A physiologically relevant, estradiol-17ß [E2]-responsive in vitro tissue-engineered model of the vaginal epithelium for vaginal tissue research.

AIMS: There are many situations where preclinical models of the human vagina would be valuable for in vitro studies into the pathophysiology of vaginally transmitted diseases, microbicide efficacy, irritability testing, and particularly, for assessing materials to be inserted in the vagina for support of the pelvic floor. The aim of this study is to develop a physiologically relevant, low cost, and ethically suitable model of the vagina using sheep vaginal tissue (SVT) to reduce the need for animal testing in gynecological research. METHODS: Tissue-engineered (TE) vaginal models were developed by culturing primary vaginal epithelial cells and vaginal fibroblasts, isolated from the native SVTs on decellularized sheep vaginal matrices at an air-liquid interface. Morphological analyses of the models were conducted by performing hematoxylin and eosin staining and further characterization was done by immunohistofluorescence (IHF) of structural proteins and cytokeratins. RESULTS: Histological analysis of the models revealed a gradual formation of a stratified epithelium on our decellularized matrices and cell metabolic activity remained high for 21 days as measured by the resazurin assay. Our models showed a dose-dependent response to estradiol-17ß [E2 ] with an increase in the vaginal epithelium thickness and cellular proliferation under higher E2 concentrations (100-400 pg/ml). The physiological relevance of these results was confirmed by the IHF analysis of Ki67, and cytokeratins 10 and 19 expression. CONCLUSION: In this study, we have developed an estradiol-responsive TE vaginal model that closely mimics the structural and physiological properties of the native SVT.

Complications related to use of mesh implants in surgical treatment of stress urinary incontinence and pelvic organ prolapse: infection or inflammation?

The surgical mesh material used in the surgical treatment of stress urinary incontinence (SUI) and pelvic organ prolapse (POP) in women is associated with significant complications in some women. This has recently become a public health issue with involvement of national parliaments and regulatory bodies. The occurrence of mesh complications is thought to be a result of multifactorial processes involving problems related to the material design, the surgical techniques used and disease, and patient-related factors. However, the infectious complications and mesh-tissue interactions are least studied. The aim of this article is to review any previous clinical and basic scientific evidence about the contribution of infectious and inflammatory processes to the occurrence of mesh-related complications in SUI and POP. A literature search for the relevant publications without any time limits was performed on the Medline database. There is evidence to show that vaginal meshes are associated with an unfavourable host response at the site of implantation. The underlying mechanisms leading to this type of host response is not completely clear. Mesh contamination with vaginal flora during surgical implantation can be a factor modifying the host response if there is a subclinical infection that can trigger a sustained inflammation. More basic science research is required to identify the biological mechanisms causing a sustained inflammation at the mesh-tissue interface that can then lead to contraction, mesh erosion, and pain.

The changing regulatory landscape for biomedical implants and its relationship to withdrawal of some vaginal mesh products.

PURPOSE OF REVIEW: Advancements in biomedical engineering and advanced therapies including tissue engineering products necessitate revisions to the regulation and governance of their production and use to ensure patient safety. In this review, the current regulations and recent improvements on the governance of biomedical devices are reviewed. RECENT FINDINGS: Current regulations on approval of biomedical devices failed to address some important aspects related to the definition of biocompatibility of medical implants. The main issue was that the failure to establish design requirements for a specific application - in this case, the pelvic floor. Another issue was the lack of knowledge on disease mechanisms leading to an inability to define clear targets for surgical treatment. A clear example of this is the recent vaginal mesh scandal. SUMMARY: Surgical innovations are inherently challenging. It is no surprise that the regulatory landscape lags behind advancements in biomedical technologies. Very recent modifications to the available regulations particularly in Europe aim to establish a robust, transparent, predictable and sustainable regulatory framework for medical devices, which ensures patient safety while supporting innovation.

Improving the biocompatibility of biomaterial constructs and constructs delivering cells for the pelvic floor.

PURPOSE OF REVIEW: Interactions between biomaterials and biomaterial-delivering cells and the host tissues are complexly affected by the material itself, the ultrastructure of the overall construct and cells and other bioactive factors involved. The aim of this review is to review the current understanding on the definitions of biocompatibility and current advances in improving biocompatability of tissue-engineered constructs. RECENT FINDINGS: Some synthetic materials are associated with more foreign body reactions compared with natural materials; however, they allow fabrication of materials with a great diversity of physical and mechanical properties. Material design strategies can be tailored to mimic the natural extracellular matrix topography. There are also advancements in the pharmacological functionalization of materials with improved angiogenic potential that can lead to better tissue response. Stem cells are also used to improve the tissue response of tissue-engineered materials; however, the recent regulations on regenerative medicine products necessitate significant regulatory approval processes for these. SUMMARY: The biggest challenge faced in translation of tissue-engineered constructs into clinical practice relates to their engraftment and poor tissue integration into the challenging wound bed of the pelvic floor. Biocompatibility of tissue engineered constructs can theoretically be improved by the incorporation of bioactive agents, such as vitamins C or oestradiol.

Designing new synthetic materials for use in the pelvic floor: what is the problem with the existing polypropylene materials?

PURPOSE OF REVIEW: This review identifies the clinical complications associated with the design of the current polyproplylene mesh materials used for the treatment of stress urinary incontinence and pelvic organ prolapse. Following on from this, new alternative materials under development for pelvic floor repair are reviewed. RECENT FINDINGS: It is well accepted that the textile properties of the current polypropylene surgical meshes are not suitable for the pelvic floor environment. This together with the chemical nature of the current mesh leads to complications whenever implanted in the pelvic floor of women. New alternative materials for the repair of the pelvic floor have been developed with properties designed to be more appropriate for the biomechanical requirements and implantation requirements for the pelvic floor to reduce these clinical complications. To support this, these newer materials are being rigorously tested using more appropriate in-vitro regimes and animal models. SUMMARY: This chapter summarizes developments in the design of new materials for pelvic floor repair. These are being subjected to preclinical testing to exclude materials, which might fail to work in this dynamic environment by either showing a poor mechanical match to the requirements of the tissue or by provoking sustained inflammation. The hope is that new materials will prove effective without causing the high incidence of unacceptable side-effects currently seen with polypropylene mesh implants.

Tissue engineering for the pelvic floor.

PURPOSE OF REVIEW: To set in context the challenge of developing tissue-engineered constructs for use in the female pelvic floor compared with at least 30 years of research progress in tissue engineering for other tissues. RECENT FINDINGS: The relative lack of information on the mechanical requirements of the pelvic floor in women who have suffered damage to these tissues is a major challenge to designing tissue-engineered materials for use in this area. A few groups are now using autologous cells and biomaterials to develop constructs for repair and regeneration of the pelvic floor. Progress with these has reached early stage evaluation in small animal models. Meanwhile the regulatory challenge of introducing laboratory-expanded cell therapy into the clinic is prompting groups to look at alternatives, such as using lipoaspirate retrieved in theatre as a source of adult stem cells for a number of tissues. In our group, we have begun to look at lipoaspirate for repair of the pelvic floor. SUMMARY: There is a need for research to harvest the advances made over the last 30 years in developing tissue-engineered constructs for several tissues to now tackle the problems of the weakened pelvic floor. At present, there are relatively few groups engaged in this challenge despite the growing clinical need.

Current state of urethral tissue engineering.

PURPOSE OF REVIEW: Urethrotomy remains the first-line therapy in the treatment of a urethral stricture despite data showing no real chance of a cure after repeated urethroplasties. An anastomotic or an augmentation urethroplasty with oral mucosa should be offered to patients with a failed urethrotomy. The availability of grafts can be a concern for both patients and surgeons. The potential for a tissue-engineered solution has been explored in recent years and is explored in this article. RECENT FINDINGS: More than 80 preclinical studies have investigated a tissue-engineered approach for urethral reconstruction mostly using decellularized natural scaffolds with or without cell seeding. The animal models used in preclinical testing are not representative of disease processes seen with strictures in man. The available clinical studies were of small sample size and lacked control groups. The choice of biomaterial were mostly acellular matrices derived from natural extracellular matrix. The reported success rates in the pilot clinical studies were highly variable. SUMMARY: The research with tissue engineering of the urethra has not yet been translated into a clinically available material. This is an area where much more research is needed and we would conclude that it is an area of unmet clinical need where users of tissue-engineered urethra in the future need to carry out a rigorous basic science programme and need to be cautious in drawing conclusions based on initial experience and report on long-term clinical results.

An estradiol releasing, proangiogenic hydrogel as a candidate material for use in soft tissue interposition.

INTRODUCTION AND OBJECTIVES: Soft tissue interposition (STI) using local and/or regional flaps is often necessary in urogenital reconstruction to stimulate wound healing and prevent recurrence. Harvesting STI flaps can cause donor site morbidity and may not be available in some patients. In this study, we designed estradiol (E2) releasing hydrogel that could be used as an alternative to a STI flap and to investigate its ability to stimulate tissue production and angiogenesis. MATERIALS AND METHODS: A hydrogel was constructed by crosslinking a solution of estradiol, methacrylated gelatin (15%, w/v), and methacrylated hyaluronic acid (1%, w/v). The release of estradiol was measured using a UV-spectrophotometer (λmax = 220 nm). Angiogenesis was evaluated by an ex ovo chicken embryo chorioallantoic membrane (CAM) assay. RESULTS: Estradiol was gradually released from the hydrogel over 21 days. The hydrogels could be easily manipulated with surgical forceps without any deformation. The hydrogels significantly increased collagen production of human dermal fibroblasts (HDFs). Scanning electron microscopic examination demonstrated that HDFs produced significantly more extracellular matrix (ECM) on estradiol releasing hydrogels compared with the controls. Estradiol releasing hydrogels doubled the number of blood vessels growing toward the hydrogel compared with the controls (vasculogenic index, 59.6 [±6.4] and 25.6 [±4.0], respectively; [P < 0.05]). CONCLUSION: We present a proangiogenic, degradable hydrogel that can be used as an off-the-shelf available substitute to traditional STI flaps. This is achieved by using estradiol as a potent stimulator of new tissue production and new blood vessel formation.

Use of a simple in vitro fatigue test to assess materials used in the surgical treatment of stress urinary incontinence and pelvic organ prolapse.

AIMS: Stress urinary incontinence and pelvic organ prolapse are very common conditions with a proportion of patients requiring implantation of synthetic materials for a durable repair. However increasing numbers of post-surgical complications have been reported related to the use of polypropylene meshes. One hypothesis for the adverse response is poor mechanical matching of the relatively stiff polypropylene mesh particularly as materials in the pelvic floor will need to cope with decades of distension as occurs with increase of intraabdominal pressure on coughing, laughing, or sneezing. METHODS: In this study we have undertaken a very simple fatigue testing regime to compare the mechanical abilities of six materials. Four commercial meshes in clinical use and two novel electrospun materials not yet evaluated in the clinic were assessed using a uniaxial tensile test. This was performed on six samples of each dry material and on another six samples of each material after just 3 days of fatigue conditions using a dynamic bioreactor. RESULTS: The four commercial materials showed permanent mechanical deformation after just 3 days of stretching these materials by 25% elongation on a regular dynamic cycle, whereas the two new materials presented more elastic properties without deformation. CONCLUSIONS: We suggest that a test as simple as this 3-day fatigue testing is sufficient to distinguish between materials which have already been found to cause complications clinically and newer materials yet to be tested clinically which will hopefully prove more mechanically appropriate for implantation in the pelvic floor.

The clinical role of LASER for vulvar and vaginal treatments in gynecology and female urology: An ICS/ISSVD best practice consensus document.

BACKGROUND: The clinical role of LASER for vulvar and vaginal treatments in gynecology and female urology is controversial. AIMS: In this best practice document, we propose recommendations for the use of LASER for gynecologic and urologic conditions such as vulvovaginal atrophy, urinary incontinence, vulvodynia, and lichen sclerosus based on a thorough literature review. MATERIALS & METHODS: This project was developed between January and September 2018. The development of this document followed the ICS White Paper Standard Operating Procedures. RESULTS: Most of the available studies are limited by their design; for example they lack a control group, patients are not randomized, follow up is short term, series are small, LASER is not compared with standard treatments, and studies are industry sponsored. Due to these limitations, the level of evidence for the use of LASER in the treatment of these conditions remains low and does not allow for definitive recommendations for its use in routine clinical practice. Histological evidence is commonly reported as proof of tissue regeneration following LASER treatment. However, the histological changes noted can also be consistent with reparative changes after a thermal injury rather than necessarily representing regeneration or restoration of function. The use of LASER in women with vulvodynia or lichen sclerosus should not be recommended in routine clinical practice. There is no biological plausibility or safety data on its use on this population of women. DISCUSSION: The available clinical studies do not present convincing data regarding the efficacy of LASER for the treatment of vaginal atrophy or urinary incontinence. Also, while short-term complications seem to be uncommon, data concerning long-term outcomes are lacking. CONCLUSION: At this point, LASER is not recommended for routine treatment of the aforementioned conditions unless part of well-designed clinical trials or with special arrangements for clinical governance, consent, and audit.

The Clinical Role of LASER for Vulvar and Vaginal Treatments in Gynecology and Female Urology: An ICS/ISSVD Best Practice Consensus Document.

In this best practice document, we propose recommendations for the use of LASER for gynecologic and urologic conditions such as vulvovaginal atrophy, urinary incontinence, vulvodynia, and lichen sclerosus based on a thorough literature review. Most of the available studies are limited by their design; for example, they lack a control group, patients are not randomized, follow-up is short term, series are small, LASER is not compared with standard treatments, and most studies are industry sponsored. Because of these limitations, the level of evidence for the use of LASER in the treatment of these conditions remains low and does not allow for definitive recommendations for its use in routine clinical practice. Histological evidence is commonly reported as proof of tissue regeneration after LASER treatment. However, the histological changes noted can also be consistent with reparative changes after a thermal injury rather than necessarily representing regeneration or restoration of function. The use of LASER in women with vulvodynia or lichen sclerosus should not be recommended in routine clinical practice. There is no biological plausibility or safety data on its use on this population of women. The available clinical studies do not present convincing data regarding the efficacy of LASER for the treatment of vaginal atrophy or urinary incontinence. Also, although short-term complications seem to be uncommon, data concerning long-term outcomes are lacking. Therefore, at this point, LASER is not recommended for routine treatment of the aforementioned conditions unless part of well-designed clinical trials or with special arrangements for clinical governance, consent, and audit.

Demonstration of improved tissue integration and angiogenesis with an elastic, estradiol releasing polyurethane material designed for use in pelvic floor repair.

AIMS: Pelvic organ prolapse and stress urinary incontinence affect 40-50% of postmenopausal women worldwide. Polypropylene meshes have been extensively used for the surgical intervention of these disorders; however, these meshes can lead to severe complications in some patients. The need for synthetic materials more suited for use in pelvic floor repair is widely accepted. This study aims to develop an electrospun 17-ß-estradiol releasing polyurethane (PU) scaffold that not only provides the appropriate mechanical support but can also stimulate new extracellular matrix (ECM) production and angiogenesis. METHODS: PU scaffolds with and without 17-ß-estradiol (25 and 50 mg/g) were prepared by blend electrospinning. Mechanical properties of scaffolds were assessed by uniaxial cyclic and non-cyclic testing. The viability and ECM production of human adipose derived mesenchymal stem cells (hADMSCs) cultured on 17-ß-estradiol releasing PU scaffolds was evaluated. Angiogenic potential of estradiol releasing scaffolds was demonstrated by using an ex ovo chick chorioallantoic membrane (CAM) assay. RESULTS: The inclusion of estradiol in PU scaffolds did not change the ultrastructure but it significantly increased the ultimate tensile strength of scaffolds. hADMSCs on estradiol-releasing PU scaffolds showed more ECM production. The CAM assay revealed a significantly higher angiogenic potential of estradiol-releasing PU scaffolds with an additive effect seen when hADMSCs cultured on estradiol scaffolds. Histological examination of CAM tissue sections showed extensive cellular infiltration and a good tissue integration for all constructed scaffolds. CONCLUSIONS: This study shows the angiogenic potential of estradiol-releasing PU scaffolds with appropriate strength and elasticity desirable to support the pelvic floor.

Turkish version of the Ureteral Stent Symptoms Questionnaire: linguistic and psychometric validation.

PURPOSE: Ureteric stents are frequently used in urology practice and can cause significant impairment in quality of life (QoL). The aim of this study was to validate the Ureteral Stent Symptoms Questionnaire (USSQ) to be used in the evaluation of stent-related symptoms and impairment in QoL in Turkish-speaking patients. METHODS: After linguistic validation of the original USSQ into Turkish language, the Turkish version of the USSQ (T-USSQ) was self-administered to all participants at week 1 and 4 after stent placement for test-retest reliability and internal consistency and at week 8 (4 weeks after stent removal) for sensitivity to change analysis. Control patients completed the form only once. Additionally male and female patients completed the validated Turkish versions of International Prostate Symptom Score (IPSS) and Marmara Overactive Bladder (mOAB) Symptom Scores, respectively. RESULTS: A total of 68 patients with ureteral stents and 37 controls were available for the final analysis. The Cronbach's alpha value was higher than 0.7 at week 1 for all sub-domains except additional problems domain. The test-retest reliability of the T-USSQ was high for all sub-domains except the additional problems domain. Relatively high correlation coefficients were found for the visual analog scale for pain, IPSS (for males), mOAB score (for females) with the corresponding USSQ domains, suggesting good convergent validity. Also the T-USSQ could effectively differentiate between patients and controls. CONCLUSIONS: The T-USSQ is a reliable and robust instrument that can be self-administered to patients of Turkish population with ureteral stent in the clinical applications.

Stem cell therapies in post-prostatectomy erectile dysfunction: a critical review.

INTRODUCTION: Erectile dysfunction (ED) is still a common complication of radical prostatectomy. Current treatments of ED are mainly symptomatic. Mesenchymal stem cells (MSCs) have been widely investigated as a potential curative treatment. Although MSC therapy consistently improved erectile functions in the pre-clinical studies the initial expectations seem to be unmet. The aim of this study is to critically review the existing studies on use of stem cells in post-prostatectomy ED and understand factors that preclude clinical translation of the available evidence. MATERIALS AND METHODS: A literature search for all pre-clinical and clinical studies investigating MSCs in the treatment of post-prostatectomy ED published between January 2009 and March 2016 was performed using the PubMed database. RESULTS: A total of 24 pre-clinical studies investigated MSC based treatments in cavernous nerve injury (CNI) rodent models. In the majority of these studies intracavernous injection of MSCs at the time injury improved erectile functions. There is less data on the efficacy of MSCs when applied in a chronic disease state. Allogeneic or xenogeneic MSCs were similarly effective with limited data on immunologic response. There is a lack of conclusive data on in vivo fate of MSCs and the best route of MSC administration. CONCLUSION: MSC therapy consistently improved erectile functions after CNI. There seems to be a consensus on the disease model used and outcome evaluation however further studies focusing on immunologic response to MSCs, their mechanism of action and in vivo fate are needed before their widespread use in clinic.

Safety and efficacy of retropubic or transobturator midurethral slings in a randomized cohort of Turkish women.

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of retropubic (RP) or transobturator (TO) midurethral slings (MUS) in a prospective randomized cohort of Turkish women. PATIENTS AND METHODS: A total of 54 women with urodynamic stress urinary incontinence (SUI) were randomized to undergo either RP or TO MUS between August 2006 and February 2013 in a tertiary referral center by a single surgeon. All patients had history, physical examination, urodynamic evaluation and quality of life assessments. The validated Turkish versions of the SEAPI, ICIQ-SF and OAB-V8 questionnaires were used. The Advantage® RP and the Obtryx® TO MUS Systems were used for all RP and TO procedures. RESULTS: Twenty-seven patients were randomized to each group. The median follow-up was 48.5 ± 21.8 months. The median hospital stay was 24.0 ± 4.8 h and median operative time was 35.0 ± 19.9 min. The overall objective and subjective cure rates were 92.6 and 79.6%, respectively. The quality of life of all patients significantly increased after the operation compared to their preoperative status. Patients with a poorer subjective cure rate were those with mixed urinary incontinence, whose preoperative SEAPI and OAB-V8 scores were significantly higher. CONCLUSION: MUS surgery is highly effective and could safely be performed in a cohort of Turkish women with SUI in subspecialty centers by experienced surgeons. There is no significant difference between RP or TO applications in terms of safety and efficacy. Further studies with long-term follow-up data are required.

Mesenchymal stem cell therapy in treatment of erectile dysfunction: autologous or allogeneic cell sources?

OBJECTIVE: To compare the efficacy of intracavernosal injection of autologous and allogeneic mesenchymal stem cells as potential treatment of erectile dysfunction in an experimental rat model. METHODS: Mesenchymal stem cells were isolated from rat paratesticular fat tissue. Bilateral cavernous nerve injury was carried out followed by immediate intracavernosal injection of either autologous or allogeneic mesenchymal stem cells or mesenchymal stem cell lysates. One month after injection, erectile function was evaluated by means of intracavernosal pressure measurement. All rats were eventually killed, and penile tissues were taken for immunhistochemical and molecular investigation. RESULTS: A total of 36 Sprague-Dawley rats were used. The mean maximum intracavernosal pressure in the sham-operated, autologous and allogeneic mesenchymal stem cell injection groups were significantly better compared with the vehicle injection group (80.5 [3.56], 71.1 [2.9] and 69.2 [3.2] vs 40.33 [4.4], respectively). Mean maximum intracavernosal pressure to mean arterial pressure ratios in the autologous and allogeneic mesenchymal stem cell and mesenchymal stem cell lysate injection groups were not significantly different. CONCLUSIONS: Intracavernosal injection of both autologous or allogeneic mesenchymal stem cells improve erectile functions in a rat model of cavernous nerve injury. Allogeneic mesenchymal stem cells might provide clinicians with ready to use, standardized and, in certain cases, more effective products. More studies focusing on long-term immunological aspects of allogeneic mesenchymal stem cells are required.

A scoping review of tissue interposition flaps used in vesicovaginal fistulae repair.

Background: Research on the use of tissue interposition flaps (TIFs) in vesicovaginal fistulae (VVF) repair is a broad area where a very wide range of natural and synthetic materials have been used. The occurrence of VVF is also diverse in the social and clinical settings, resulting in a parallel heterogeneity in the published literature on its treatment. The use of synthetic and autologous TIFs in VVF repair is not yet standardized with a lack of the most efficacious type and technique of the TIF. Objectives: The aim of this study was to systematically review all synthetic and autologous TIFs used in the surgical repair of VVFs. Data sources and methods: In this scoping review, the surgical outcomes of autologous and synthetic interposition flaps used in VVF treatment meeting the inclusion criteria were determined. We searched the literature using Ovid MEDLINE and PubMed databases between 1974 and 2022. Study characteristics were recorded, and data on the change in fistulae size and location, surgical approach, success rate, preoperative patient evaluation and outcome evaluation were extracted from each study independently by two authors. Results: A total of 25 articles that met the inclusion criteria were included in the final analysis. A total of 943 and 127 patients who had received autologous and synthetic flaps, respectively, were included in this scoping review. The fistulae characteristics were highly variable with regard to their size, complexity, aetiology, location and radiation. Outcome assessments of fistulae repair in included studies were mostly based on symptom evaluation. Physical examination, cystogram and methylene blue test were the methods in order of preference. Postoperative complications, such as infection, bleeding, donor site, pain, voiding dysfunction and other complications, were reported in patients after fistulae repair in all included studies. Conclusion: The use of TIFs in VVF repair was common especially in complex and large fistulae. Autologous TIFs appear to be the standard of care at the moment, and synthetic TIFs were investigated in prospective clinical trials in a limited number of selected cases. Evidence levels of clinical studies evaluating the effectiveness of interposition flaps were overall low.

The relationship between urinary incontinence and abdominal muscle thickness in community-dwelling older women undergoing comprehensive geriatric assessment.

PURPOSE: Urinary incontinence (UI) is one of the most common geriatric syndromes in older adults, especially in women. The aim of this study is to show the relationship between urinary incontinence and abdominal muscle thickness measured by muscle ultrasonography (US) in community-dwelling older women adults. METHODS: Eighty-seven community-dwelling older women participated in our study. The presence and the type of UI were recorded. Clinical and demographic characteristics were collected, and a comprehensive geriatric assessment was performed on all participants. Abdominal muscle layer thicknesses were evaluated with muscle US. RESULTS: The prevalence of UI was 55.2% (n = 48) of the study population. The median [IQR] age of the patients in the UI group was 73.0 [69.0-77.5] years and it was 69.0 [67.0-73.0] years in patients without UI (p = 0.007). Abdominal muscle thicknesses were measured smaller in patients with UI than those without UI except for internal oblique muscle thickness. The median [IQR] rectus abdominis muscle thickness was lower in patients with UI than in patients without UI, and the difference was statistically significant (p < 0.003). RA muscle was associated with UI regardless of age, polypharmacy, malnutrition, and frailty (OR: 0.58; 95% CI 0.38-0.89; p = 0.01). CONCLUSIONS: We have shown that UI was independently related to the rectus abdominis muscle thickness, which may reflect the function and mass of the pelvic floor muscles.

Defining Molecular Treatment Targets for Bladder Pain Syndrome/Interstitial Cystitis: Uncovering Adhesion Molecules.

Bladder pain syndrome/interstitial cystitis (BPS/IC) is a debilitating pain syndrome of unknown etiology that predominantly affects females. Clinically, BPS/IC presents in a wide spectrum where all patients report severe bladder pain together with one or more urinary tract symptoms. On bladder examination, some have normal-appearing bladders on cystoscopy, whereas others may have severely inflamed bladder walls with easily bleeding areas (glomerulations) and ulcerations (Hunner's lesion). Thus, the reported prevalence of BPS/IC is also highly variable, between 0.06% and 30%. Nevertheless, it is rightly defined as a rare disease (ORPHA:37202). The aetiopathogenesis of BPS/IC remains largely unknown. Current treatment is mainly symptomatic and palliative, which certainly adds to the suffering of patients. BPS/IC is known to have a genetic component. However, the genes responsible are not defined yet. In addition to traditional genetic approaches, novel research methodologies involving bioinformatics are evaluated to elucidate the genetic basis of BPS/IC. This article aims to review the current evidence on the genetic basis of BPS/IC to determine the most promising targets for possible novel treatments.