Intravesical Interferon Therapy vs Hyaluronic Acid for Pain Among Female Individuals With Interstitial Cystitis: A Randomized Clinical Trial.

Importance: Interstitial cystitis (IC) is a debilitating condition. Although viral infection is a potential etiological cause, few studies have detected the effect of antiviral treatment. Objective: To determine the efficacy and safety of intravesical interferon instillation compared with hyaluronic acid in female patients with IC. Design, Setting, and Participants: This double-masked, randomized phase 2/3 clinical trial with parallel group design was implemented from October 2022 to April 2023 and had a 6-month follow-up period. The study was conducted at a single center. Eligible participants were female patients aged 18 to 70 years with a diagnosis of IC for more than 6 months. The last visit took place in October 2023. Data were analyzed between October and November 2023. Intervention: Patients were randomized 1:1 to receive either intravesical instillation of interferon or hyaluronic acid. Main Outcomes and Measures: The primary end point was change in visual analog scale pain score. Secondary end points included changes in voiding frequency, functional bladder capacity, symptom index, and global response assessment. Adverse events were closely monitored. Results: Among the 52 patients, the mean (SD) age was 50.0 (14.1) years and they were randomized to either the interferon group (26 [50%]) or hyaluronic acid (26 [50%]). The visual analog pain score showed the interferon group decreased more significantly than hyaluronic acid (-1.3; 95% CI, -2.3 to -0.3; P = .02) at month 6, with 20 patients (77%) exhibiting a 30% or higher reduction in pain compared with baseline. Secondary end points of voiding frequency, functional bladder capacity, and nocturia episodes showed no significant difference between 2 therapies. However, interferon showed a significantly higher reduction in the Interstitial Cystitis Symptom Index (-3.0; 95% CI, -5.3 to -0.7; P = .01) and the Problem Index (-2.5; 95% CI, -4.5 to -0.4; P = .02) at month 6, with 22 patients (85%) presenting as moderately or markedly improved. The frequencies of adverse events were similar between 2 groups. Only 1 patient discontinued hyaluronic acid because of poor effectiveness. Conclusions and Relevance: In this randomized clinical trial, female patients with IC could benefit from intravesical interferon therapy, without serious adverse events. These results offered hope for antiviral approaches in IC, but larger-scale, multicenter trials and long-term follow-up should be considered. Trial Registration: ClinicalTrials.gov Identifier: NCT05912946.

UPK3A+ umbrella cell damage mediated by TLR3-NR2F6 triggers programmed destruction of urothelium in Hunner-type interstitial cystitis/painful bladder syndrome.

Urothelial damage and barrier dysfunction emerge as the foremost mechanisms in Hunner-type interstitial cystitis/bladder pain syndrome (HIC). Although treatments aimed at urothelial regeneration and repair have been employed, their therapeutic effectiveness remains limited due to the inadequate understanding of specific cell types involved in damage and the lack of specific molecular targets within these mechanisms. Therefore, we harnessed single-cell RNA sequencing to elucidate the heterogeneity and developmental trajectory of urothelial cells within HIC bladders. Through reclustering, we identified eight distinct clusters of urothelial cells. There was a significant reduction in UPK3A+ umbrella cells and a simultaneous increase in progenitor-like pluripotent cells (PPCs) within the HIC bladder. Pseudotime analysis of the urothelial cells in the HIC bladder revealed that cells faced challenges in differentiating into UPK3A+ umbrella cells, while PPCs exhibited substantial proliferation to compensate for the loss of UPK3A+ umbrella cells. The urothelium in HIC remains unrepaired, despite the substantial proliferation of PPCs. Thus, we propose that inhibiting the pivotal signaling pathways responsible for the injury to UPK3A+ umbrella cells is paramount for restoring the urothelial barrier and alleviating lower urinary tract symptoms in HIC patients. Subsequently, we identified key molecular pathways (TLR3 and NR2F6) associated with the injury of UPK3A+ umbrella cells in HIC urothelium. Finally, we conducted in vitro and in vivo experiments to confirm the potential of the TLR3-NR2F6 axis as a promising therapeutic target for HIC. These findings hold the potential to inhibit urothelial injury, providing promising clues for early diagnosis and functional bladder self-repair strategies for HIC patients. © 2024 The Pathological Society of Great Britain and Ireland.

Single-cell transcriptomics reveal the remodeling landscape of bladder in patients with obstruction-induced detrusor underactivity.

Detrusor underactivity (DUA) is a common and thorny problem in urology, which severely impairs patients' bladder function and quality of life. However, its underlying pathophysiological mechanism remains unclear. Hence, we sequenced 69,973 cells from five controls and nine patients with bladder dysfunction using single-cell RNA sequencing. Twelve distinct cell types were identified and they showed high cellular and functional heterogeneity among each group. Among them, fibroblasts, macrophages, and epithelial cells had the most intercellular communications. Their aberrant gene expressions and altered intercellular interactions were mainly involved in extracellular matrix organization, inflammation/immune regulation, and cellular injury. Further re-cluster analysis revealed an accumulation of the RBFOX1+ fibroblasts and RIPOR2+ macrophages in dysfunctional bladder wall, which mediated bladder remodeling through dysfunctional extracellular matrix organization and inflammation/immune reaction. Besides, the subtype of the epithelial cells was significantly altered. They underwent an intricate process including inflammation, damage, and repair during bladder remodeling. Overall, this work constructed the first single-cell atlas for obstruction-induced DUA, which could provide a valuable resource for deciphering the cellular heterogeneity and function changes in DUA, as well as potential strategies for bladder function improvement.

Crosstalk between fibroblasts and immunocytes in fibrosis: From molecular mechanisms to clinical trials.

BACKGROUND: The impact of fibroblasts on the immune system provides insight into the function of fibroblasts. In various tissue microenvironments, multiple fibroblast subtypes interact with immunocytes by secreting growth factors, cytokines, and chemokines, leading to wound healing, fibrosis, and escape of cancer immune surveillance. However, the specific mechanisms involved in the fibroblast-immunocyte interaction network have not yet been fully elucidated. MAIN BODY AND CONCLUSION: Therefore, we systematically reviewed the molecular mechanisms of fibroblast-immunocyte interactions in fibrosis, from the history of cellular evolution and cell subtype divisions to the regulatory networks between fibroblasts and immunocytes. We also discuss how these communications function in different tissue and organ statuses, as well as potential therapies targeting the reciprocal fibroblast-immunocyte interplay in fibrosis. A comprehensive understanding of these functional cells under pathophysiological conditions and the mechanisms by which they communicate may lead to the development of effective and specific therapies targeting fibrosis.

A monomeric structure of human TMEM63A protein.

OSCA/TMEM63 is a newly identified family of mechanically activated (MA) ion channels in plants and animals, respectively, which convert physical forces into electrical signals or trigger intracellular cascades and are essential for eukaryotic physiology. OSCAs and related TMEM16s and transmembrane channel-like (TMC) proteins form homodimers with two pores. However, the molecular architecture of the mammalian TMEM63 proteins remains unclear. Here we elucidate the structure of human TMEM63A in the presence of calcium by single particle cryo-EM, revealing a distinct monomeric architecture containing eleven transmembrane helices. It has structural similarity to the single subunit of the Arabidopsis thaliana OSCA proteins. We locate the ion permeation pathway within the monomeric configuration and observe a nonprotein density resembling lipid. These results lay a foundation for understanding the structural organization of OSCA/TMEM63A family proteins.

Long-term outcomes of surgical interventions for stress urinary incontinence: a systematic review and network meta-analysis.

BACKGROUND: Stress urinary incontinence is common among women, and surgical interventions have significantly improved patients' symptoms. The long-term effectiveness of these surgeries is increasingly drawing attention, yet it remains sparsely documented in the literature. OBJECTIVE: To compare the long-term effectiveness and safety of retropubic tension-free vaginal tape (TVT-RP), tension-free vaginal tape-obturator (TVT-O), transobturator tape (TOT), single-incision sling (SIS), Burch colposuspension, and pubovaginal sling (PVS). METHODS: A comprehensive and systematic literature review was conducted in PubMed, EMBASE, MEDLINE, Cochrane Library, Medicine, and clinicaltrials.gov from inception to May 2023. Selected trials were evaluated for potential bias using the Cochrane tool. Treatment modalities were compared using network meta-analysis to assess objective success rate, subjective success rate, and complications as outcomes. RESULTS: A total of 37 studies involving 5720 patients were included. No significant statistical differences were found among the interventions regarding objective success rate. PVS had the highest surface under the cumulative ranking curve SUCRA value (93.1). For subjective success rate, TVT-RP, TVT-O, and PVS demonstrated superiority over SIS, with PVS having the highest SUCRA value (80.1). SIS had lower overall complication and pain rates compared to other methods, with statistical significance. There were no differences in reoperation rate, exposure rate, and urinary tract infection occurrence among the surgical approaches. CONCLUSIONS: In terms of long-term effectiveness and safety, TVT-RP and TVT-O appear to be the preferred options for patients opting for synthetic slings, while for patients seeking nonsynthetic slings, PVS may represent the optimal choice.

The design and evaluation of a quick checklist for urodynamic quality control: A prospective single-center small sample study.

PURPOSE: To design a quick checklist for urodynamic study (UDS), aiming to reduce the occurrence of errors in the process, which may help to increase the quality of UDS. And further to analyze the effectiveness of this quick checklist for UDS quality control. METHODS: First, a quick checklist for uroflow study and pressure-flow study was developed, based on the International Continence Society-Good Urodynamic Practice standards, our previous studies, and recent literature, as well as expert suggestions. Then, patients who underwent UDS between January 2023 to February 2023 were randomly assigned to a study group or a control group. For the study group, the quick checklist was used throughout the UDS process, while the control group did not. The main artefacts were chosen to verify the effectiveness of the quick checklist for improving the UDS quality. RESULTS: The quick checklist comprised three subtypes: checklist for patients, checklist for environment and device, and checklist for UDS test process. 38 UDS traces per group were included. The incidence of missing the standard cough test decreased significantly from 18.4% to 0 (p = 0.012), with the checklist implementation. The baseline drift frequency rate also declined significantly from 39.5% to 5.3% (p < 0.05). Volume < 150 mL on uroflow study occurred in 68.4% of cases and its frequency rate decreased significantly with checklist implementation (p < 0.05). CONCLUSION: A quick checklist for quality control of UDS was developed. The quick checklist as a convenient, quick, and easy used urodynamic quality control method, may help to reduce the technical artefacts and improve fundamental urodynamic quality control. Future research with a larger sample size is needed to confirm the effectiveness of the checklist.

Identification of circRNA-miRNA-mRNA network as biomarkers for interstitial cystitis/bladder pain syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a long-lasting and incapacitating disease, and the exact factors that affect its onset and advancement are still uncertain. Thus, the main aim was to explore new biomarkers and possible therapeutic targets for IC/BPS. Next-generation high-throughput sequencing experiments were performed on bladder tissues. Based on the interactions between circRNA and miRNA, as well as miRNA and mRNA, candidates were selected to build a network of circRNA-miRNA-mRNA. The STRING database and Cytoscape software were utilized to build a protein-protein interaction (PPI) network to pinpoint the hub genes associated with IC/BPS. The expression levels of circRNA and miRNA in the network were confirmed through quantitative polymerase chain reaction. Western blot was applied to confirm the stability of the lipopolysaccharide-induced IC/BPS model, and the effect of overexpression of circ.5863 by lentivirus on inflammation. Ten circRNA-miRNA interactions involving three circRNAs and six miRNAs were identified, and IFIT3 and RSAD2 were identified as hub genes in the resulting PPI network with 19 nodes. Circ.5863 showed a statistically significant decrease in the constructed model, which is consistent with the sequencing results, and overexpression via lentiviral transfection of circ.5863 was found to alleviate inflammation damage. In this study, a circRNA-miRNA-mRNA network was successfully constructed, and IFIT3 and RSAD2 were identified as hub genes. Our findings suggest that circ.5863 can mitigate inflammation damage in IC/BPS. The identified marker genes may serve as valuable targets for future research aimed at developing diagnostic tools and more effective therapies for IC/BPS.

A Y-shape connection device for pediatric patients with an indwelling catheter (Dia = 8Fr) during urodynamic studies, especially for filling phase measurements: a single-center prospective study for safety and effectiveness.

Introduction: This prospective study aimed to assess the effectiveness of a Y-shape connection device in reducing pain and bleeding in pediatric patients with indwelling catheters during urodynamic studies (UDS), while also obtaining effective results in the filling phase. Methods: A total of 45 pediatric patients with a mean age of 13 years were included, all of whom underwent both a UDS with the Y-shape connection device (Method A) and a standard UDS procedure (Method B). Results: The Y-shape connection device demonstrated similar overall urodynamic parameters compared to the standard procedure, while also resulting in significantly less bleeding (P = 0.006) and lower VAS scores during (1.12 ± 0.58 vs. 3.88 ± 1.01, P = 0.001) and after (0.12 ± 0.08 vs 2.91 ± 0.89, P = 0.001) the procedure. No adverse events were reported at the 1-month follow-up. Discussion: These findings suggest that the Y-shape connection device can effectively reduce pain and bleeding during and after UDS in pediatric patients with indwelling catheters (Dia = 8Fr), while also obtaining effective results in the filling phase. Therefore, this Y-shape connection device has a more significant value for children who require urodynamic studies and place more emphasis on filling phase parameters. Clinical trial registration: ChiCTR2300068280.

Actomyosin Activity and Piezo1 Activity Synergistically Drive Urinary System Fibroblast Activation.

Mechanical cues play a crucial role in activating myofibroblasts from quiescent fibroblasts during fibrosis, and the stiffness of the extracellular matrix is of significant importance in this process. While intracellular force mediated by myosin II and calcium influx regulated by Piezo1 are the primary mechanisms by which cells sense and respond to mechanical forces, their intercellular mechanical interaction remains to be elucidated. Here, hydrogels with tunable substrate are used to systematically investigate the crosstalk of myosin II and Piezo1 in fibroblast to myofibroblast transition (FMT). The findings reveal that the two distinct signaling pathways are integrated to convert mechanical stiffness signals into biochemical signals during bladder-specific FMT. Moreover, it is demonstrated that the crosstalk between myosin II and Piezo1 sensing mechanisms synergistically establishes a sustained feed-forward loop that contributes to chromatin remodeling, induces the expression of downstream target genes, and ultimately exacerbates FMT, in which the intracellular force activates Piezo1 by PI3K/PIP3 pathway-mediated membrane tension and the Piezo1-regulated calcium influx enhances intracellular force by the classical FAK/RhoA/ROCK pathway. Finally, the multifunctional Piezo1 in the complex feedback circuit of FMT drives to further identify that targeting Piezo1 as a therapeutic option for ameliorating bladder fibrosis and dysfunction.

Correlation between obesity-related measurements and initial and initial resting intravesical and abdominal pressures in urodynamic study using air-filled catheter system.

OBJECTIVES: To establish the initial (before pressure equilibrium) and initial resting intravesical and abdominal pressure in the sitting position using air-filled catheters, to assess the correlation between these pressures and obesity-related measurements, and to estimate if obesity-related measurements can be a guide to interpret initial and initial resting pressures in urodynamic testing. METHODS: Patients with non-neurogenic lower urinary tract symptoms referred for urodynamic testing in our center were consecutively enrolled in a prospective study from August 2022 to October 2022. The correlation between the initial and initial resting pressures (before and after pressure equilibrium) and obesity-related measurements were analyzed using Pearson's correlation coefficient and multiple linear regression analysis. RESULTS: Ninety-eight patients aged 56 ± 16 were studied. The 95% range of the initial intravesical and abdominal pressure were 18-42 cmH2 O and 21-60 cmH2 O, respectively. The initial resting intravesical, abdominal, and detrusor pressure in the 95% range were 17-41, 16-42, and -5 to 4 cmH2 O, respectively. Over the multiple analysis, abdominal fat thickness, and body mass index (BMI) correlated independently with initial intravesical pressure, and only visceral fat grade correlated with initial abdominal pressure. BMI correlated independently with initial resting intravesical pressure. CONCLUSIONS: Our results determined the ranges of values of both initial and initial resting pressures in the air-charged system. Meanwhile, the present study indicated the obesity-related measurements may be used as a guide to interpret the initial and initial resting pressures in urodynamic testing, and may provide a reference for the quality control of these pressures.

Evaluation of the effectiveness of four alternative approaches for the classical cough test during a urodynamic study in the context of the COVID-19 global pandemic.

BACKGROUD: To evaluate four different alternatives to the classical cough test during a urodynamic study in the context of the COVID-19 pandemic. METHODS: Patients who needed to undergo a urodynamic study (UDS) at the West China Hospital of Sichuan University between April 2021 and May 2021 were randomly selected according to the inclusion and exclusion criteria. During the UDS process, we used four alternative methods to the "cough test": 1) quickly pressing the bladder area, 2) performing the Valsalva maneuver, 3) performing the Kegel maneuver, and 4) letting the patient close their mouth while performing the cough test. The "cough" waveform amplitudes and characteristics of the graphics were obtained and compared with the classical cough test. RESULTS: A total of 120 patients (89 men, 31 women) were included in the study. There was no significant difference between the cough waveform amplitude induced by the Valsalva maneuver compared with the classical cough test (P = 0.182); there was no significant difference between the cough waveform amplitude induced by the cough test with the mouth closed and the classical cough test (P = 0.342); there was no significant difference between pressing quickly on the bladder area and the classical method (P = 0.076); and there was a significant difference between the data obtained by the Kegel maneuver and the classical method (P < 0.05). The average "cough" amplitudes obtained were 73.14 ± 22.48 cm H2O, 66.17 ± 17.12 cm H2O, 82.93 ± 18.95 cm H2O, 26.50 ± 8.68 cm H2O, and 68.90 ± 20.32 cm H2O by the classical cough test, by quickly pressing the bladder area, by the Valsalva maneuver, by the Kegel maneuver, and by coughing with a closed mouth, respectively. CONCLUSION: Quickly pressing the bladder area, performing the Valsalva maneuver, and letting the patient close their mouth while performing the cough test can all provide effective cough waveforms and amplitudes. TRIAL REGISTRATION: No. 2021-183.

Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets.

Cellular mechanotransduction, a critical regulator of numerous biological processes, is the conversion from mechanical signals to biochemical signals regarding cell activities and metabolism. Typical mechanical cues in organisms include hydrostatic pressure, fluid shear stress, tensile force, extracellular matrix stiffness or tissue elasticity, and extracellular fluid viscosity. Mechanotransduction has been expected to trigger multiple biological processes, such as embryonic development, tissue repair and regeneration. However, prolonged excessive mechanical stimulation can result in pathological processes, such as multi-organ fibrosis, tumorigenesis, and cancer immunotherapy resistance. Although the associations between mechanical cues and normal tissue homeostasis or diseases have been identified, the regulatory mechanisms among different mechanical cues are not yet comprehensively illustrated, and no effective therapies are currently available targeting mechanical cue-related signaling. This review systematically summarizes the characteristics and regulatory mechanisms of typical mechanical cues in normal conditions and diseases with the updated evidence. The key effectors responding to mechanical stimulations are listed, such as Piezo channels, integrins, Yes-associated protein (YAP) /transcriptional coactivator with PDZ-binding motif (TAZ), and transient receptor potential vanilloid 4 (TRPV4). We also reviewed the key signaling pathways, therapeutic targets and cutting-edge clinical applications of diseases related to mechanical cues.

Association between urinary phthalate metabolites and nephrolithiasis in adults: A cross-sectional analysis with NHANES 2007-2018.

Nephrolithiasis is highly prevalent and brings health and economic burdens to patients. The augmentation of nephrolithiasis may be associated with exposure to phthalate metabolites. However, few studies investigated the effect of various phthalates exposure on nephrolithiasis. We analyzed data from 7139 participants aged 20 years or above from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Serum calcium level-stratified univariate and multivariate linear regression analyses were performed to explore the relationship between urinary phthalate metabolites and nephrolithiasis. As a result, the prevalence of nephrolithiasis was approximately 9.96%. After adjusting for confounding factors, associations were found between serum calcium concentration with monoethyl phthalate (P = 0.012) and mono-isobutyl phthalate (P = 0.003) compared with tertile 1 (T1). In adjusted analysis, nephrolithiasis was positively associated with middle and high tertiles of mono benzyl phthalate (P < 0.05) compare with low tertile group. Furthermore, high-level exposure to mono-isobutyl phthalate had a similar positive association with nephrolithiasis (P = 0.028). Our findings provide evidence that exposure to certain phthalate metabolites (i.e. MiBP and MBzP) may be associated with a high risk of nephrolithiasis depending on serum calcium level.

Superior improvement on soil quality by Pennisetum sinese vegetation restoration in the dry-hot valley region, SW China.

Vegetation restoration is a good way to improve soil quality and reduce erosion. However, the impact of vegetation restoration on soil quality in the dry-hot valley region has been overlooked for many years. This study aimed to reveal the effects of Pennisetum sinese (PS) and natural vegetation (NV) on soil quality and then to explore the feasibility of introducing PS for the vegetation restoration of the dry-hot valley region. The PS and NV restoration areas deserted land evolving from cultivated land (CL) have been established since 2011. The results showed that the soil properties were obviously improved by PS from the dry to wet seasons, except for the soil available phosphorous. The comprehensive soil quality indexes of the three typical seasons (dry, dry-wet, and wet) were determined by using nonlinear weighted additive (NLWA) based on the total dataset, significant dataset and minimum dataset (MDS). The results indicated that the comprehensive minimum dataset soil quality index (MDS-SQI) of the three typical seasons evaluate soil quality well. The soil quality of PS was significantly greater than that of CL and NV (P < 0.05), as shown by the MDS-SQI. Additionally, PS could maintain a stable soil quality in the three typical seasons, while both CL and NV had obvious fluctuations. In addition, the result of the generalized linear mode suggested that the vegetation type had the greatest impact on the soil quality (44.51 %). Comprehensively, vegetation restoration in the dry-hot valley region has a positive impact on the soil properties and quality. PS is a great candidate species for the early vegetation restoration in the dry-hot valley region. This work provides a reference for vegetation restoration and rational utilization of soil resources in degraded ecosystems in dry-hot valleys and other soil erosion areas.

Perioperative Safety of Bladder Hydrodistention in Patients on Antithrombotic Therapy.

IMPORTANCE: Bladder hydrodistention (BH) is commonly used to diagnose and treat patients with interstitial cystitis/bladder pain syndrome (IC/BPS), but the overall assessment of bleeding complications for patients taking antithrombotics is lacking. OBJECTIVES: The study aimed to investigate if perioperative complications were more common in patients with IC/BPS receiving antithrombotic therapy after BH. STUDY DESIGN: We retrospectively reviewed patients with IC/BPS who underwent hydrodistention during January 2010 and May 2021. Patients with and without antithrombotic drugs were identified and grouped, and their medical records were reviewed. Perioperative data and symptom scores were assessed. The rates of complications in the 2 groups were recorded at 3 months and at the last visit postoperatively. RESULTS: A total of 387 patients were eventually included. Among them, 29 (7.5%) patients were receiving systemic antithrombotic therapy and 358 (92.5%) were not. Compared with the non-antithrombotic group, patients receiving antithrombotic therapy demonstrated a longer hospital stay ( P = 0.033) and a longer catheterization time ( P = 0.034). Moreover, the patients with antithrombotic drugs had increased odds of bladder tamponade (odds ratio, 6.76; P = 0.019) and urinary retention (odds ratio, 5.79; P = 0.033) both 3 months postoperatively and last follow-up, but this is not statistically different between patients with and without Hunner lesions. No thromboembolic events were identified during the study period. CONCLUSIONS: Although a small number of patients with IC/BPS needed anticoagulants, longer hospital stays, longer catheterization time, and increased odds of bladder tamponade and urinary retention were observed in patients receiving antithrombotic therapy. Still, a comprehensive management scheme to balance bleeding complications and antithrombotic agents is needed for individuals.

The effectiveness and safety of oral medications, onabotulinumtoxinA (three doses) and transcutaneous tibial nerve stimulation as non or minimally invasive treatment for the management of neurogenic detrusor overactivity in adults: a systematic review and network meta-analysis.

BACKGROUND: Oral medications, onabotulinumtoxinA injections, and transcutaneous tibial nerve stimulation (TTNS) are recommended by the American Urological Association/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction guidelines as non or minimally invasive treatments for patients with neurogenic detrusor overactivity (NDO) without treatment hierarchy. OBJECTIVE: The objective was to compare and rank the effectiveness and safety of oral medications, three doses of onabotulinumtoxinA, and TTNS on improving urodynamic outcomes in patient-reported outcomes and safety outcomes in patients with NDO. METHODS: The authors searched PubMed, EMBASE, MEDLINE, Cochrane Library, Medicine, and clinicaltrials.gov, from their inception to October 2022 and included randomized controlled studies on the drug, onabotulinumtoxinA, and TTNS for the treatment of patients with NDO. Outcomes included urodynamic parameters, voiding diary, quality of life changes, adverse event rate and postvoid residual. RESULTS: A total of 26 articles and 2938 patients were included in the statistics. Regarding effectiveness, all interventions except TTNS and α-blockers were statistically different for the placebo group. The urodynamic outcome and patient-reported outcome suggested that onabotulinumtoxinA injection (urodynamic outcome: onabotulinumtoxinA 200 U, the mean surface under the cumulative ranking curve (SUCRA): 87.4; patient-reported outcome: onabotulinumtoxinA 100 U, mean SUCRA: 89.8) was the most effective treatment, and the safety outcome suggested that TTNS (SUCRA: 83.3) was the safest. Cluster analysis found that antimuscarinics and ß3-adrenoceptor-agonists possessed good effectiveness and safety. CONCLUSION: OnabotulinumtoxinA injection is probably the most effective way to treat patients with NDO, with increasing effectiveness but decreasing safety as the dose rises. The effectiveness of α-blockers and TTNS was not statistically different from the placebo group. Antimuscarinics and ß3-adrenoceptor-agonists have good effectiveness and safety.

Comparative study of absorbable suture and permanent suture in sacrocolpopexy: a meta-analysis and systematic review.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to compare the surgical results and the complications of absorbable suture (AS) versus permanent suture (PS) in sacrocolpopexy (SCP). METHODS: We systematically searched PubMed, Embase, ClinicalTrials.gov, and the Cochrane Library Central Register of Controlled Trials for articles in which researchers compared AS with PS in SCP. The primary outcomes were the surgical success rate and suture-related complications (suture exposure/erosion, mesh erosion, and suture removal). All analyses were performed with Review Manager 5.3. RESULTS: Four articles involving 689 patients were ultimately included. Our findings demonstrated that AS had similar surgical success rates to those of PS (OR=1.34; 95% CI, 0.60-2.96) and no significant differences in failure rates were noted between the two groups (OR=0.75; 95% CI, 0.34-1.66). Subgroup analyses in patients with anatomical failure revealed no significant differences in recurrent posterior prolapse (OR=0.33; 95% CI, 0.05-2.10) or in recurrent apical (OR=0.64; 95% CI, 0.03-13.66) or anterior prolapse (OR=0.45; 95% CI, 0.13-1.57). However, the AS group were at a lower risk of suture exposure/erosion (OR=0.18; 95% CI, 0.06-0.58) and a lower suture removal rate (OR=0.14; 95% CI, 0.03-0.61) and retreatment (OR=0.36; 95% CI, 0.16-0.82), but the mesh erosion was not significantly different (OR=1.00; 95% CI, 0.49-2.08). CONCLUSIONS: The data showed that AS had a similar success rate, less exposure/erosion, and were less likely to be removed and require retreatment than PS, which supported the notion that AS is as effective as PS but safer.