Bladder Dysfunction Research Articles

From central to peripheral: A new perspective on bladder dysfunction in Parkinson disease

As opposed to classical overactive (OAB) symptoms, Parkinson disease (PD) patients often exhibit detrusor hyperreflexia and impaired contractility or underactive bladder. OAB would be more related to central nervous system dysfunction, but nerve damage in peripheral ganglia (eg, pelvic ganglia in the bladder wall) may play a mechanism of dysfunction manifesting as underactive bladder in PD. We propose a novel hypothesis regarding neurogenic urologic dysfunction in PD, suggesting a potential involvement of peripheral nervous system dysfunction in addition to central nervous system dysfunction. This hypothesis emphasizes the significance of investigating peripheral neuron damage in the urinary bladder. We hereby review the relevant neurogenic bladder dysfunction associated with PD, compare and contrast OAB and underactive bladder manifestations and dysfunction, and discuss novel considerations toward this disease with great unmet needs.

Professor LU Yonghui 's clinical experience in treatment of female stress urinary incontinence with acupuncture at the acupoints of conception vessel and bladder meridian

The paper introduces professor LU Yonghui's clinical experience in treatment of female stress urinary incontinence. Regarding the pathogenesis of this disease, qi and blood deficiency, and malnutrition of moyuan (sites where the pathogens are hidden, and the membranes outside zangfu organs) are ben (the primary, root cause), while, the dysfunction of qi movement of the triple energizer and dysfunction of bladder in controlling urination are biao (the secondary, symptoms). In treatment, under the guidance of computed tomography, Zhongji (CV 3), the front-mu point of the bladder, is punctured deeply to regulate the functions of zang organ. Qihai (CV 6) and Guanyuan (CV 4) are punctured to tonify the organs and control urine, and back-shu points of the bladder meridian are stimulated to adjust qi movement of the triple energizer. All of the acupoints co-act on nourishing moyuan, activating qi movement of the triple energizer and the bladder to control urination.

THE EFFECT OF THE FIRST INTRADETRUSOR BOTULINUM TOXIN INJECTION ON FUNCTIONAL INDEPENDENCE, QUALITY OF LIFE, PAIN AND SPASMS IN INDIVIDUALS WITH SPINAL CORD INJURY

After a spinal cord injury (SCI) practically all patients experience neurogenic bladder dysfunction. The botulinum toxin type A is a procedure for treating urological complications in these patients. The objective this study was to analyze whether individuals with traumatic SCI have improved functionality, quality of life (QoL), pain, and spasms after the first application of intradetrusor botulinum toxin type A. A prospective longitudinal observational study was developed with twenty patients with traumatic SCI followed up in a rehabilitation center. The patients were evaluated before, one and four months after the first application of intradetrusor botulinum toxin type A. The instruments used were: Spinal Cord Independence Measure III (SCIM III) and Qualiveen-SF, to assess functionality and QoL, respectively; Numeric Rating Scale for pain assessment and the Penn Scale to assess the spasms. Descriptive and inferential (p <0.05) statistics were perfomed. Of the patients evaluated, 90% were men, and 80% had paraplegia. In the first month after applying botulinum toxin type A, there was improvement in the domain related to sphincter control of SCIM III (p=0.02). There was no statistically significant difference in the QoL, pain intensity, frequency and severity of spasms before application of botulinum toxin and after 1 and 4 months (p>0.05). The first application of intradetrusor botulinum toxin type A interfered positively functional independence related to sphincter control in the first month after application, but did not influence the pain, spasm and QoL.

Does Adding TENS to Pelvic Floor Rehabilitation Effect on Urodynamics and Clinical Results in Children With Spina Bifida?

Children with spina bifida (SB) experience a reduced quality of life due to neurogenic bladder dysfunction and the risk of renal failure later in life. Pelvic floor rehabilitation (PFR) and transcutaneous electrical nerve stimulation (TENS) have gained prominence in recent years due to their positive effects in treating different types of bladder issues in both adults and children. Our study aims to investigate the effects of using these two methods together in children with SB and to delineate their potential value for clinical practice. Children with neurogenic bladder dysfunction due to SB who admitted to our spina bifida center were enrolled. Those patients, between 5 and 15 years of age, with only neurogenic detrusor overactivity (NDO) were randomly divided into two groups using an online computer application. While only the PFR was applied to Group PFR (n = 14), TENS was used in addition to this therapy in Group PFR + T (n = 14). The PFR sessions included abdominal massage, strength exercises, diaphragmatic breathing exercises, and contracting pelvic floor muscles. TENS was used in a standard fashion as previously described in patients with SB. Before and after treatment, patients' clinical data, dysfunctional voiding symptom score (DVSS), lower urinary tract symptoms, and quality of life scores due to urinary incontinence were evaluated. Urodynamic outcomes such as detrusor pressure, bladder capacity, contractility, and residual urine amount were also evaluated. Twenty eight children out of 750 SB patients were enrolled in our center. Children with only NDO due to SB were included in the study (Group PFR, mean age 8.3 ± + 2.7 years, 10 boys, four girls; Group PFR + T, 7.86 ± 2.03 years, eight boys, six girls). Treatment duration was 6 weeks (18 sessions). There was a decrease in voiding and lower urinary tract symptoms in both groups regardless of the use of TENS (p < 0.05). Maximum detrusor pressure significantly decreased only in the TENS group after treatment (from 82.143 ± 58.069 cmH2O to 58.077 ± 39.872 cmH2O) (p < 0.05). The difference in clinical parameters, quality of life scores and other urodynamic parameters were not found to be significant between groups. PFR and TENS may be effective in SB with NDO to reduce voiding symptoms, and protect bladder from increased pressures. PFR seems to be a useful conservative approach in patients with NDO, adjunt to standard treatment. Further studies are needed in delineation of a personalized holistic treatment approach in these patients. Addition of TENS to standard PFR in NDO may be effective in reducing maximum detrusor pressures, however, it does not seem to specifically contribute for improving incontinence and incontinence-related quality of life.

Care of children with posterior urethral valves after initial endoscopic incision/ablation: what a nephrologist needs to know.

Posterior urethral valves (PUV) are the most common cause of congenital urethral obstruction and are unique in the challenges they pose in management. Endoscopic ablation/incision of the valves is usually offered as the primary treatment of choice. Following this, a range of different clinical patterns are observed, each with varying bladder dysfunction and continence issues and associated with different grades of chronic kidney disease. This review outlines a systematic approach that could help pediatric nephrologists, pediatricians, and pediatric urologists, as well as nursing and allied health specialists, assess these children and develop well-informed management plans. The need for surveillance for bladder dysfunction (incidence approximately 55%), identification of red flags for progression to kidney failure (incidence approximately 20%), and multidisciplinary approach to care are presented, with a focus on reducing long-term morbidity in patients and difficulties for the families. Where possible, an alternative in resource-constrained situations is suggested. We also briefly outline the role of pharmacotherapy, assisted bladder emptying/drainage, and other interventions that have a role in the medium- to long-term management of these patients.

Bladder Symptoms Prvoked by Short, Rapid Acting Loop Diuretics: A Frequent But Often Overlooked Problem.

Bladder dysfunction entails overactive bladder (OAB) defined as symptoms of urinary urgency, frequency, and/or nocturia with or without incontinence if there is no obvious pathology or infection or lower urinary tract symptoms (LUTS) that includes recognized causes of bladder dysfunction. Literature search. Symptoms of OAB are reported in about 15% of the adult US population. This is increased 2- to 3- fold in patients with congestive heart failure (CHF), hypertension, cardiovascular disease (CVD), chronic kidney disease (CKD) or the elderly where it often accompanies prescription for short, rapid acting loop diuretics. However, less than 2% of patients seeking care for OAB receive treatment. The fear of urinary incontinence from short, rapid acting loop diuretics may contribute to medication nonadherence and less well controlled, apparently resistant hypertension. The bladder contracts to rapid stretch. Thus, less rapid acting diuretics such as thiazides or extended-release formulations of loop diuretics may be preferable for those with bladder dysfunction. Alternatively, the use of a mineralocorticosteroid receptor antagonist, angiotensin receptor antagonist/neprilysin inhibitor or sodium glucose linked transport type 2 inhibitor may allow a reduction in dose of a short, rapid acting loop diuretic for those with bladder dysfunction. A worsening of symptoms from bladder dysfunction by short, rapid acting loop diuretics occurs frequently in patients with CVD, CHF, hypertension and CKD where it can contribute to impaired quality of life and poor adherence and thereby to worsening outcomes.

The Impact of Bladder Dysfunction on Physical Activity in Multiple Sclerosis Using Wearable Technology

The Impact of Bladder Dysfunction on Physical Activity in Multiple Sclerosis Using Wearable Technology

Long-term surgical outcomes of ileovesicostomy at a single children's hospital

IntroductionThe ileovesicostomy (IV) is a surgical option for patients with refractory bladder dysfunction at-risk of upper tract deterioration who cannot catheterize or lack social support for managing an augmentation cystoplasty (AC). Long-term outcomes after IV in children are lacking in the literature. ObjectiveWe assessed the risk of long-term surgical complications in pediatric patients with IV at a single children’s hospital. Study designWe retrospectively reviewed the records of patients undergoing IV between 2002 to 2021 at a single children’s hospital. The primary outcome was the rate of surgical complications in IV patients after initial reconstruction. Specific complications of interest included intra-abdominal, reservoir, and stomal complications, respectively. We also assessed renal outcomes, including the change in glomerular filtration rate (ΔGFR) and Society of Fetal Urology (ΔSFU) hydronephrosis from the time of surgery to last follow up. ResultsThe study comprised 17 IV patients, with most patients having a diagnosis of spina bifida (65%). Median follow-up was 6.4 years. The mean rate of surgical complications per patient year was 0.11 +/- 0.20. On survival analysis, the time to first complication for IV was 84.4 months. The incidence of intra-abdominal, reservoir, and stomal complications over the study period was 2/17 (11.8%) for each of these complication types. The mean ΔSFU grade from the time of surgery to last follow up was -1.24 +/- 1.48 and mean ΔGFR was -2.5 +/- 32.7 ml/min. DiscussionWe found that IV in pediatric patients experience a low rate (0.11/year) of complications and that median time to first complication was 84 months. Additionally, IV offers adequate renal preservation. Our study is limited, though, by its retrospective nature, small sample size, heterogenous population and lack of comparison group. ConclusionOur experience demonstrates that IV has a low rate of surgical complications and preserves renal function. We believe it is a reasonable surgical option for the well selected patient with refractory bladder dysfunction at-risk of upper tract deterioration who is unable to reliably catheterize.

Think Tank 2: How Do We Precisely Define the "High Risk Bladder" and What Are the Interrelationships Between Inflammation, Blood Flow, Fibrosis, and Loss of Bladder Compliance?

Defining "high-risk bladder" or "high-pressure bladder" involves recognizing the potential for an unsafe lower urinary tract, where dysfunction in storage and micturition can threaten upper urinary tract health, leading to unfavorable outcomes like dialysis, recurrent infections, systemic impact, or mortality. ICI-RS was held in Bristol in June 2024, and Think Tank 2 aimed to define research priorities including identifying clinical predictors and developing prevention and monitoring strategies. Risk factors encompass both congenital and neurogenic lower urinary tract dysfunction, bladder outlet obstruction, vascular diseases, and inflammatory disorders, but a validated stratification risk is lacking. Reduced compliance and detrusor overactivity lead to high filling pressures and raised detrusor leak point pressure, playing urodynamic studies a crucial role in risk assessment, though further research is needed for different neurogenic populations. Congenital conditions such as spina bifida, posterior urethral valves, and bladder exstrophy also contribute to a high-risk bladder through fibrosis and reduced compliance. Inflammation and ischemia are key factors, with inflammation leading to fibrosis and impaired bladder storage and voiding function. Novel treatments, including sGC activators, PDE5 inhibitors, and regenerative therapies like stem cell injections and extracorporeal shock wave treatment, show promise in mitigating fibrosis and improving bladder compliance. Identifying and validating clinical risk stratification models, precise biomarkers and therapeutic windows remains essential for effective management and reversal of bladder fibrosis and dysfunction.

Reasons for Hospital Admission in Individuals With Multiple Sclerosis.

Health care utilization is higher in individuals with multiple sclerosis (MS) than in the general population. However, there are limited data on the reasons for their hospital admissions. Our primary objective is to analyze the reasons for the hospitalization of individuals with MS with the goal of identifying preventable causes. We conducted a retrospective analysis of a cohort of adults with a confirmed diagnosis of MS admitted to Duke University Hospital between January 2018 and January 2020. This yielded a cohort of 210 individuals. Data were analyzed using descriptive statistics. The most common reason for admission was urinary tract infection (UTI; 10.3%). The average length of stay was 6.1 days for the individuals with MS vs 5.5 days for the general population. The 30-day readmission rates were 14.9% and 15.5%, respectively. A significant number of admitted patients were not on any disease-modifying therapy (DMT), and no difference in median age was identified between those with a DMT vs those without. Length of stay and readmission rates were similar to those of the general population in this contemporary cohort. Given the prevalence of bladder dysfunction in MS, it is not surprising that a UTI was the most common reason for admission. Actively addressing management of and techniques for bladder dysfunction may decrease the admission rate for individuals with MS. Though we now have more treatment options for MS, many individuals with the highest health care utilization are not on a DMT. Future research is needed to identify the factors that can be addressed to support these patients and reduce preventable hospitalizations.

Assessing the Use of BotulinumtoxinA for Hyperactive Urinary Tract Dysfunction a Decade After Approval: General Versus Local Anesthesia for BotulinumtoxinA Detrusor Injection

Background: The onabotulinumtoxinA detrusor injection (OnabotA DI) was approved a decade ago for the treatment of patients with idiopathic overactive bladder (iOAB) or neurogenic detrusor overactivity (nDO) dysfunction who had not been treated successfully otherwise. The procedure is usually performed under local anesthesia (LA), and various approaches have been investigated to make the procedure as painless as possible. We examined the level of anxiety and pain experienced by patients who wanted to have the procedure performed under LA or general anesthesia (GA). Material and Methods: Patients scheduled for OnabotA DI were able to choose the anesthesia procedure (LA or GA). The Amsterdam Preoperative Anxiety and Information Scale (APAIS) was used to grade anxiety before anesthesia or before the procedure itself. Intra- and postoperative pain was determined using the Visual Analogue Scale (VAS). Various established questionnaires (including the Urinary Distress Inventory UDI-6), as well as a postoperative satisfaction questionnaire, were used to evaluate the success of the therapy. Results: In total, 104 patients (93 F, 11 M; age 64.0 (22–89) years; 80× iOAB, 24× nDO) were evaluated. OnabotA-DI was performed with LA in 72 patients and GA in 32. Stratified by first versus repeat injection in the LA group, there was a significant decrease in the Anxiety Score in the first vs. repeat injection group (p = 0.038). The LA group showed higher concerns in the anesthesia questions of the Amsterdam Preoperative Anxiety and Information Scale (APAIS) than the GA group (OR: 0.29, 95%CI: 0.02–1.74). The VAS Pain Score during the procedure was significantly lower in the GA group compared to the LA group (LA: 3.3 ± 2.2, GA group 1.5 ± 1.5; p &lt; 0.001). There were no differences in the success of therapy. Despite the fear and pain, patients preferred LA to GA. Conclusions: This study shows that the anxiety and pain burden of patients undergoing OnabotA-DI under LA is significant in comparison to GA during the first injection, but insignificant for following injections. Overall, LA is favored over GA.

Disorders in cytokine synthesis in women with uterine fibroids

In the structure of gynecological diseases, uterine fibroids occupy an “honorable” second place after inflammatory processes of the genital organs, and its share reaches 40%. Uterine fibroids are a benign monoclonal tumor that develops from one abnormal smooth muscle cell of the myometrium, which, as a result of mutation, has the ability to grow unregulated. Common symptoms of the disease include pelvic discomfort or pain, excessive uterine bleeding, secondary anemia, infertility, and bowel and bladder dysfunction. Uterine fibroids can negatively affect the general condition of a woman, causing hormonal, vegetative-vascular and psycho-emotional disorders. Moreover, about 80% of patients with uterine fibroids undergo radical surgical treatment. The mechanisms of development and growth of this benign tumor have not been fully established and remain controversial. The role of immune disorders in the pathogenesis of fibroids is currently being discussed. It has been proven that the growth of fibroids is accompanied by a weakening of immune defense against the background of an increase in the level of proinflammatory cytokines, which are regulators of the processes of proliferation and apoptosis, mediators of the action of sex steroids. The aim of the study was to study the level of some pro-inflammatory cytokines (IL-1β, IL-2, TGF-β2 and MCP-1) in the blood serum of women of reproductive age with uterine fibroids, depending on the size and nature of tumor growth. A comparative analysis of the results of examination of 123 women with uterine fibroids, who made up 2 groups: 1st group of 65 women with simple uterine fibroids and 2nd group of 58 women with rapidly growing uterine fibroids, is presented. The examination included a comprehensive clinical and laboratory study. The level of cytokines (IL-1β, IL- 2, TGF-β2, MCP-1) in the blood serum was assessed by ELISA. It was found that in patients of reproductive age with uterine fibroids, there is an increase in the levels of IL-1β, TGF-β2 and MCP-1. In women with rapidly growing uterine fibroids, these changes are more pronounced. The concentration of IL-2 is reduced in all women with uterine fibroids, regardless of the size and nature of tumor growth. It has been established that an increase in the size of myomatous nodes is accompanied by an increase in immune imbalance: there is an increase in the levels of pro-inflammatory cytokines (IL-1β, TGF-β2, MCP-1) against the background of a reduced content of the lymphokine IL-2, which we regard as possible links in the pathogenesis of uterine fibroids. A pronounced deficiency of IL-2 in the blood serum against the background of a sharp increase in the concentration of TGF-β2 and MCP-1 in the blood of women with uterine fibroids can be considered as a negative criterion for predicting disease progression and used as an additional prognostic marker of tumor growth

Surgical Outcomes of Patients with Benign Spinal Tumors: Insights from A Prospective Quasi Experimental Study

Background: Spinal tumor is one of the causes of back pain, sensory motor deficit and bowel bladder dysfunction. Evaluation of postoperative mortality, morbidity and outcomes after resection of spinal cord tumors is critical to the practice of evidencebased medicine. Hence, it is important to carefully examine surgical outcomes at an institutional level. Objectives: The aim of the study was to describe the results of benign spinal tumor after surgical treatment according to location. Materials &amp; Method: This quasi-experimental study was conducted in the Department of Neurosurgery, Chittagong Medical College and Hospital for a period of 12 months. Twenty eight cases of benign spinal tumor underwent surgical treatment were enrolled in the study. Average hospital stay from surgery to discharge was 12-15 days. Postoperative neurological outcome in Frankel’s grade and bowel bladder involvement were assessed from 1st POD to 3rd month after surgery and data were recorded at 7th POD, 1st month and 3rd month after surgery. Collected data were analyzed by using SPSS-23. Results: Among the 28 cases, 15 were men and 13 were women. The mean age was 36.19 (±14.29) years and age range was 15 to 62 years. Twenty three (82.14%) patients improved by at least one Frankel grade and remaining five (17.86%) patients maintained their preoperative Frankel grade. Out of eight (28.6%) cases with absent bowel bladder dysfunction before surgery six (75%) recovered within three months. Postoperative deterioration was not observed in any of the included case. Ten (35.7%) patients had excellent outcome (having Frankel grade E with normal bowel bladder control) and 18 patients (64.3%) had good/fair outcome (partial recovery or clinically insignificant recovery) after 3 months. Age, gender and location (axial and sagittal) of benign spinal tumor were not found to have significant variation of neurological outcome. Conclusion: Majority of patients irrespective of the location (axial/sagittal) of the tumor had a favorable clinical outcome three months after the operation. Bang. J Neurosurgery 2024; 13(2): 130-139

Wearables for the Bladder: Stakeholder Perspectives on Moving Multiple Sclerosis Bladder Dysfunction Interventions Into the 21st Century.

Bladder dysfunction (BD) is common in people with multiple sclerosis (MS) and can reduce participation in daily life. Detecting BD early allows for effective prevention-focused treatments such as pelvic floor physical therapy. Pairing neurotechnology with patient-reported outcomes to remotely measure BD could significantly improve monitoring and treatment of BD. Therefore, we describe the process and findings of stakeholder engagement from a human-centered design process to assemble a wearables for the bladder (WeB) kit. Four people with MS with varying BD severity, and 5 MS clinical/research experts had 4 virtual meetings. Commercially available bladder tools were graded for ability to evaluate, monitor, or treat BD. The Health Information Technology Usability Evaluation Scale (utility, usability, feasibility) was used for evaluation. Scoring was performed individually and as a group. Of the 11 devices, 5 obtained mean scores of greater than 6 of 10 for likability, usability, and device utility. The 2 highest scoring (9/10) devices were selected for the pilot. One device measures bladder urine levels, reporting the number/frequency of voids/leaks; the other guides pelvic floor exercises by pairing games on an app with biofeedback from intravaginal sensors. We uncovered critical differences in experts' and patients' appreciation of the tools, and the collaborative engagement led to substantial revisions of initial tool scores. This process underscores the critical role of stakeholder engagement in the selection of digital tools, especially in sensitive domains like pelvic function. Ongoing clinical validation of the selected tools will yield a validated, user-friendly WeB kit that is able to fill gaps in our ability to evaluate BD treatments in people with MS, ultimately reducing the impact of BD on quality of life.

(FOR: Current Bladder Dysfunction Reports) Revisiting Intravesical Dimethyl Sulfoxide

Abstract Purpose of Review Dimethyl Sulfoxide (DMSO) remains an option for the treatment of bladder pain syndrome/interstitial cystitis (BPS/IC) in select patients. This review will discuss the mechanism of action and the role of intravesical DMSO cocktail therapy, as well as outcomes and adverse events for this therapy. Recent Findings Several, but not all historical studies have demonstrated some efficacy for DMSO in the treatment of BPS/IC symptoms including pain and lower urinary tract symptoms such as urgency and frequency. Although DMSO appears superior to placebo, there remain few well-done studies demonstrating support for DMSO use versus other intravesical or alternative BPS/IC treatments. AUA guidelines regarding the role of DMSO have been recently updated. Summary Despite a long history of utilization in the treatment of BPS/IC, the literature supporting its use is not particularly robust. Current AUA guidelines support DMSO as an option in selected patients with a modest level of evidence.

Faster bladder filling in rats reduces detrusor overactivity but worsens (i.e., decreases) bladder compliance.

The impact of bladder filling rate on cystometric outcomes remains unclear. Clinically, faster bladder filling is believed to increase the likelihood of observing detrusor overactivity (DO) in those with bladder dysfunction, although evidence of this is lacking. We executed this study to clarify how changes in bladder filling rate impacted cystometric parameters. Urethane anesthetized female CD rats (n = 19) underwent bladder filling at five different fill rates, a baseline rate scaled to have a filling phase of approximately seven minutes (in line with our previous work), and scaled rates of 1/3x, 2x, 4x, and 8x that speed. Contrary to expectations, filling at faster rates decreased the likelihood of observing detrusor overactivity, with 4x and 8x filling rates demonstrating less detrusor overactivity than the baseline (1x) rate (P = 0.0091 for 4x and P = 0.019 for 8x). However, faster filling rates did decrease bladder compliance. Filling at 4x and 8x demonstrated decreased bladder compliance compared to 1x (P = 0.032 for 4x and P < 0.0001 for 8x). Finally, increasing the filling rate led to increases in bladder capacity at 4x (P = 0.034) and 8x (P = 0.0066) relative to 1x. These results suggest that contrary to expectations, faster filling may not be more effective at eliciting detrusor overactivity (i.e., not a better diagnostic approach). As reductions in detrusor overactivity and increases in bladder capacity are critical parameters for evaluating preclinical therapeutics, faster filling may impair the ability to demonstrate further improvements.

Metformin modulates the TXNIP-NLRP3-GSDMD pathway to improve diabetic bladder dysfunction

To validate the therapeutic efficacy of metformin on diabetic bladder dysfunction (DBD) and further elucidate whether the TXNIP-NLRP3-GSDMD axis serves as a target for metformin in ameliorating DBD. C57BL/6J mice were induced with diet-induced obesity by being fed a high-fat diet (HFD) for 16 weeks. After establishing the model, the mice were treated with metformin for 4 weeks, and their glucose metabolism-related parameters were assessed. Urine spot assays and urodynamic measurements were conducted to reflect the bladder function and urinary behavior in mice, while histological examination was performed to observe morphological changes. Western blot analysis was employed to measure the expression levels of pyroptotic factors such as TXNIP, NLRP3, GSDMD, and tight junction proteins. Metformin treatment significantly improved glucose tolerance and insulin sensitivity in mice. Moreover, it showed promise in decreasing urinary spot occurrence, reducing urination frequency, alleviating non-voiding contractions, and stabilizing peak urinary pressure. Following metformin therapy, mice displayed restored epithelial fold structure, increased thickness of the muscular layer, substantial decrease in muscle fiber content, notably reduced levels of TXNIP and GSDMD proteins in the metformin-treated group compared to the DBD group, and restored expression of tight junction proteins Zo-1, Claudin-1, and Occludin. Metformin ameliorates urothelial cells damage in DBD mice by inhibiting TXNIP generation and reducing NLRP3 and GSDMD production.

Comparison of two modeling approaches for the identification of predictors of complications in children with cerebral palsy following spine surgery

BackgroundChildren with non-ambulatory cerebral palsy (CP) frequently develop progressive neuromuscular scoliosis and require surgical intervention. Due to their comorbidities, they are at high risk for developing peri- and post-operative complications. The objectives of this study were to compare stepwise and LASSO variable selection techniques for consistency in identifying predictors when modelling these post-operative complications and to identify potential predictors of respiratory complications and infections following spine surgery among children with CP.MethodsIn this retrospective cohort study, a large administrative claims database was queried to identify children who met the following criteria: 1) ≤ 25 years old, 2) diagnosis of CP, 3) underwent surgery during the study period, 4) had ≥ 12-months pre-operative, and 5) ≥ 3-months post-operative continuous health plan enrollment. Outcome measures included the development of a post-operative respiratory complication (e.g., pneumonia, aspiration pneumonia, atelectasis, pleural effusion, pneumothorax, pulmonary edema) or an infection (e.g., surgical site infection, urinary tract infection, meningitis, peritonitis, sepsis, or septicemia) within 3 months of surgery. Codes were used to identify CP, surgical procedures, medical comorbidities and the development of post-operative respiratory complications and infections. Two approaches to variable selection, stepwise and LASSO, were compared to determine which potential predictors of respiratory complications and infection development would be identified using each approach.ResultsThe sample included 220 children. During the 3-month follow-up, 21.8% (n = 48) developed a respiratory complication and 12.7% (n = 28) developed an infection. The prevalence of 11 variables including age, sex and 9 comorbidities were initially considered to be potential predictors based on the intended outcome of interest. Model discrimination utilizing LASSO for variable selection was slightly improved over the stepwise regression approach. LASSO resulted in retention of additional comorbidities that may have meaningful associations to consider for future studies, including gastrointestinal issues, bladder dysfunction, epilepsy, anemia and coagulation deficiency.ConclusionsPotential predictors of the development of post-operative complications were identified in this study and while identified predictors were similar using stepwise and LASSO regression approaches, model discrimination was slightly improved with LASSO. Findings will be used to inform future research processes determining which variables to consider for developing risk prediction models.

The relationship between urodynamic bladder compliance and urinary fibrosis markers in children with neurogenic bladder dysfunction

BackgroundDecreased bladder compliance is an important risk factor for upper urinary tract in children with neurogenic bladder dysfunction (NBD). Urodynamics is the gold standard in determining bladder compliance. ObjectiveTo investigate the relationship between low bladder compliance and urinary fibrosis markers in NBD. Study designSpina bifida patients with NBD, who admitted between March 2021 and July 2021 were included. Patients with low compliant bladders, no renal scar, no recurrent urinary tract infections formed low compliance, LC group. Normal compliance, NC group, was comprised of patients with normocompliant bladders and the same characteristics. Control group (Group C) consisted of patients for outpatient surgery and had no known bladder dysfunction. Compliance was calculated with the formula ΔV/ΔP and a value of under 15 ml/cmH2O was accepted as low. Age, gender, urine density, serum urea, creatinine levels and urodynamic parameters were noted. Urinary type 1, type 3 collagen and its precursor procollagen type 3 and serum type 1 and 3 collagen were determined by ELISA. Results72 patients were included (LC group, n:31, NC group, n:24, C group n:17, mean age 7,39±1,24 years). No significant difference was observed in the comparison of age, gender, urine density and serum urea and creatinine values. No significant difference was observed between the LC and NC groups for urodynamic parameters, except for bladder compliance. Urinary collagen type 1 in LC group (11,71±3,02 ng/ml) was found to be significantly higher than that of the C group (9,45±1,97 ng/ml) (p=0,03). Urinary procollagen type 3 was significantly higher in LC group (103,15±24 ng/ml) when compared to C group (82,42±22,26 ng/ml) (p=0,016). Urinary collagen type 1 level above 9,20 ng/ml was 80,6% sensitive and 70,6% specific and urinary procollagen type 3 level above 78 ng/ml was 87% sensitive and 70,6% specific in predicting low compliance. DiscussionThis study seems to be the first study in the literature to evaluate bladder fibrosis and compliance, biochemically, by measuring urinary collagen levels in NBD. Urinary fibrosis markers are not currently an alternative to urodynamics for bladder compliance, but they may have potential to reduce the need for urodynamics with this indication. ConclusionDetermination of urinary collagen levels may be a marker of bladder wall fibrosis and may indirectly show decreased bladder compliance. It is plausible to say that invasive methods such as urodynamics may be less preferred for defining bladder compliance, instead, urinary biomarkers may have merit for this purpose in the future.

Primary vesicoureteral reflux.

Primary vesicoureteral reflux (VUR) is one of the most common urological abnormalities in infants and children. The association of VUR, urinary tract infection (UTI) and renal parenchymal damage is well established. The most serious complications of VUR-associated reflux nephropathy are hypertension and proteinuria with chronic kidney disease. Over the past two decades, our understanding of the natural history of VUR has improved, which has helped to identify patients at increased risk of both VUR and VUR-associated renal injury. The main goals in the treatment of paediatric patients with VUR are the prevention of recurrent UTIs and minimizing the risk of renal scarring and long-term renal impairment. Currently, there are four options for managing primary VUR in infants and children: surveillance or intermittent treatment of UTIs with management of bladder and bowel dysfunction; continuous antibiotic prophylaxis; endoscopic subureteral injection of tissue-augmenting substances; and ureteral reimplantation via open, laparoscopic or robotic-assisted surgery. Current debates regarding key aspects of management include when to perform diagnostic imaging and how to best identify the paediatric patients that will benefit from continuous antibiotic prophylaxis or surgical intervention, including endoscopic injection therapy and minimally invasive ureteral reimplantation. Evolving technologies, such as artificial intelligence, have the potential to assist clinicians in the decision-making process and in the individualization of diagnostic imaging and treatment of infants and children with VUR in the future.