PEOPLE: Lifestyle and comorbidities as risk factors for pelvic organ prolapse-a systematic review and meta-analysis PEOPLE: PElvic Organ Prolapse Lifestyle comorbiditiEs.

INTRODUCTION AND HYPOTHESIS: The literature is scarce regarding the effects of comorbidities, clinical parameters, and lifestyle as risk factors for pelvic organ prolapse (POP). This study was performed to systematically review the literature related to body mass index (BMI), waist circumference, diabetes mellitus (DM), hypertension (HT), dyslipidemia, chronic constipation, smoking, chronic cough, occupation, and striae and varicose veins as determinants for POP. METHODS: Search terms in accordance with Medical Subject Headings were used in PubMed, Embase, LILACS, and the Cochrane Library. Clinical comparative studies between women with and without POP and containing demographic and/or clinical raw data related to lifestyle and/or comorbidities were included. The ROBINS-I (risk of bias in non-randomized studies of interventions) instrument was used. Fixed-effects and random-effects models were used for homogeneous and heterogeneous studies, respectively. RESULTS: Forty-three studies were included in the meta-analysis. BMI < 25 kg/m2 was found to be a protective factor for POP [OR 0.71 (0.51, 0.99); p = 0.04], and BMI > 30 kg/m2 was a risk factor for POP [OR 1.44 (1.37, 1.52); p < 0.00001]. Waist circumference (≥ 88 cm) was reported as a risk factor for POP [OR 1.80 (1.37, 2.38); p < 0.00001], along with HT [OR 1.18 (1.09, 1.27); p = 0.04], constipation [OR 1.77 (1.23, 2.54); p < 0.00001], occupation [OR 1.86 (1.21, 2.86); p < 0.00001], persistent cough [OR 1.52 (1.18, 1.94); p < 0.0001]), and varicose veins [OR 2.01 (1.50, 2.70); p = 0.12]. CONCLUSIONS: BMI < 25 kg/m2 is protective while BMI > 30 kg/m2 is a risk factor for POP. Large waist circumference, dyslipidemia, HT, constipation, occupation, persistent cough, and varicose veins are also determinants for POP.

Preclinical Evaluation of the Tumorigenic and Immunomodulatory Properties of Human Bone Marrow Mesenchymal Stromal Cell Populations with Clonal Trisomy 5.

Cytogenetic aberrations may emerge in human mesenchymal stromal cells (MSC) during ex vivo expansion for cell therapy. We have detected clonal trisomy 5 in two distinct autologous MSC products expanded from bone marrow which, based on the current quality control criteria, could not be released for clinical use. Although a safety concern, it is still unclear to what extent recurrent aneuploidies detected in MSC products may affect the threshold for neoplastic transformation or the medicinal properties of these cells. We have carried out an exploratory preclinical study to evaluate these MSC products with clonal trisomy 5, regarding their oncogenic and immunomodulatory potential. Cell population growth in vitro was reduced in MSC cultures with clonal trisomy 5 compared with the population growth of their euploid MSC counterparts, based on a lower cumulative population doubling level, reduced cell proliferation index, and increased senescence-associated beta-galactosidase activity. Subcutaneous injection of clinically relevant amount of MSC population, either with or without clonal trisomy 5, did not generate tumors in immunodeficient mice within a follow-up period of six months. Most importantly, MSC population with clonal trisomy 5 kept immunomodulatory properties upon interferon gamma (IFNγ) licensing, displaying overexpression of IDO, CXCL9, CXCL10, and CXCL11, in a similar fashion than that of IFNγ-licensed euploid MSC. Our findings suggest that bone marrow MSC products with clonal trisomy 5 may retain their therapeutic potential, based on poor tumor initiating capability and preserved immunomodulatory potency. This preclinical evidence may further support the definition of release criteria of autologous MSC products for cell therapy under critical clinical scenarios. This trial is registered with Clinical Study registration number: RBR-29x2pr.

Senescence State in Mesenchymal Stem Cells at Low Passages: Implications in Clinical Use.

Mesenchymal stem cells (MSCs) are multipotent cells found in various tissues and are easily cultivated. For use in clinical protocols, MSCs must be expanded to obtain an adequate number of cells, but a senescence state may be instituted after some passages, reducing their replicative potential. In this study, we report a case where MSC derived from an elderly donor acquired a senescence state after three passages. The bone marrow was aspirated from a female patient submitted to a cell therapy for the incontinency urinary protocol; MSCs were cultivated with DMEM low glucose, supplemented with 10% autologous serum (AS) plus 1% L-glutamine and 1% antibiotic/antimycotic. Senescence analysis was performed by ß-galactosidase staining after 24 and 48 h. Controls were established using BM-MSC from healthy donors and used for senescence and gene expression assays. Gene expression was performed using RT-PCR for pluripotency genes, such as SOX2, POU5F1, NANOG, and KLF4. MSC telomere length was measured by the Southern blotting technique, and MSCs were also analyzed for their capacity to differentiate into adipocytes, chondrocytes, and osteocytes. The patient's MSC expansion using AS displayed an early senescence state. In order to understand the role of AS in senescence, MSCs were then submitted to two different culture conditions: 1) with AS or 2) with FBS supplementation. Senescence state was assessed after 24 h, and no statistical differences were observed between the two conditions. However, patients' cells cultured with AS displayed a higher number of senescence cells than FBS medium after 48 h (p = 0.0018). Gene expression was performed in both conditions; increased expression of KLF4 was observed in the patient's cells in comparison to healthy controls (p = 0.0016); reduced gene expression was observed for NANOG (p = 0.0016) and SOX2 (p = 0.0014) genes. Telomere length of the patient's cells was shorter than that of a healthy donor and that of a patient of similar age. Osteocyte differentiation seemed to be more diffuse than that of the healthy donor and that of the patient of similar age. MSCs could enter a senescence state during expansion in early passages and can impact MSC quality for clinical applications, reducing their efficacy when administered.

Predictors for long-term adherence to vaginal pessary in pelvic organ prolapse: a prospective study.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate the rate of adherence to pessary treatment for pelvic organ prolapse (POP), to identify factors associated with long-term (longer than 1 year) use of vaginal pessaries in Brazilian women with POP and its impact on quality of life (QoL). METHODS: A prospective observational study assessed 247 consecutive women candidates for a pessary to manage symptomatic POP. Patients were fitted with a ring pessary and follow-up visits were performed at 1, 6, and 12 months. Pessary complications and reasons for discontinuation were recorded. Prolapse Quality of Life Questionnaire (P-QoL) was applied at baseline and after 1 year of treatment. We used a logistic regression model for the analyses, with p < 0.05 for significance. RESULTS: A total of 236 women were included in the study, of whom 110 (46.6%) maintained the pessary treatment for longer than 12 months. The main reason for pessary discontinuation was the patient opting for surgery (50.8%). Vulvovaginitis was the main long-term complication (44.5%), followed by vaginal ulceration (16.4%) and urinary urgency (10%). No prior hysterectomy (OR = 2.26; 95% CI 1.19-4.31), vaginal estrogen use (OR = 1.94; 95% CI 1.06-3.52), and mean age (OR = 1.03; 95% CI 1.01-1.06) were variables associated with long-term use of vaginal pessary (p < 0.05 for all). Total P-QoL score significantly changed with pessary use (519.1 at baseline and 260 after 12-month treatment, p < 0.00). CONCLUSIONS: Our study suggests that no prior hysterectomy, the local estrogen therapy, and age might be factors associated with use of a ring vaginal pessary for longer than 1 year. Long-term pessary users had a significant improvement in their quality of life.

Is there a correlation between a 20-min pad-test and subjective urine leakage amount?

INTRODUCTION AND HYPOTHESIS: The quantification of urinary incontinence (UI) is widely used in clinical practice to guide the prognosis and treatment, and the pad test is an inexpensive, quick, and easy tool to assess UI that has been used in studies in the literature. Another way to evaluate UI is the subjective urine leakage amount, but no studies have tried to correlate it with the 20-min pad test. Therefore, this study aimed to assess the correlation of the 20-min pad test with the subjective urine leakage amount and compare it with the pelvic floor function. METHODS: This is a cross-sectional study with a sample size of 72 participants. It evaluated pelvic floor muscle strength as well as the duration of symptoms and pad weight. It used mean, standard deviation, median, and 95% confidence interval. In addition, ANOVA, Kruskal-Wallis, and Spearman's correlation coefficient were used. The significance level was fixed at 5% (significant if P < 0.05). RESULTS: Only age was different between leakage volumes; participants who report greater UI volume were older than the participants who leaked less urine. There were no differences related to the duration of symptoms between different UI volumes and pad weights according to the subjective volume reported. Spearman's coefficient between pad weight and subjective volume of urine leakage was rs = 0.558 (P ≤ 0.0001), demonstrating a moderate positive correlation. CONCLUSIONS: There was a moderate correlation between the UI volume reported and the 20-min pad test. Additionally, no differences related to pelvic floor function were detected.

Effects of voluntary pre-contraction of the pelvic floor muscles (the Knack) on female stress urinary incontinence-a study protocol for a RCT.

BACKGROUND: Stress urinary incontinence (SUI) is a subtype of urinary incontinence that occurs more commonly amongst women. The pelvic floor muscle training (PFMT) is considered the gold standard for treating SUI. Another technique called the Knack postulated that pre-contraction of the pelvic floor muscles (PFM) during activities of increasing intra-abdominal pressure prevents urinary loss. Currently, there are no studies supporting the Knack for the treatment of SUI. Thus, the aim of this study is to test the hypothesis that voluntary pre-contraction of PFM can treat SUI. For this purpose, the following parameters will be analysed and compared amongst (1) the Knack, (2) PFMT and (3) the Knack + PFMT groups: urine leakage as assessed by the pad test, urinary symptoms, muscle function, quality of life, subjective cure, adherence to exercises in the outpatient setting and at home and perceived self-efficacy of PFM exercises. METHODS: A single-centre, double-blind (investigator and outcome assessor) randomised controlled trial with a 3-month follow-up of supervised treatment and an additional 3 months of follow-up (unsupervised) for a total of 6 months of follow-up. Two hundred ten women with mild to moderate SUI will be included, aged between 18 and 70 years. To compare the primary and secondary outcome measures within and between the groups studied (before and after intervention), the ANOVA statistical test will be used. Primary and secondary outcome measures will be presented as mean, standard deviation, 95% confidence interval and median and minimum and maximum values. DISCUSSION/SIGNIFICANCE: This study closes a gap, as voluntary PFM pre-contraction (the Knack) has not yet been included in the physiotherapeutic treatment of SUI, and if shown successful could be implemented in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT03722719 . Registered on October 29, 2018. Study protocol version 1. Was this trial prospectively registered? Yes Funded by: The present study did not receive funding. Anticipated completion date: The anticipated trial commencement and completion dates are October 2018 and October 2021, respectively. Provenance: Not invited. Peer reviewed. Human research ethics approval committee: Research Ethical Board of the Universidade Federal de São Paulo (UNIFESP), Brazil. Human research ethics approval number: 2.517.312.

Telehealth in the rehabilitation of female pelvic floor dysfunction: a systematic literature review.

INTRODUCTION AND HYPOTHESIS: The pandemic caused by coronavirus disease 2019 (COVID-19) increased the awareness and efforts to provide care from distance using information technologies. We reviewed the literature about the practice and effectiveness of the rehabilitation of the female pelvic floor dysfunction via telehealth regarding symptomatology and quality of life and function of pelvic floor muscles (PFM). METHODS: A bibliographic review was carried out in May 2020 in the databases: Embase, Medline/PubMed, LILACS and PEDro. A total of 705 articles were reviewed after the removal of duplicates. The methodological quality of the articles was evaluated by the PEDro scale. Two authors performed data extraction into a standardized spreadsheet. RESULTS: Four studies were included, two being randomized controlled trials. Among the RCTs, only one compared telehealth with face-to-face treatment; the second one compared telehealth with postal treatment. The other two studies are follow-up and cost analysis reports on telehealth versus postal evaluation. Data showed that women who received the intervention remotely presented significant improvement in their symptoms, such as reducing the number of incontinence episodes and voiding frequency, improving PFM strength and improving quality of life compared to women who had the face-to-face treatment. CONCLUSIONS: Telehealth promoted a significant improvement in urinary symptoms, PFM function and quality of life. Telehealth is still emerging, and more studies are needed to draw more conclusions. The recommendations of the governmental authorities, physical therapy councils and corresponding associations of each country also need to be considered.

The role of vaginal palpation in motor learning of the pelvic floor muscles for women with stress urinary incontinence: study protocol for a randomized controlled trial.

BACKGROUND: Approximately 30 to 50% of women are unable to correctly perform pelvic floor muscle (PFM) contractions. For women to benefit from a pelvic floor muscle training (PFMT) programme for stress urinary incontinence (SUI), the awareness phase of PFMT cannot be omitted. The purpose of this study is to evaluate whether vaginal palpation together with verbal instructions about PFMs and body awareness techniques helps women with SUI learn how to correctly contract the PFMs and improve their functions. METHODS: This single-centre, double-blind randomized controlled trial with two intervention groups was designed following the standard protocol items for randomized interventional trials (SPIRIT). The results will be reported in a manner consistent with the Consolidated Standards of Reporting Trials (CONSORT) guidelines. Patients with SUI (n = 172) will be recruited. The experimental group will receive verbal instructions about PFM function and body awareness techniques together with vaginal palpation; the control group will receive similar protocol without vaginal palpation. The primary outcome includes the number of fast-twitch muscle fibres assessed by vaginal palpation and visual observation. Secondary outcomes include power and muscular endurance that will be assessed by visual observation and vaginal palpation (Oxford scale), the use of accessory muscles during the voluntary contraction of PFMs, and the self-efficacy and the expectations for the results using the self-efficacy scale of pelvic floor exercises. DISCUSSION: This study will determine whether vaginal palpation can help women with SUI to correctly perform PFM contractions and improve their functions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03325543 . Registered on 30 November 2017. Study protocol version 1; 30 November 2020. Prospectively registered.

Ability to contract the pelvic floor muscles and association with muscle function in incontinent women.

INTRODUCTION AND HYPOTHESIS: Many women with pelvic floor dysfunction are unable to perform pelvic floor muscle (PFM) contraction. We aimed to assess the ability to contract the PFM and to evaluate the association with muscle function in Brazilian women with urinary incontinence. METHODS: We conducted a retrospective cross-sectional study including incontinent women over the age of 18. The assessment of PFM contraction was carried out by bidigital palpation via the PERFECT scheme. We categorized our population as: group absent: women not able to contract the PFM with verbal instructions; group 1 (1st command): women able to contract their PFM after verbal instructions; group 2 (2nd command): women who needed additional training on PFM anatomy and functioning to contract them. We compared the groups regarding their PFM functionality. We used ANOVA for demographic data and Mann-Whitney test for association analyses and P value < 0.05 for statistical significance. RESULTS: Among 139 women included, 21 (15.1%) were not able to perform the contraction of the PFM. Sixty-five (46.7%) contracted their PFM voluntarily at the first command and 53 (38.1%) at the second command. There was a significant reduction in the PFM function in group 2 in terms of power (p < 0.001), endurance (p < 0.001) and fast contraction (p < 0.001) compared to group 1. CONCLUSION: A high percentage (53.2%) of women were not able to contract their PFM voluntarily without training in PFM anatomy and functioning. Those women had impaired muscle function compared to women able to perform PFM after receiving exclusively oral instructions.

Content and functionality features of voiding diary applications for mobile devices in Brazil: a descriptive analysis.

INTRODUCTION AND HYPOTHESIS: A voiding diary is a method to investigate lower urinary tract symptoms. The purpose was to elaborate a descriptive analysis of nonpaid voiding diaries for mobile applications and to compare them regarding their quality. METHODS: We searched the platforms of iTunes (Apple Inc., Brazil) and Google Play (Google Inc., Brazil) using the keywords: "voiding diary," "bladder diary," "urinary diary," "urinary incontinence," and "pelvic floor." Inclusion criteria were: apps free of charge and specific for voiding diaries in the Portuguese, Spanish, French, or English language. Exclusion criteria were: access or technical problems and pediatric apps. We quantitatively analyzed and compared the apps with each other according to their functionality features and voiding diary topics (type and volume of fluid intake, voiding episodes and volume, type and episodes of incontinence, amount of leakage, urgency, and use of pads and nocturia). We rated the apps using the Mobile App Rating Scale (MARS), whose scores for each feature vary from 1 (worst score) to 5 (best score). RESULTS: Fifty-five apps were eligible; 16 were included for analyses. None presented all 11 topics of the voiding diary, and the median number of available features was 6 (3.75-7). "Incontinence episodes" was present in eight apps, and "nocturia" was present in five. The mean score of apps ranged between 1.7 and 4.5. CONCLUSION: There is variation in the content of voiding topics among the apps. Patients and professionals should choose the app based on the topics of most or particular interest.

Pelvic floor muscle training for female stress urinary incontinence: a randomised control trial comparing home and outpatient training.

INTRODUCTION AND HYPOTHESIS: In the literature, it is suggested that supervised pelvic floor muscle training (PFMT) might be the first option treatment for female stress urinary incontinence (SUI). However, inadequate accessibility to health care and scarce individual resources may prevent adherence to the treatment. Our study is aimed at comparing the efficacy of performing PFMT in an outpatient clinic and at home in Brazilian incontinent women, and to verify if home PFMT may be an alternative to those not able to attend the outpatient sessions. METHODS: A total of 69 women with predominant SUI were randomised into two groups: outpatient PFMT and home PFMT. The primary outcome was the cure of SUI defined as <2 g of leakage in a 20-min pad test. Secondary outcomes were: pelvic floor muscle function; urinary symptoms; quality of life; patient satisfaction; and adherence to home exercise sets. The assessments were conducted at baseline and after 3 months of treatment. Statistical analyses consisted of Student's t, Mann-Whitney U, Chi-squared, and Wilcoxon tests, with a 5% cut-off for significance. RESULTS: A superior objective cure of SUI was observed in the outpatient clinic (62%) compared with the home (28%) PFMT groups (OR: 4.0 [95% CI: 1.4-11.0]; p = 0.011). Secondarily, there was no difference between groups regarding the following: satisfaction with the treatment; quality of life; function of the PFMs; and number of episodes of urine leakage per week. The home adherence to the exercises was superior in the outpatient PFMT group only during the first-month training. CONCLUSIONS: Outpatient PFMT was associated with a higher objective cure of SUI than home PFMT. However, subjective findings show equal benefit of home PFMT providing evidence that this may be an alternative treatment to our population.

Pelvic floor symptoms 5 to 14 years after total versus subtotal hysterectomy for benign conditions: a systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: We aim to compare total versus subtotal abdominal hysterectomy regarding urinary and bowel symptoms and pelvic organ prolapse at long-term follow-up. METHODS: A systematic literature search was performed on the MEDLINE, LILACS, Cochrane CENTRAL and SCOPUS databases and conference abstracts (AAGL, AUGS, ICS) from inception up to November 2017. We included randomized trials comparing total versus subtotal hysterectomy for benign conditions that evaluated pelvic floor symptoms over 5 years of follow-up. Risk of bias and GRADE assessment for quality of evidence were performed. RESULTS: We included four studies involving 566 participants with follow-up ranging from 5 to 14 years. Women who underwent total hysterectomy presented lower risk of reported urinary incontinence [RR 0.74 (CI = 0.58, 0.94) i2 0%; p = 0.02] and stress urinary incontinence [RR 0.84 (CI = 0.71, 0.99) i2 0%; p = 0.04] than those who had subtotal hysterectomy. The events urinary frequency, urge incontinence, incomplete bladder emptying, pelvic organ prolapse, incontinence of stool and constipation did not favor one procedure over another in the long term (P > 0.05). CONCLUSIONS: Patient-reported urinary incontinence and stress urinary incontinence events favored total hysterectomy over subtotal hysterectomy up to 14-year long-term follow-up.

Outpatient biofeedback in addition to home pelvic floor muscle training for stress urinary incontinence: a randomized controlled trial.

AIMS: To test if biofeedback (BF) added to pelvic floor muscle training (PFMT) increases the frequency of home exercises performed by women with stress urinary incontinence (SUI). METHODS: 72 incontinent women were randomized to BF (outpatient BF + home PFMT) or PFMT (outpatient PFMT + home PFMT) groups. ASSESSMENTS: baseline, after 3 months of supervised treatment, at 9-month follow-up (after six additional months of home PFMT only). PRIMARY OUTCOME: frequency of monthly exercises sets performed (exercise diary) after 3-month treatment. SECONDARY OUTCOMES: adherence, urinary symptoms, severity and cure of SUI (pad test <2 g leakage), muscle function, quality of life, and subject cure (satisfaction report with no desire for different treatment) at the two time-points. STATISTICAL ANALYSES: ANOVA and Student's t-test with 5% cut-off for significance. RESULTS: It was observed similar frequency of monthly home exercises sets performed by BF (67.9 out of 82) and PFMT (68.2 out of 82) groups at 3 months. Secondarily, equal satisfaction, but superior objective cure of SUI for BF group after 3-month treatment (P = 0.018; OR: 3.15 [95% CI: 1.20-8.25]). At 9-month follow-up, the adherence to home exercises was similar (around 50%) and significantly dropped in both groups compared to the 3-month results (around 85%). No difference was detected in the objective and subjective cure of SUI between the groups after 9 months. Both therapies similarly improved the muscle function and quality of life during the study (P < 0.005). CONCLUSIONS: Adjunct BF did not increase the frequency of home exercises performed by SUI patients.

Genetics of pelvic organ prolapse: crossing the bridge between bench and bedside in urogynecologic research.

An increasing number of scientists have studied the molecular and biochemical basis of pelvic organ prolapse (POP). The extracellular matrix content of the pelvic floor is the major focus of those investigations and pointed for potential molecular markers of the dysfunction. The identification of women predisposed to develop POP would help in the patients' management and care. This article includes a critical analysis of the literature up to now; discusses implications for future research and the role of the genetics in POP.

Comparação entre as terminologias padronizadas por Baden e Walker e pela ICS para o prolapso pélvico feminino / Comparison between Baden and Walker classification systems and ICS standardization of terminology of female pelvic organ prolapse

OBJETIVO: comparar a classificação de Baden e Walker (BW) para o prolapso pélvico feminino e a preconizada pela Sociedade Internacional de Continência (ICS). MÉTODOS: em trabalho retrospectivo foram analisadas as informações sobre 101 pacientes atendidas no setor de Uroginecologia e Cirurgia Vaginal do Departamento de Ginecologia da UNIFESP/EPM durante investigação uroginecológica. As pacientes foram selecionadas a partir da revisão do prontuário médico, onde foram identificadas aquelas que submeteram-se a exame padronizado pela ICS a fim de quantificar o prolapso pélvico feminino. Conforme preconiza a ICS, o prolapso foi analisado por um sistema padrão de referência que relaciona a carúncula himenal (ponto fixo) à posição anatômica de seis pontos definidos: 2 na parede vaginal anterior, 2 no ápice vaginal e 2 na parede vaginal posterior. A máxima protrusão do prolapso foi visualizada e registrada durante a manobra de Valsalva solicitada à paciente. Realizou-se a medida do ponto mais externo do prolapso (pontos Ba, Bp e C) comparando-o com a classificação de BW. A medida adotada para avaliar a concordância entre as duas terminologias foi a estatística kappa. RESULTADOS: observou-se correspondência de 100 por cento somente para o prolapso de parede vaginal posterior estádio IV (1 paciente) e para o prolapso uterino estádio zero (29 pacientes), segundo Baden e Walker, com retocele severa e ausência de prolapso, respectivamente. Para os três tipos de prolapsos examinados, os valores da estatística kappa estavam abaixo de 0,4, indicando fraca concordância entre as duas terminologias. Concluímos que existe uma ampla variação nas medidas do ponto mais externo do prolapso ao se realizar a classificação de BW. Para um determinado grau de prolapso na classificação de BW encontramos mais de um estádio na classificação da ICS. CONCLUSÕES: existe fraca concordância entre as classificações de Baden e Walker e a da Sociedade Internacional de Continência para as distopias genitais.