvic Inclination Correction System (3D-PICS). The round ligament (RL), sacrospinous ligament (SSL), sacrotuberous ligament (STL), urogenital diaphragm (UGD) and uterosacral ligament (USL) were analyzed. Qualitative and quantitative analysis was performed. 3D coordinates for origin and insertion points were determined relative to the symphysis; subsequently lengths and angles were calculated. Interrater reliability was calculated to validate the point determination method., Results: Moderate to good visibility was reported for the RL, the SSL, the STL and the UGD. Standard deviation of the points analyzed in the different dimensions vary from 1.5 mm to 21.3 mm. Origin and insertion points of the ligaments are found within a mean standard distance of 10.7 mm. The highest variability was seen in insertion points of RL, with a standard distance of 25.4 mm. The interrater reliability was good to very good (range of intraclass correlation coefficients (ICC) from 0.58 to 0.96), except for the UGD ventral points (ICC from 0.27 to 0.55)., Conclusions: This in-vivo MRI technique development study offers first exact data describing the pelvic floor ligaments in nulliparous women in 3D-PICS. Visibility, exact 3D coordinates of the origin and insertion points, lengths, angles and interrater reliability assessed for all parameters were evaluated morphometrically., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Dysmenorrhea affects women throughout their reproductive years but there has been a lack of effective and well-tolerated treatment options. Pain symptoms mainly result from inflammatory processes and increased contractile activity in the myometrium. The reported use of Bryophyllum pinnatum preparations against inflammation and pain in ethnomedicine as well as current pharmacological data on their inhibition of myometrial contractility led us to hypothesize that this medicinal plant might be a new treatment option for dysmenorrhea. In the first part of the present work, clinical, in vivo, and in vitro studies on the anti-nociceptive and anti-inflammatory, as well as on myometrium relaxing properties of B. pinnatum are reviewed. In the second part, cases of five women with dysmenorrhea who were tentatively treated with a B. pinnatum product are described. The review revealed thirty-three experimental in vivo and in vitro studies, but no clinical study, reporting anti-nociceptive and anti-inflammatory effects of B. pinnatum extracts and compounds in a wide range of conditions. Moreover, sixteen publications on smooth muscle contractility revealed relaxing effects. The latter consisted of clinical evidence, as well as of in vivo and in vitro data. The evidence reviewed therefore provided a rational basis for the use of B. pinnatum in the treatment of dysmenorrhea. We subsequently set out to tentatively treat patients with a well-tolerated B. pinnatum product that is registered (without indication) and commonly used in obstetrics and gynecology in Switzerland. All five treated patients reported a reduction in pain symptoms and 4 out of 5 indicated a reduced intake of painkillers during menstruation. Taken together, the reviewed information on the pharmacological properties and clinical evidence of B. pinnatum extracts and compounds as well as the outcomes of all five patients in the case series support our hypothesis in favor of B. pinnatum as a new, well-tolerated therapeutic approach for dysmenorrhea. Prospective clinical studies are urgently needed., Competing Interests: MS is employed by Praxis Geburt and Familie, Dr. med. Werner Stadlmayr GmbH, Aarau, Switzerland. APS-W has received research funding from Weleda AG over the last 5 years. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zurfluh, Spinelli, Betschart and Simões-Wüst.)

Clinical/methodical Issue: Pelvic organ prolapse is a common condition in women, for which both conservative and surgical interventions are available. Knowledge of the different surgical procedures and the materials used is essential for adequate radiological diagnosis after prolapse surgery in order to differentiate potential complications from normal postoperative changes., Standard Radiological Methods: In the immediate postoperative period, computed tomography (CT) is often the modality of choice for evaluating acute complications such as bleeding or organ injuries. Magnetic resonance imaging (MRI) provides excellent soft tissue contrast and is therefore generally preferred for assessing subacute and chronic complications., Methodical Innovations: Innovative techniques such as dynamic MRI protocols can improve the radiological assessment after prolapse surgery by enabling the evaluation of organ mobility., Performance: Radiological standard procedures such as computed tomography (CT) and MRI provide detailed and reliable information about the postoperative site and potential complications following prolapse surgery., Achievements: Radiological imaging plays an important role in the evaluation of patients after prolapse surgery, particularly when complications are suspected. Accurate radiological diagnosis can guide further appropriate therapeutic measures., (© 2023. The Author(s).)

Introduction and Hypothesis: The purpose was to investigate the safety and feasibility of transurethral injections of autologous muscle precursor cells (MPCs) into the external urinary sphincter (EUS) to treat stress urinary incontinence (SUI) in female patients., Methods: Prospective and randomised phase I clinical trial. Standardised 1-h pad test, International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), urodynamic study, and MRI of the pelvis were performed at baseline and 6 months after treatment. MPCs gained through open muscle biopsy were transported to a GMP facility for processing and cell expansion. The final product was injected into the EUS via a transurethral ultrasound-guided route. Primary outcomes were defined as any adverse events (AEs) during follow-up. Secondary outcomes were functional, questionnaire, and radiological results., Results: Ten female patients with SUI grades I-II were included in the study and 9 received treatment. Out of 8 AEs, 3 (37.5%) were potentially related to treatment and treated conservatively: 1 urinary tract infection healed with antibiotics treatment, 1 dysuria and 1 discomfort at biopsy site. Functional urethral length under stress was 25 mm at baseline compared with 30 mm at 6 months' follow-up (p=0.009). ICIQ-UI-SF scores improved from 7 points at baseline to 4 points at follow-up (p=0.035). MRI of the pelvis revealed no evidence of tumour or necrosis, whereas the diameter of the EUS muscle increased from 1.8 mm at baseline to 1.9 mm at follow-up (p=0.009)., Conclusion: Transurethral injections of autologous MPCs into the EUS for treatment of SUI in female patients can be regarded as safe and feasible. Only a minimal number of expected and easily treatable AEs were documented., (© 2023. The Author(s).)

Purpose: To compare multi-slice (MS) MRI sequences of the pelvis acquired at rest and straining to dynamic midsagittal single-slice (SS) sequences for the assessment of pelvic organ prolapse (POP)., Methods: This IRB-approved prospective single-center feasibility study included 23 premenopausal symptomatic patients with POP and 22 asymptomatic nulliparous volunteers. MRI of the pelvis at rest and straining was performed with midsagittal SS and MS sequences. Straining effort, visibility of organs and POP grade were scored on both. Organ points (bladder, cervix, anorectum) were measured. Differences between SS and MS sequences were compared with Wilcoxon test., Results: Straining effort was good in 84.4% on SS and in 64.4% on MS sequences (p = 0.003). Organ points were always visible on MS sequences, whereas the cervix was not fully visible in 31.1-33.3% on SS sequences. At rest, there were no statistically significant differences of organ point measurements between SS and MS sequences in symptomatic patients. At straining, positions of bladder, cervix, and anorectum were + 1.1 cm (± 1.8 cm), - 0.7 cm (± 2.9 cm), and + 0.7 cm (± 1.3 cm) on SS and + 0.4 mm (± 1.7 cm), - 1.4 cm (± 2.6 cm), and + 0.4 cm (± 1.3 cm) on MS sequences (p < 0.05). Only 2 cases of higher-grade POP were missed on MS sequences (both with poor straining effort)., Conclusion: MS sequences increase the visibility of organ points compared to SS sequences. Dynamic MS sequences can depict POP if images are acquired with sufficient straining effort. Further work is needed to optimize the depiction of the maximum straining effort with MS sequences., (© 2023. The Author(s).)

Toll-like receptor (TLR) 7 and TLR8 are endosomal sensors of the innate immune system that are activated by GU-rich single stranded RNA (ssRNA). Multiple genetic and functional lines of evidence link chronic activation of TLR7/8 to the pathogenesis of systemic autoimmune diseases (sAID) such as Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE). This makes targeting TLR7/8-induced inflammation with small-molecule inhibitors an attractive approach for the treatment of patients suffering from systemic autoimmune diseases. Here, we describe how structure-based optimization of compound 2 resulted in the discovery of 34 (MHV370, ( S )-N-(4-((5-(1,6-dimethyl-1 H -pyrazolo[3,4- b ]pyridin-4-yl)-3-methyl-4,5,6,7-tetrahydro-1 H -pyrazolo[4,3- c ]pyridin-1-yl)methyl)bicyclo[2.2.2]octan-1-yl)morpholine-3-carboxamide). Its in vivo activity allows for further profiling toward clinical trials in patients with autoimmune disorders, and a Phase 2 proof of concept study of MHV370 has been initiated, testing its safety and efficacy in patients with Sjögren's syndrome and mixed connective tissue disease., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Background: Robotic surgery has gained popularity for the reconstruction of pelvic floor defects. Nonetheless, there is no evidence that robot-assisted reconstructive surgery is either appropriate or superior to standard laparoscopy for the performance of pelvic floor reconstructive procedures or that it is sustainable. The aim of this project was to address the proper role of robotic pelvic floor reconstructive procedures using expert opinion., Methods: We set up an international, multidisciplinary group of 26 experts to participate in a Delphi process on robotics as applied to pelvic floor reconstructive surgery. The group comprised urogynecologists, urologists, and colorectal surgeons with long-term experience in the performance of pelvic floor reconstructive procedures and with the use of the robot, who were identified primarily based on peer-reviewed publications. Two rounds of the Delphi process were conducted. The first included 63 statements pertaining to surgeons' characteristics, general questions, indications, surgical technique, and future-oriented questions. A second round including 20 statements was used to reassess those statements where borderline agreement was obtained during the first round. The final step consisted of a face-to-face meeting with all participants to present and discuss the results of the analysis., Results: The 26 experts agreed that robotics is a suitable indication for pelvic floor reconstructive surgery because of the significant technical advantages that it confers relative to standard laparoscopy. Experts considered these advantages particularly important for the execution of complex reconstructive procedures, although the benefits can be found also during less challenging cases. The experts considered the robot safe and effective for pelvic floor reconstruction and generally thought that the additional costs are offset by the increased surgical efficacy., Conclusion: Robotics is a suitable choice for pelvic reconstruction, but this Delphi initiative calls for more research to objectively assess the specific settings where robotic surgery would provide the most benefit., (© 2023. The Author(s).)

Genetic and in vivo evidence suggests that aberrant recognition of RNA-containing autoantigens by Toll-like receptors (TLRs) 7 and 8 drives autoimmune diseases. Here we report on the preclinical characterization of MHV370, a selective oral TLR7/8 inhibitor. In vitro, MHV370 inhibits TLR7/8-dependent production of cytokines in human and mouse cells, notably interferon-α, a clinically validated driver of autoimmune diseases. Moreover, MHV370 abrogates B cell, plasmacytoid dendritic cell, monocyte, and neutrophil responses downstream of TLR7/8. In vivo, prophylactic or therapeutic administration of MHV370 blocks secretion of TLR7 responses, including cytokine secretion, B cell activation, and gene expression of, e.g., interferon-stimulated genes. In the NZB/W F1 mouse model of lupus, MHV370 halts disease. Unlike hydroxychloroquine, MHV370 potently blocks interferon responses triggered by specific immune complexes from systemic lupus erythematosus patient sera, suggesting differentiation from clinical standard of care. These data support advancement of MHV370 to an ongoing phase 2 clinical trial., Competing Interests: Declaration of interests All authors except S.A., B.B., H.I.B., J.D., D.K., P.M., F.R., and J.S.R. are current employees and shareholders of Novartis Pharma AG. MHV370 is described in patent WO2018047081., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Nocturia is a pathologic condition that significantly affects the quality of sleep. The aetiology of nocturia is multifactorial, and the evidence available on its management remains limited. Besides behavioural measures, validated pharmaceutical treatment options exist but are, however, associated with marked side effects. Prospective clinical studies with tablets prepared from the leaf press juice of the plant Bryophyllum pinnatum revealed a tendency towards reduction of micturition in patients with overactive bladder (OAB) and several improvements in sleep quality. These observations are in part supported by in vitro and in vivo data. In the present study, we investigated the effectiveness of Bryophyllum 50% chewable tablets in the treatment of nocturia and associated sleep disorders. Altogether, 49 women with idiopathic OAB and nocturia of ≥2 voids/night were treated with Bryophyllum 50% tablets for 3 weeks (350 mg chewable tablets, dosage 0-0-2-2 oral tablets; WELEDA AG, Arlesheim, Switzerland). Nocturia, voiding volumes at night (ml), quality of life, sleep quality, and daily sleepiness were assessed before and after treatment with a 3-day micturition diary, the International Consultation on Incontinence evaluating overactive bladder and related impact on quality of life (QoL) [ICIQ-OAB], the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS), respectively. The age of the study population was 68.5 ± 11.6 y. After treatment, nocturia diminished from 3.2 ± 1.4 to 2.3 ± 1.3 ( P   <  0.001) and the PSQI score decreased from 7.7 ± 3.7 to 6.6 ± 3.4 ( P =0.004). Urgency, the ICIQ score, and the ESS lowered significantly, and the micturition volume showed a tendency to increase. No serious adverse drug reactions were reported, and compliance was good. The results show a beneficial effect on the nocturnal voids and sleep quality of women with OAB. Bryophyllum 50% tablets can be regarded as a well-tolerated alternative in the treatment of nocturia and broaden the repertoire of standard management., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 Nurlana Mirzayeva et al.)

Aim This completely revised interdisciplinary S2k-guideline on the diagnosis, therapy, and follow-up care of female patients with urinary incontinence (AWMF registry number: 015-091) was published in December 2021. This guideline combines and summarizes earlier guidelines such as "Female stress urinary incontinence," "Female urge incontinence" and "Use of Ultrasonography in Urogynecological Diagnostics" for the first time. The guideline was coordinated by the German Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group for Urogynecology and Plastic Pelvic Floor Reconstruction (Arbeitsgemeinschaft für Urogynäkologie und plastische Beckenbodenrekonstruktion e. V., AGUB). Methods This S2k-guideline was developed using a structured consensus process involving representative members from different medical specialties and was commissioned by the Guidelines Commission of the DGGG, OEGGG and SGGG. The guideline is based on the current version of the guideline "Urinary Incontinence in Adults" published by the European Association of Urology (EAU). Country-specific items associated with the respective healthcare systems in Germany, Austria and Switzerland were also incorporated. Recommendations The short version of this guideline consists of recommendations and statements on the surgical treatment of female patients with stress urinary incontinence and urge incontinence. Specific solutions for the diagnostic workup and treatment of uncomplicated and complicated urinary incontinence are discussed. The diagnostics and surgical treatment of iatrogenic urogenital fistula are presented., Competing Interests: Conflict of Interest The conflicts of interest of the authors are listed in the long version of the guideline ( https://register.awmf.org/de/leitlinien/detail/015-091 )./ Die Interessenkonflikte der Autoren sind in der Langfassung der Leitlinie ( https://register.awmf.org/de/leitlinien/detail/015-091 ) aufgelistet., (Thieme. All rights reserved.)

Aim This completely revised interdisciplinary S2k-guideline on the diagnosis, therapy, and follow-up care of female patients with urinary incontinence (AWMF registry number: 015-091) was published in December 2021. This guideline combines and summarizes earlier guidelines such as "Female stress urinary incontinence," "Female urge incontinence" and "Use of Ultrasonography in Urogynecological Diagnostics" for the first time. The guideline was coordinated by the German Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group for Urogynecology and Plastic Pelvic Floor Reconstruction (Arbeitsgemeinschaft für Urogynäkologie und plastische Beckenbodenrekonstruktion e. V., AGUB). Methods This S2k-guideline was developed using a structured consensus process involving representative members from different medical specialties and was commissioned by the Guidelines Commission of the DGGG, OEGGG and SGGG. The guideline is based on the current version of the guideline "Urinary Incontinence in Adults" published by the European Association of Urology (EAU). Country-specific items associated with the respective healthcare systems in Germany, Austria and Switzerland were also incorporated. Recommendations The short version of this guideline consists of recommendations and statements on the epidemiology, etiology, classification, symptoms, diagnostics, and treatment of female patients with urinary incontinence. Specific solutions for the diagnostic workup and appropriate conservative and medical therapies for uncomplicated and complication urinary incontinence are discussed., Competing Interests: Conflict of Interest The conflicts of interest of all the authors are listed in the long version of the guideline ( https://register.awmf.org/de/leitlinien/detail/015-091 )./ Die Interessenkonflikte der Autoren sind in der Langfassung der Leitlinie ( https://register.awmf.org/de/leitlinien/detail/015-091 ) aufgelistet., (Thieme. All rights reserved.)

The uterine suspensory tissue (UST) complex includes the cardinal (CL) and uterosacral "ligaments" (USL), which are mesentery-like structures that play a role in resisting pelvic organ prolapse (POP). Since there is no information on the time-dependent material properties of the whole structure in situ and in vivo, we developed and tested an intraoperative technique to quantify in vivo whether there is a significant difference in visco-hyperelastic behavior of the CL and USL between women with and without POP. Thirteen women with POP (cases) and four controls scheduled for surgery were selected from an ongoing POP study. Immediately prior to surgery, a computer-controlled linear servo-actuator with a series force transducer applied a continuous, caudally directed traction force while simultaneously recording the resulting cervical displacement in the same direction. After applying an initial 1.1 N preload, a ramp rate of 4 mm/s was used to apply a maximum force of 17.8 N in three "ramp-and-hold" test trials. A simplified bilateral four-cable biomechanical model was used to identify the material behavior of each ligament. For this, the initial cross-section areas of the CL and USL were measured on 3-T magnetic resonance image-based 3D models from each subject. The time-dependent strain energy function of CL/USL was defined with a three-parameter hyperelastic Mooney-Rivlin material model and a two-term Prony series in relaxation form. When cases were compared with controls, the estimated time-dependent material constants of CL and USL did not differ significantly. These are the first measurements that compare the in vivo and in situ visco-hyperelastic response of the tissues comprising the CL and USL to loading in women with and without prolapse. Larger sample sizes would help improve the precision of intergroup differences., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Given the high variation of perceptions of women with stress urinary incontinence (SUI), qualitative meta-synthesis in this field appears warranted. We aimed to synthesize evidence on women's experiences of SUI by analyzing qualitative data., Methods: A literature search of Medline, Embase, Scopus, PsycInfo, and CINAHL databases was performed by a CHORUS Working Group, from inception to August 2020. Qualitative studies on women's perspectives on SUI were included. Thematic analysis was used as a conceptual approach to analyze the data and develop a set of overarching themes. The quality of studies was assessed based on the Critical Appraisal Skills Program tool., Results: Seven studies were included. Six themes encompassing women's perspectives on SUI emerged: experiencing SUI, awareness of SUI, treatments for SUI, sexuality, communication, and psychosocial effects. The quality appraisal of the studies showed good coherence., Conclusion: This study revealed six overarching themes, of which treatment had the highest prevalence. Assessment of women's perceptions of SUI in the context of a qualitative meta-synthesis may inform policy and practice around this condition, may guide and help set research priorities, and will ideally contribute to the development of a Core Outcome Set for SUI., (© 2021 International Federation of Gynecology and Obstetrics.)

Introduction and Hypothesis: Evidence on OAB management remains suboptimal and methodological limitations in randomized control trials (RCTs) affect their comparability. High quality meta-analyses are lacking. This study aimed to compare selection and reporting of outcomes and outcome measures across RCTs as well as evaluate methodological quality and outcome reporting quality as a first stage in the process of developing core outcome sets (COS)., Methods: RCTs were searched using Pubmed, EMBASE, Medline, Cochrane, ICTRP and Clinicaltrials.gov from inception to January 2020, in English language, on adult women. Pharmacological management, interventions, sample size, journal type and commercial funding were documented. Methodological and outcome reporting quality were evaluated using JADAD and MOMENT scores., Results: Thirty-eight trials (18,316 women) were included. Sixty-nine outcomes were reported, using 62 outcome measures. The most commonly reported outcome domains were efficacy (86.8%), safety (73.7%) and QoL (60.5%). The most commonly reported outcomes in each domain were urgency urinary incontinence episodes (UUI) (52.6%), antimuscarinic side effects (76.3%) and change in validated questionnaire scores (36.8%). A statistically significant correlation was found between JADAD and MOMENT (Spearman's rho = 0.548, p < 0.05) scores. This indicates that higher methodological quality is associated with higher outcome reporting quality., Conclusions: Development of COS and core outcome measure sets will address variations and lead to higher quality evidence. We recommend the most commonly reported outcomes in each domain, as interim COS. For efficacy we recommend: UUI episodes, urgency and nocturia episodes; for safety: antimuscarinic adverse events, other adverse events and discontinuation rates; for QoL: OAB-q, PPBC and IIQ scores., (© 2022. The Author(s).)

Introduction and Hypothesis: To assess the long-term satisfaction, cure rate and safety of a new titanium-covered transobturator tape compared to polypropylene tape for the treatment of stress urinary incontinence (SUI)., Methods: A prospective study was conducted with 151 patients. Seventy patients underwent transobturator sling surgery with titanium tape from 2011 to 2019, and a historical control group (CG) of 81 patients was treated with a noncoated tape and underwent incontinence surgery from 1999 to 2009. We compared patient-reported outcome measures (PROMs) with the incontinence outcome questionnaire (IOQ)., Results: The median follow-up was 2½ years in both groups. Based on responses to the IOQ, a statistically significantly shorter time of recovery (IOQ 15: 21.3 ± 26.4 [TG], 40.2 ± 38.5 [CG], p = 0.02), improvement of sex life (IOQ 13: 34.1 ± 29.4 [TG] vs. 65.3 ± 35.6 [CG], p = 0.01) and less voiding dysfunction (IOQ 19: 30.9 ± 28.1 [CG], 9.3 ± 18.6 [TG], p = 0.01) were observed in the TG. Objectively, no postoperative urinary retention was observed in the TG, but four cases were described in the CG. Ten patients needed a reoperation for SUI in the CG compared to three in the TG (p = 0.03)., Conclusion: The titanium-covered transobturator sling had superior recovery time, improved sexual function and reduced reoperation rate compared to a historical polypropylene group., (© 2021. The Author(s).)

Inappropriate activation of TLR7 and TLR8 is linked to several autoimmune diseases, such as lupus erythematosus. Here we report on the efficient structure-based optimization of the inhibition of TLR8, starting from a co-crystal structure of a small screening hit. Further optimization of the physicochemical properties for cellular potency and expansion of the structure-activity relationship for dual potency finally resulted in a highly potent TLR7/8 antagonist with demonstrated in vivo efficacy after oral dosing., Competing Interests: The authors declare no competing financial interest., (© 2022 American Chemical Society.)

Background: Significant risk of bias and limitations in outcome selections in trials evaluating conservative treatments for the management of Pelvic Organ Prolapse (POP) have been highlighted and preclude comparability of outcomes, synthesis of primary studies and high quality evidence., Objectives: As systematic review of the reported outcomes is the first step in the process of development of a Core Outcome Set (COS), we aimed to systematically review reporting of outcomes and outcome measures in Randomised Control Trials (RCTs) on conservative treatments for POP and develop an inventory of them for consideration as core outcome and outcome measures sets. We evaluated methodological quality, outcome reporting quality and publication characteristics and their associations among published RCTs., Study Design: Systematic review of RCTs identified from the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and MEDLINE (Pubmed). RCTs evaluating the effectiveness of conservative interventions for the management of POP were considered for inclusion. Outcomes and outcome measures were obtained from the RCTs and an inventory was created. Outcomes were grouped in domains and themes. Methodological quality, outcome reporting quality and publication characteristics were evaluated and statistically analysed., Results: Twenty-five trials (3179 women) were included and reported 31 outcomes and 50 outcome measures. Reporting rates of the outcomes investigated ranged between 4% and 56%. The most commonly reported outcome domains were patient reported symptoms, stage of POP expressed as POP-Q stage, and quality of life. Univariate analysis demonstrated no significant correlations of methodological and outcome reporting parameters., Conclusions: There is a need to increase comparability of RCTs. Reporting standardized outcomes included in a COS for conservative interventions for POP will facilitate the comparability across RCTs. While the process of developing COS is in progress, we propose the interim use of the three most commonly reported outcomes in each domain: patient-reported outcomes (symptom distress including bowel and urinary symptoms, sexual function), stage of prolapse and quality of life parameters using validated questionnaires (Pelvic Floor Distress Inventory 20 (PFDI-20), Pelvic Floor Impact Questionnaire/Health related quality of life (PFIQ-7/HRQOL) and Pelvic Organ Prolapse Impact Questionnaire (POPIQ-7)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)