ABSTRACT
OBJECTIVE: To evaluate the safety and effectiveness of endoscopic treatments with Allium® metal ureteric stent (AMUS) for ureteric strictures after kidney transplantation (KT). PATIENTS AND METHODS: In a prospective manner, we gathered clinical data from 68 patients who underwent endoscopic treatments with AMUS for ureteric strictures after KT between January 2019 and March 2022. The definition of surgical success was the unobstructed drainage of the AMUS, or in cases where there was AMUS migration, occlusion or encrustation and subsequently removed, there is no worsening of renal hydronephrosis in the patient during the follow-up period. RESULTS: Based on the specific circumstances of the ureteric strictures, three distinct types of surgery were selected for treatment. The overall success rate of endoscopic treatments for ureteric strictures following KT was 90% (61/68) during a follow-up period of 1 year. Surgical complications included haematuria (18%), pain (10%), urinary tract infections (7.4%), and lower urinary tract symptoms (7.4%). The incidences of stent migration, occlusion, and encrustation were 10%, 2.9%, and 1.5%, respectively. Postoperatively, significant improvements were observed in various parameters. At 1 month after surgery, there was a notable decrease in blood creatinine levels (105.5 vs 90.4 mol/L), urea nitrogen levels (6.6 vs 5.4 mmol/L), and hydronephrosis volume (64.4 vs 43.9 mL). Additionally, the serum estimated glomerular filtration rate increased from 49.5 to 64.4 mL/min/1.73 m2. The follow-up results of patients at 1 year after surgery were similar to those observed at 1 month after surgery. CONCLUSIONS: Systemic endoscopic treatments with AMUS were found to be safe and effective for ureteric strictures after KT with short-term follow-ups. This technique offers a novel option for the treatment of post-KT strictures.
ABSTRACT
Potentiation of the effects of currently available antibiotics is urgently required to tackle the rising antibiotics resistance. The pyruvate (P) cycle has been shown to play a critical role in mediating aminoglycoside antibiotic killing, but the mechanism remains unexplored. In this study, we investigated the effects of intermediate metabolites of the P cycle regarding the potentiation of gentamicin. We found that α-ketoglutarate (α-KG) has the best synergy with gentamicin compared to the other metabolites. This synergistic killing effect was more effective with aminoglycosides than other types of antibiotics, and it was effective against various types of bacterial pathogens. Using fish and mouse infection models, we confirmed that the synergistic killing effect occurred in vivo. Furthermore, functional proteomics showed that α-KG downregulated thiosulphate metabolism. Upregulation of thiosulphate metabolism by exogenous thiosulphate counteracted the killing effect of gentamicin. The role of thiosulphate metabolism in antibiotic resistance was further confirmed using thiosulphate reductase knockout mutants. These mutants were more sensitive to gentamicin killing, and less tolerant to antibiotics compared to their parental strain. Thus, our study highlights a strategy for potentiating antibiotic killing by using a metabolite that reduces antibiotic resistance.
Subject(s)
Anti-Bacterial Agents , Gentamicins , Ketoglutaric Acids , Anti-Bacterial Agents/pharmacology , Animals , Ketoglutaric Acids/metabolism , Ketoglutaric Acids/pharmacology , Mice , Gentamicins/pharmacology , Drug Synergism , Microbial Sensitivity Tests , Bacteria/drug effects , Bacteria/genetics , Bacteria/metabolism , Down-Regulation/drug effects , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Disease Models, AnimalABSTRACT
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.
Subject(s)
Cystitis, Interstitial , Hyaluronic Acid , Female , Humans , Male , Antiviral Agents/therapeutic use , Cystitis, Interstitial/drug therapy , Hyaluronic Acid/therapeutic use , Interferons/therapeutic use , Pain , Adult , Middle AgedABSTRACT
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.
Subject(s)
Cystitis, Interstitial , Toll-Like Receptor 3 , Urothelium , Animals , Female , Humans , Mice , Cell Differentiation , Cell Proliferation , Cystitis, Interstitial/pathology , Cystitis, Interstitial/metabolism , Cystitis, Interstitial/genetics , Mice, Inbred C57BL , Signal Transduction , Single-Cell Analysis , Toll-Like Receptor 3/metabolism , Toll-Like Receptor 3/genetics , Urinary Bladder/pathology , Urinary Bladder/metabolism , Urothelium/pathology , Urothelium/metabolismABSTRACT
OBJECTIVE: To identify the causal role of sodium-glucose cotransporter 2 (SGLT2) inhibition on three urological cancers. METHODS: Six single nucleotide polymorphisms associated with the expression level of SLC5A2, a proxy for SGLT2 inhibition, from a recent publication were extracted. Three common urological cancers, including bladder cancer, prostate cancer and kidney cancer, were analysed. The main cohort of bladder cancer was derived from UK Biobank (1279 cases and 372,016 controls). The prostate cancer cohort was from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium (79,148 cases and 61,106 controls). The kidney cancer phenotype was from the UK Biobank cohort of 463,010 individuals (1114 cases and 461,896 controls). Primary and sensitivity analysis were performed to validate the results. In vitro analysis was also incorporated to validate the Mendelian randomisation results. RESULTS: In primary analysis, SGLT2 inhibition was associated with reduced risk of bladder cancer (OR: 0.98, 95% CI: 0.97-0.99) per unit lowering of HbA1c level. A protective association was also observed for prostate cancer with odds ratio = 0.31 (95% CI = 0.21-0.47). However, we did not discover a causal relationship between SGLT2 inhibition and kidney cancer (OR: 1.00, 95% CI: 0.99-1.00). Sensitivity analysis and in vitro validation did not support the causal role of SGLT2 inhibition in increasing cancer risk. CONCLUSIONS: We did not find any evidence that SGLT2 inhibition could increase the risk of the three cancers. Even in some analysis, SGLT2 inhibition tended to show protective effects on the three urological cancers.
Subject(s)
Kidney Neoplasms , Prostatic Neoplasms , Urinary Bladder Neoplasms , Urologic Neoplasms , Male , Humans , Sodium-Glucose Transporter 2/genetics , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/genetics , Urologic Neoplasms/epidemiology , Urologic Neoplasms/genetics , Urologic Neoplasms/complications , Urinary Bladder Neoplasms/epidemiology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/complications , Kidney Neoplasms/epidemiology , Kidney Neoplasms/genetics , Kidney Neoplasms/complicationsABSTRACT
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.
ABSTRACT
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.
Subject(s)
Suburethral Slings , Urinary Incontinence, Stress , Female , Humans , Urinary Incontinence, Stress/surgery , Urinary Incontinence, Stress/etiology , Network Meta-Analysis , Urologic Surgical Procedures/methods , Reoperation , Treatment OutcomeABSTRACT
BACKGROUND: Metal ureteral stents (MUS) has gained popularity as an endoscopic treatment alternative for the management of ureteral strictures. The aim of this study was to evaluate the safety, efficacy, and tolerability of MUS for treating ureteral strictures and to identify any factors that could influence the success of this intervention. METHODS: This study is a prospective analysis of the efficacy and safety of MUS for treating ureteral strictures in a single-center setting. The study enrolled 246 patients who had been diagnosed with ureteral strictures and had undergone MUS placement between January 2019 and July 2021. The patients were followed-up for a duration of 2 years. RESULTS: The overall success rate of MUS placement was 71.7%. Furthermore, the success rate of ureteral strictures after kidney transplantation (78.2%) was significantly higher than common ureteral strictures (73.0%) or recurrent ureteral strictures (67.6%). Additionally, postsurgery, there was a considerable reduction in hydronephrosis volume (68.9±96.1 vs. 32.1±48.8 cm 3 ), blood creatinine level (103.7±49.8 vs. 94.4±47.5 mol/l) and urea nitrogen level (6.7±7.2 vs. 5.1±2.4 mmol/l). The study also reported that the rate of adverse events associated with MUS was relatively low, included hematuria (7.9%), pain (6.8%), urinary tract infection (6.4%), and lower urinary tract symptoms (5.3%). CONCLUSIONS: MUS appear to be a safe and effective treatment option for ureteral strictures, with a high success rate and low complication rate. These results have important implications for the management of ureteral strictures and can help guide clinical decision-making in the selection of treatment options.
Subject(s)
Ureteral Obstruction , Humans , Constriction, Pathologic/surgery , Constriction, Pathologic/complications , Ureteral Obstruction/etiology , Ureteral Obstruction/surgery , Treatment Outcome , Endoscopy/adverse effects , Stents/adverse effectsABSTRACT
BACKGROUND: The purpose of this study was to evaluate the effects of ß-adrenoceptors (ADRBs) on the urothelial inflammation and zonula occludens (ZO) in a rat PBOO model and in an in vitro model. METHODS: The PBOO model was established by ligating the bladder neck of rats. Twenty rats were divided into 4 groups: sham operation, PBOO + normal saline, PBOO + ADRB2 agonist, PBOO + ADRB3 agonist. PBOO rats were with treated with ADRBs agonists for 3 weeks. Human urothelial cells (HUCs) were subjected to ADRBs agonist treatment or hydrostatic pressure in an in vitro model. RESULTS: In the PBOO group, there was a significant increase in the expression of MCP-1, IL-6 and RANTES compared to the sham group. By contrast, there was a post-PBOO decline in the expression of ZO-1 and ZO-2 in the urothelium. ADRB2 or ADRB3 agonists exhibited downregulated inflammatory cytokine expression and increased ZO expression in the PBOO model. The regulation of inflammation and ZO by ADRB2 and ADRB3 agonists in an in vitro model was found consistent with that in the PBOO model. Moreover, RhoA and ROCK inhibitors suppressed the expression of hydrostatic pressure-induced inflammatory cytokines. Additionally, RhoA agonist reversed the inhibitory effect of ADRBs agonists on the inflammatory secretion from HUCs. CONCLUSIONS: ADRB2 and ADRB3 agonists increased ZO protein expression in HUCs in a rat PBOO model and in an in vitro model. Furthermore, ADRB2 and ADRB3 agonists inhibited the secretion of inflammatory cytokines from HUCs by regulating the RhoA/ROCK signaling pathways.
Subject(s)
Tight Junctions , Urinary Bladder Neck Obstruction , Rats , Humans , Animals , Tight Junctions/metabolism , Urinary Bladder Neck Obstruction/metabolism , Urothelium/metabolism , Inflammation/metabolism , Cytokines/metabolism , Disease Models, Animal , Receptors, Adrenergic, beta-3/metabolismABSTRACT
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.
Subject(s)
Cystitis, Interstitial , MicroRNAs , Humans , Cystitis, Interstitial/genetics , RNA, Circular/genetics , Inflammation , Biomarkers , MicroRNAs/genetics , RNA, Messenger/geneticsABSTRACT
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.
ABSTRACT
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.
Subject(s)
Actomyosin , Calcium , Humans , Actomyosin/metabolism , Calcium/metabolism , Fibroblasts/metabolism , Fibrosis , Myosin Type II/metabolismABSTRACT
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.
Subject(s)
Adaptor Proteins, Signal Transducing , Mechanotransduction, Cellular , Mechanotransduction, Cellular/physiology , Adaptor Proteins, Signal Transducing/metabolism , Trans-Activators , Intracellular Signaling Peptides and Proteins/metabolism , Transcription FactorsABSTRACT
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.
Subject(s)
Cystitis, Interstitial , Urinary Retention , Humans , Urinary Bladder/surgery , Fibrinolytic Agents/adverse effects , Retrospective Studies , Urinary Retention/complications , Cystitis, Interstitial/complicationsABSTRACT
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.
Subject(s)
Botulinum Toxins, Type A , Urinary Bladder, Neurogenic , Urinary Bladder, Overactive , Humans , Adult , Female , Botulinum Toxins, Type A/adverse effects , Quality of Life , Network Meta-Analysis , Muscarinic Antagonists/therapeutic use , Urinary Bladder, Neurogenic/chemically induced , Urinary Bladder, Neurogenic/drug therapy , Urinary Bladder, Overactive/drug therapy , Urinary Bladder, Overactive/chemically induced , Treatment Outcome , Receptors, Adrenergic/therapeutic use , Tibial NerveABSTRACT
Bladder outlet obstruction (BOO) is a prevalent condition arising from urethral stricture, posterior urethral valves, and benign prostatic hyperplasia. Long-term obstruction can lead to bladder remodeling, which is characterized by inflammatory cell infiltration, detrusor hypertrophy, and fibrosis. Until now, there are no efficacious therapeutic options for BOO-induced remodeling. Tetrahedral framework nucleic acids (tFNAs) are a type of novel 3D DNA nanomaterials that possess excellent antifibrotic effects. Here, to determine the treatment effects of tFNAs on BOO-induced remodeling is aimed. Four single-strand DNAs are self-assembled to form tetrahedral framework DNA nanostructures, and the antifibrotic effects of tFNAs are investigated in an in vivo BOO animal model and an in vitro transforming growth factor beta1 (TGF-ß1)-induced fibrosis model. The results demonstrated that tFNAs could ameliorate BOO-induced bladder fibrosis and dysfunction by inhibiting M2 macrophage polarization and the macrophage-myofibroblast transition (MMT) process. Furthermore, tFNAs regulate M2 polarization and the MMT process by deactivating the signal transducer and activator of transcription (Stat) and TGF-ß1/small mothers against decapentaplegic (Smad) pathways, respectively. This is the first study to reveal that tFNAs might be a promising nanomaterial for the treatment of BOO-induced remodeling.
Subject(s)
Nucleic Acids , Urinary Bladder Neck Obstruction , Animals , Urinary Bladder , Transforming Growth Factor beta1/pharmacology , Transforming Growth Factor beta1/metabolism , Nucleic Acids/metabolism , Myofibroblasts/metabolism , Urinary Bladder Neck Obstruction/drug therapy , Urinary Bladder Neck Obstruction/metabolism , FibrosisABSTRACT
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.
Subject(s)
Pelvic Organ Prolapse , Sutures , Female , Humans , Gynecologic Surgical Procedures/adverse effects , Gynecologic Surgical Procedures/methods , Pelvic Organ Prolapse/surgery , Prolapse , Surgical Mesh/adverse effects , Sutures/adverse effects , Treatment OutcomeABSTRACT
PURPOSE: We aimed to analyze the diagnostic value of transperineal ultrasound in patients with stress urinary incontinence (SUI) using evidence-based methods. METHODS: A comprehensive search of the studies on the diagnosis of SUI by transperineal ultrasound in PubMed, EMBASE, MEDLINE, Cochrane library, Medicine, Web of Science, and clinicaltrials.gov databases on August 1, 2022. Studies were included if they met the inclusion criteria and were evaluated by different quality evaluation methods according to study types. Various ultrasound parameters were collected and counted to analyze and judge the diagnostic value of transperineal ultrasound in SUI patients. RESULTS: A total of 13 studies with 1563 participants were finally included. The combined statistics showed no significant difference in age and parity among the included patients, and the BMI of the SUI group was slightly higher than that of the normal population (MD 1.20, 95%CI 0.68-1.72). The results indicated that compared with the normal population, the α angle (MD 15.56, 95%CI 9.93-21.90), ß angle (at rest: MD 10.02 mm, 95%CI 1.95-18.09; at Valsalva: MD 22.40 mm, 95%CI 13.79-31.01), bladder neck descent (MD 6.82 mm, 95%CI 4.49-9.14), area of hiatus (MD 2.83 cm2, 95%CI 0.71-4.94) and bladder neck funneling (RR 4.71, 95%CI 1.08-20.62) of SUI patients were significantly different, which illustrated the potential value of transperineal ultrasound in diagnosing SUI. CONCLUSION: Evidence-based medicine was applied to statistically analyze published articles on the diagnostic value of transperineal ultrasound in SUI. The results suggested that transperineal ultrasound had application value in the diagnosis of SUI and had the potential to become a routine examination method to assist clinical decision-making.