Machine learning models for screening clinically significant nephrolithiasis in overweight and obese populations.

PURPOSES: Our aim is to build and evaluate models to screen for clinically significant nephrolithiasis in overweight and obesity populations using machine learning (ML) methodologies and simple health checkup clinical and urine parameters easily obtained in clinics. METHODS: We developed ML models to screen for clinically significant nephrolithiasis (kidney stone > 2 mm) in overweight and obese populations (body mass index, BMI ≥ 25 kg/m2) using gender, age, BMI, gout, diabetes mellitus, estimated glomerular filtration rate, bacteriuria, urine pH, urine red blood cell counts, and urine specific gravity. The data were collected from hospitals in Kaohsiung, Taiwan between 2012 and 2021. RESULTS: Of the 2928 subjects we enrolled, 1148 (39.21%) had clinically significant nephrolithiasis and 1780 (60.79%) did not. The testing dataset consisted of data collected from 574 subjects, 235 (40.94%) with clinically significant nephrolithiasis and 339 (59.06%) without. One model had a testing area under curve of 0.965 (95% CI, 0.9506-0.9794), a sensitivity of 0.860 (95% CI, 0.8152-0.9040), a specificity of 0.947 (95% CI, 0.9230-0.9708), a positive predictive value of 0.918 (95% CI, 0.8820-0.9544), and negative predictive value of 0.907 (95% CI, 0.8756-0.9371). CONCLUSION: This ML-based model was found able to effectively distinguish the overweight and obese subjects with clinically significant nephrolithiasis from those without. We believe that such a model can serve as an easily accessible and reliable screening tool for nephrolithiasis in overweight and obesity populations and make possible early intervention such as lifestyle modifications and medication for prevention stone complications.

Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Detrusor Hyperactivity with Impaired Contractility via Transient Potential Vanilloid Channels: A Rat Model for Ovarian Hormone Deficiency.

This study explores low-intensity extracorporeal shock wave therapy (LiESWT)'s efficacy in alleviating detrusor hyperactivity with impaired contractility (DHIC) induced by ovarian hormone deficiency (OHD) in ovariectomized rats. The rats were categorized into the following four groups: sham group; OVX group, subjected to bilateral ovariectomy (OVX) for 12 months to induce OHD; OVX + SW4 group, underwent OHD for 12 months followed by 4 weeks of weekly LiESWT; and OVX + SW8 group, underwent OHD for 12 months followed by 8 weeks of weekly LiESWT. Cystometrogram studies and voiding behavior tracing were used to identify the symptoms of DHIC. Muscle strip contractility was evaluated through electrical-field, carbachol, ATP, and KCl stimulations. Western blot and immunofluorescence analyses were performed to assess the expressions of various markers related to bladder dysfunction. The OVX rats exhibited significant bladder deterioration and overactivity, alleviated by LiESWT. LiESWT modified transient receptor potential vanilloid (TRPV) channel expression, regulating calcium concentration and enhancing bladder capacity. It also elevated endoplasmic reticulum (ER) stress proteins, influencing ER-related Ca2+ channels and receptors to modulate detrusor muscle contractility. OHD after 12 months led to neuronal degeneration and reduced TRPV1 and TRPV4 channel activation. LiESWT demonstrated potential in enhancing angiogenic remodeling, neurogenesis, and receptor response, ameliorating DHIC via TRPV channels and cellular signaling in the OHD-induced DHIC rat model.

Skin sympathetic nerve activity as a potential biomarker for overactive bladder.

PURPOSE: Abnormalities in autonomic function are associated with an overactive bladder (OAB). Heart rate variability is generally used as the sole assessment of autonomic activity; however, we utilized neuECG, a novel method of recording skin electrical signals, to assess autonomic nervous function in healthy controls and patients with OAB before and after treatment. METHODS: The prospective sample included 52 participants: 23 patients newly diagnosed with OAB and 29 controls. Autonomic function was assessed in all participants in the morning using neuECG, which analyzed the average skin sympathetic nerve activity (aSKNA) and electrocardiogram simultaneously. All patients with OAB were administered antimuscarinics; urodynamic parameters were assessed before treatments; autonomic and bladder functions using validated questionnaires for OAB symptoms were evaluated before and after OAB treatment. RESULTS: Patients with OAB had significantly higher baseline aSKNA (p = 0.003), lower standard deviation of the normal-to-normal beat intervals, lower root mean square of the successive differences, lower high-frequency, and higher low-frequency than did controls. Baseline aSKNA had the highest value in predicting OAB (AUROC = 0.783, p < 0.001). The aSKNA was negatively correlated with first desire and normal desire in urodynamic studies (both p = 0.025) and was significantly decreased after treatment at rest, stress, and recovery phases, as compared to those before treatment (p = 0.046, 0.017, and 0.017, respectively). CONCLUSION: Sympathetic activity increased significantly in patients with OAB compared to that in healthy controls, and decreased significantly post-treatment. Higher aSKNA is associated with decreased bladder volume at which voiding is desired. SKNA may be a potential biomarker for diagnosing OAB.

The Molecular Mechanism and Therapeutic Application of Autophagy for Urological Disease.

Autophagy is a lysosomal degradation process known as autophagic flux, involving the engulfment of damaged proteins and organelles by double-membrane autophagosomes. It comprises microautophagy, chaperone-mediated autophagy (CMA), and macroautophagy. Macroautophagy consists of three stages: induction, autophagosome formation, and autolysosome formation. Atg8-family proteins are valuable for tracking autophagic structures and have been widely utilized for monitoring autophagy. The conversion of LC3 to its lipidated form, LC3-II, served as an indicator of autophagy. Autophagy is implicated in human pathophysiology, such as neurodegeneration, cancer, and immune disorders. Moreover, autophagy impacts urological diseases, such as interstitial cystitis /bladder pain syndrome (IC/BPS), ketamine-induced ulcerative cystitis (KIC), chemotherapy-induced cystitis (CIC), radiation cystitis (RC), erectile dysfunction (ED), bladder outlet obstruction (BOO), prostate cancer, bladder cancer, renal cancer, testicular cancer, and penile cancer. Autophagy plays a dual role in the management of urologic diseases, and the identification of potential biomarkers associated with autophagy is a crucial step towards a deeper understanding of its role in these diseases. Methods for monitoring autophagy include TEM, Western blot, immunofluorescence, flow cytometry, and genetic tools. Autophagosome and autolysosome structures are discerned via TEM. Western blot, immunofluorescence, northern blot, and RT-PCR assess protein/mRNA levels. Luciferase assay tracks flux; GFP-LC3 transgenic mice aid study. Knockdown methods (miRNA and RNAi) offer insights. This article extensively examines autophagy's molecular mechanism, pharmacological regulation, and therapeutic application involvement in urological diseases.

Effects of Therapeutic Platelet-Rich Plasma on Overactive Bladder via Modulating Hyaluronan Synthesis in Ovariectomized Rat.

Postmenopausal women who have ovary hormone deficiency (OHD) may experience urological dysfunctions, such as overactive bladder (OAB) symptoms. This study used a female Sprague Dawley rat model that underwent bilateral ovariectomy (OVX) to simulate post-menopause in humans. The rats were treated with platelet-rich plasma (PRP) or platelet-poor plasma (PPP) after 12 months of OVX to investigate the therapeutic effects of PRP on OHD-induced OAB. The OVX-treated rats exhibited a decrease in the expression of urothelial barrier-associated proteins, altered hyaluronic acid (hyaluronan; HA) production, and exacerbated bladder pathological damage and interstitial fibrosis through NFƘB/COX-2 signaling pathways, which may contribute to OAB. In contrast, PRP instillation for four weeks regulated the inflammatory fibrotic biosynthesis, promoted cell proliferation and matrix synthesis of stroma, enhanced mucosal regeneration, and improved urothelial mucosa to alleviate OHD-induced bladder hyperactivity. PRP could release growth factors to promote angiogenic potential for bladder repair through laminin/integrin-α6 and VEGF/VEGF receptor signaling pathways in the pathogenesis of OHD-induced OAB. Furthermore, PRP enhanced the expression of HA receptors and hyaluronan synthases (HAS), reduced hyaluronidases (HYALs), modulated the fibroblast-myofibroblast transition, and increased angiogenesis and matrix synthesis via the PI3K/AKT/m-TOR pathway, resulting in bladder remodeling and regeneration.

Therapeutic Effect of Platelet-Rich Plasma Improves Bladder Overactivity in the Pathogenesis of Ketamine-Induced Ulcerative Cystitis in a Rat Model.

The present study attempted to elucidate whether intravesical instillation of platelet-rich plasma (PRP) could decrease bladder inflammation and ameliorate bladder hyperactivity in ketamine ulcerative cystitis (KIC) rat model. Female Sprague Dawley (S-D) rats were randomly divided into control group, ketamine-treated group, ketamine with PRP treated group, and ketamine with platelet-poor plasma (PPP) treated group. Cystometry and micturition frequency/volume studies were performed to investigate bladder function. The morphological change of bladder was investigated by Mason's trichrome staining. Western blotting analysis were carried out to examine the protein expressions of inflammation, urothelial differentiation, proliferation, urothelial barrier function, angiogenesis and neurogenesis related proteins. The results revealed that treatment with ketamine significantly deteriorated bladder capacity, decreased voiding function and enhanced bladder overactivity. These pathological damage and interstitial fibrosis may via NF-κB/COX-2 signaling pathways and muscarinic receptor overexpression. PRP treatment decreased inflammatory fibrotic biosynthesis, attenuated oxidative stress, promoted urothelial cell regeneration, and enhanced angiogenesis and neurogenesis, thereafter recovered bladder dysfunction and ameliorate the bladder hyperactivity in KIC rat model. These findings suggested that the PRP therapy may offer new treatment options for those clinical KIC patients.

The impact of urine microbiota in patients with lower urinary tract symptoms.

INTRODUCTION: Inflammation and infection are causative factors of benign prostatic hyperplasia (BPH). Urine is not sterile, and urine microbiota identified by DNA sequencing can play an important role in the development of BPH and can influence the severity of lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: We collected mid-stream voided urine samples from BPH patients and control participants and stored them in a freezer at - 80 °C. All enrolled participants were requested to provide information about their clinical characteristics and complete the International Prostate Symptom Score (IPSS) questionnaire. Each step of the procedure, including the extraction of the genomic DNA from the urine samples; the amplification by polymerase chain reaction (PCR); PCR product quantification, mixing, and purification; DNA library preparation; and sequencing was performed with quality control (QC) measures. Alpha diversity was indicative of the species complexity within individual urine samples, and beta diversity analysis was used to evaluate the differences among the samples in terms of species complexity. Pearson's correlation analysis was performed to calculate the relationship between the clinical characteristics of the participants and the microbiota species in the urine samples. RESULTS: We enrolled 77 BPH patients and 30 control participants who reported no recent antibiotic usage. Old age, high IPSS and poor quality of life were observed in the participants of the BPH group. No significant differences were observed in the alpha diversity of the samples. In the beta diversity analysis, there was a significant difference between the microbiota in the samples of the BPH and control groups according to ANOSIM statistical analysis. On comparing the groups, the ten bacterial genera present in the samples of the BPH group in descending order of abundance were: Sphingomonas, Bacteroides, Lactobacillus, Streptococcus, Alcaligenes, Prevotella, Ruminococcaceae UCG-014, Escherichia_Shigella, Akkermansia, and Parabacteroides. Spearman's correlation analysis revealed that urine samples showing the presence of the bacterial genera Haemophilus, Staphylococcus, Dolosigranulum, Listeria, Phascolarctobacterium, Enhydrobacter, Bacillus, [Ruminococcus]torques, Faecalibacterium, and Finegoldia correlated with a high IPSS, and severe storage and voiding symptoms (P < 0.05). CONCLUSION: Our current study shows that dysbiosis of urine microbiota may be related to the development of BPH and the severity of LUTS. Further research targeting specific microbes to identify their role in the development of diseases is necessary and might provide novel diagnostic biomarkers and therapeutic options.

Therapeutic effect of Low intensity Extracorporeal Shock Wave Therapy (Li-ESWT) on diabetic bladder dysfunction in a rat model.

Objectives: Low intensity extracorporeal shock wave therapy (Li-ESWT) has proven to be effective and safe for the treatment of various urological disorders including erectile dysfunction and chronic pelvic pain syndrome. In this study, we elucidated the therapeutic effect and possible mechanisms of Li-ESWT on diabetic bladder dysfunction (DBD) in a rat model. Materials and Methods: In all, thirty-two female Sprague-Dawley rats were divided into three groups: normal control (NC), diabetes mellitus (DM) control, and DM Li-ESWT. The two DM groups were given high fat diets for one month, followed by 2 intraperitoneal injections of streptozotocin (STZ) 30 mg/kg separated by one week. Body weight and fasting blood glucose were monitored every week. Only rats with fasting blood glucose 140 mg/dL or more were considered diabetic and used in the subsequent portions of the study. The Li-ESWTs were applied toward the pelvis of the rats twice a week for 4 weeks with energy flux density (EFD) 0.02 mJ/mm2, 500 shocks, at 3Hz. All rats underwent plasma insulin tolerance test, conscious cystometry, leak-point pressure (LPP) assessment, and immunohistochemical studies. Results: DM groups had significantly lower insulin sensitivity and higher body weight. Conscious cystometry also revealed voiding dysfunctions. In the DM Li-ESWT group, the rats had significantly improved voiding functions that were reflected in longer micturition intervals and higher LPP compared to DM control. Immunofluorescence in DM control groups showed increased tyrosine hydroxylase (TH) expression and decreased neuronal nitric oxide synthase (nNOS) expression in the longitudinal urethral smooth muscles. Besides, rats had dilations and deformities of suburothelium capillary network of the bladder, revealing the deterioration of the nerve function of the urethra and destruction of the vascularization of the bladder. However, the DM Li-ESWT group exhibited recovery of the nerve expression of the urethra and vascularization of bladder. Conclusions: Li-ESWT ameliorates the bladder dysfunction and urinary continence in the DBD rat model, reflected in restoration of the nerve expression of the urethra and the vascularization of the bladder. Non-invasive Li-ESWT could be an alternative therapeutic option for DBD.

The metabolic syndrome is associated with the risk of urothelial carcinoma from a health examination database.

PURPOSE: The metabolic syndrome was associated with bladder cancer in the previous studies. However, there have no large-scale cohort studies to elucidate the relationship between metabolic syndromes and urothelial carcinoma including urinary bladder urothelial carcinoma (UBUC) and upper tract urothelial carcinoma (UTUC). METHODS: We analyze a population-based cohort study by using physical examination data and diagnosis of UC from the Taiwan Cancer Registry Database. Differences in demographic and clinical characteristics among UTUC and non-UTUC groups, UBUC and non-UBUC groups were compared. Odds ratios (ORs) for determining risk factors were estimated through the multiple logistic regression model. RESULTS: A total of 557,063 records for 211,319 participants which consisted of 31 UTUC and 309 UBUC met the eligibility criteria in this study. Our results showed that female are more likely to develop UTUC than male. As opposed to UTUC, male are more likely to develop UBUC than female. It also showed that participants smoked or chewed betel quid daily are more likely to develop UBUC. Age and estimated glomerular filtration rate (eGFR) are significantly increased the risk of developing UTUC. The association between the eGFR and risk of UTUC is stronger (P < 0.001) for eGFR < 45 (vs. eGFR ≥ 75, OR = 6.795; 95% CI 2.901-15.917). Metabolic syndrome is related to higher risk of UBUC incidence [OR was 1.373 (95% CI 1.104-1.707)]. CONCLUSIONS: There was a significant relationship between the incidence of UBUC and metabolic syndrome. Renal function impairment presents higher risk in both UBUC and UTUC development.

Bladder Hyperactivity Induced by Oxidative Stress and Bladder Ischemia: A Review of Treatment Strategies with Antioxidants.

Overactive bladder (OAB) syndrome, including frequency, urgency, nocturia and urgency incontinence, has a significantly negative impact on the quality-of-life scale (QoL) and can cause sufferer withdrawal from social activities. The occurrence of OAB can result from an imbalance between the production of pro-oxidants, such as free radicals and reactive species, and their elimination through protective mechanisms of antioxidant-induced oxidative stress. Several animal models, such as bladder ischemia/reperfusion (I/R), partial bladder outlet obstruction (PBOO) and ovarian hormone deficiency (OHD), have suggested that cyclic I/R during the micturition cycle induces oxidative stress, leading to bladder denervation, bladder afferent pathway sensitization and overexpression of bladder-damaging molecules, and finally resulting in bladder hyperactivity. Based on the results of previous animal experiments, the present review specifically focuses on four issues: (1) oxidative stress and antioxidant defense system; (2) oxidative stress in OAB and biomarkers of OAB; (3) OAB animal model; (4) potential nature/plant antioxidant treatment strategies for urinary dysfunction with OAB. Moreover, we organized the relationships between urinary dysfunction and oxidative stress biomarkers in urine, blood and bladder tissue. Reviewed information also revealed the summary of research findings for the effects of various antioxidants for treatment strategies for OAB.

Low-Intensity Extracorporeal Shock Wave Therapy Promotes Bladder Regeneration and Improves Overactive Bladder Induced by Ovarian Hormone Deficiency from Rat Animal Model to Human Clinical Trial.

Postmenopausal women with ovary hormone deficiency (OHD) are subject to overactive bladder (OAB) symptoms. The present study attempted to elucidate whether low-intensity extracorporeal shock wave therapy (LiESWT) alters bladder angiogenesis, decreases inflammatory response, and ameliorates bladder hyperactivity to influence bladder function in OHD-induced OAB in human clinical trial and rat model. The ovariectomized (OVX) for 12 months Sprague-Dawley rat model mimicking the physiological condition of menopause was utilized to induce OAB and assess the potential therapeutic mechanism of LiESWT (0.12 mJ/mm2, 300 pulses, and 3 pulses/second). The randomized, single-blinded clinical trial was enrolled 58 participants to investigate the therapeutic efficacy of LiESWT (0.25 mJ/mm2, 3000 pulses, 3 pulses/second) on postmenopausal women with OAB. The results revealed that 8 weeks' LiESWT inhibited interstitial fibrosis, promoted cell proliferation, enhanced angiogenesis protein expression, and elevated the protein phosphorylation of ErK1/2, P38, and Akt, leading to decreased urinary frequency, nocturia, urgency, urgency incontinence, and post-voided residual urine volume, but increased voided urine volume and the maximal flow rate of postmenopausal participants. In conclusion, LiESWT attenuated inflammatory responses, increased angiogenesis, and promoted proliferation and differentiation, thereby improved OAB symptoms, thereafter promoting social activity and the quality of life of postmenopausal participants.

Low Intensity Extracorporeal Shock Wave Therapy as a Novel Treatment for Stress Urinary Incontinence: A Randomized-Controlled Clinical Study.

Background and Objectives: To evaluate the effects of low intensity extracorporeal shock wave therapy (LiESWT) on stress urinary incontinence (SUI). Materials and Methods: This investigation was a multicenter, single-blind, randomized-controlled trial study. Sixty female SUI patients were randomly assigned to receive LiESWT with 0.25 mJ/mm2 intensity, 3000 pulses, and 3 pulses/s, once weekly for a 4-week (W4) and 8-week (W8) period, or an identical sham LiESWT treatment without energy transmission. The primary endpoint was the changes in urine leakage as measured by a pad test and validated standardized questionnaires, while the secondary endpoint was the changes in a 3-day urinary diary among the baseline (W0), the W4 and W8 of LiESWT, and 1-month (F1), 3-month (F3), and 6-month (F6) follow-up after LiESWT. Results: The results showed that 4 weeks of LiESWT could significantly decrease urine leakage based on the pad test and validated standardized questionnaire scores, as compared to the sham group. Moreover, 8 weeks of LiESWT could significantly reduce urine leakage but increase urine volume and attenuate urgency symptoms, which showed meaningful and persistent improvement at W8, F1, F3, and F6. Furthermore, validated standardized questionnaire scores were significantly improved at W8, F1, F3, and F6 as compared to the baseline (W0). Conclusions: Eight weeks of LiESWT attenuated SUI symptoms upon physical activity, reduced urine leakage, and ameliorated overactive bladder symptoms, which implied that LiESWT significantly improved the quality of life. Our findings suggested that LiESWT could serve as a potentially novel and non-invasive treatment for SUI.

5α-reductase inhibitors impact prognosis of urothelial carcinoma.

BACKGROUND: 5α-reductase inhibitors (5-ARIs) inhibit the pathway of converting the testosterone to dihydrotestosterone and are widely used in benign prostatic hyperplasia patients. Since androgen receptor activation may play a role in urothelial tumorigenesis, we conducted this retrospective cohort study to determine whether 5α-reductase inhibitors (5-ARIs) administration is associated with bladder cancer mortality, bladder cancer recurrence and upper tract urothelial carcinoma mortality, using the Taiwan National Health Insurance database. METHODS: The data of this retrospective cohort study were sourced from the Longitudinal Health Insurance Database of Taiwan, compiled by the Taiwan National Health Insurance database from 1996 to 2010. It consists of 18,530 men with bladder cancer, of whom 474 were 5-ARIs recipients and 4384 men with upper tract urothelial carcinoma, of whom 109 were 5-ARIs recipients. Propensity Score Matching on the age and geographic data was done at the ratio of 1:10. We analyzed the odds ratios (OR) and 95% confidence interval (CI) of the risk of bladder cancer death, bladder cancer recurrence rate and upper tract urothelial carcinoma related death by the 5-ARIs administration. RESULTS: Those who received 5-ARIs showed a lower risk of bladder cancer related death compared to nonusers in multivariable adjusted analysis (OR 0.835, 95% CI 0.71-0.98). However, there was no significant difference in the bladder cancer recurrence rate (OR 0.956, 95% CI 0.82-1.11) and upper tract urothelial carcinoma related mortality in multivariable adjusted analysis (OR 0.814, 95% CI 0.6-1.1). CONCLUSIONS: Patients who receive 5-ARIs have lower bladder cancer related mortality compared to those who don't. 5-ARIs may prove to be a viable strategy to improve bladder cancer outcomes.

Urolithiasis increases the risk of subsequent onset of osteoporosis.

Urolithiasis and osteoporosis are two different pathological entities, but are both important public health issues in older patients. Moreover, the two diseases may share some similar pathogenesis pathway. Currently, few studies focus on the relationship between urolithiasis and osteoporosis. Furthermore, whether the common mobilities influence the long-term osteoporosis rate in urolithiasis patients has never been studied. In the present study, we used the Taiwan National Health Insurance Database (LHID 2000) compiled by the NHI from 1996 to 2013 to determine whether urolithiasis influenced long-term osteoporosis; controls were matched for age, sex, and other comorbidities (including hypertension, diabetes mellitus, dyslipidemia, liver disease, and cardiovascular disease). We included a total of 91,254 patients, including 22,575 patients with urolithiasis and 68,679 control patients. There was a significant difference between the incidence of osteoporosis between the urolithiasis and control groups (adjusted hazard ratio 1.34, 95% CI 1.19-1.79, p < 0.001) during the follow up. The incidence rate of osteoporosis during the follow-up period was 8.87 per 1000 person-years in the urolithiasis group and 6.37 per 1000 person-years in the control group. Based on our results, it is evident that urolithiasis significantly increases the subsequent osteoporosis rate. Though the clinical mechanisms are not fully understood, patients who have a history of urolithiasis may need regular follow-up assessment of bone marrow density.

The 12-month follow-up of the low-intensity extracorporeal shockwave therapy in the treatment of patients with chronic pelvic pain syndrome refractory to 3-As medications.

PURPOSE: Applying low-intensity extracorporeal shockwave therapy (LI-ESWT) has been reported to improve symptoms of refractory chronic pelvic pain syndrome (CPPS) in short-term follow-up. This study aims to demonstrate the effect of LI-ESWT on refractory CPPS over the span of a 12-month follow-up. MATERIALS AND METHODS: This was an open-label, single-arm prospective study. LI-ESWT consisted of 3000 shock waves once weekly for 4 weeks (Duolith SD1 T-Top) were applied. Clinical symptoms were re-assessed at 1, 3, 6, and 12 months using NIH-CPSI score, visual analog scale, 5-item version of the International Index of Erectile Function and International Prostate Symptom Score. RESULTS: Thirty-one of the 43 patients enrolled had a successful response at the 1-month follow up after the treatment. Twenty-six of the 31 patients who responded successfully to LI-ESWT at the 1-month follow-up, maintained their response at the 6- and 12-month follow-up. The existence of psychosocial disorder at the baseline characteristics analysis was the only potential factor that may hinder the effectiveness of LI-ESWT. CONCLUSIONS: LI-ESWT has shown to be a safe and effective therapy for CPPS patients at the long-term follow-up. History of psychological disorders might be a significant predictor of a successful response.

Effect of preoperative computed tomography parameters and obesity on surgical outcomes of laparoendoscopic single-site adrenalectomy.

BACKGROUND: The aims of the present study were to (1) analyse preoperative computed tomography (CT) parameters, (2) investigate whether obesity and CT parameters affect surgical outcomes in patients undergoing LESS lateral retroperitoneal adrenalectomy, and (3) further establish the optimal cutoff point of CT parameters for tolerable operating time. METHODS: Between January 2010 and August 2016, patients who underwent LESS adrenalectomy through the retroperitoneal approach in our hospitals were included. Patients' demographic data, preoperatively measured CT parameters (the depth and horizontal width to the adrenal gland in the axial view of abdominal CT, the vertical height in the coronal view of CT, and the angle of the depth and horizontal width), and intraoperative (operative time and blood loss) and postoperative (hospital stay and complications) parameters were retrospectively reviewed. Linear regression was performed to determine factors that potentially affect surgical outcomes. RESULTS: In 116 patients, depth was the only CT parameter associated with surgical outcomes. Large depth (P = 0.005; 95% CI 1.739-9.256) and high BMI (P = 0.012; 95% CI 0.357-2.851) were factors significantly associated with longer operative time. The area under the ROC curve for the depth was 0.69 (P = 0.002), and the cutoff point 10.48 cm may be the tolerable operating time. CONCLUSIONS: Our results suggest a depth limit of 10.48 cm for the optimal prediction of operating time less than 90 min; although obese patients and deeper adrenal glands had longer operative time, LESS adrenalectomy could be performed in the obese patients without increased blood loss, prolonged hospital stay, or increased pain.

How to optimise urinary continence in anatomical endoscopic enucleation of the prostate?

The traditional transurethral resection of the prostate (TURP) is considered as gold-standard surgical treatment to relieve symptoms resulting from bladder outlet obstruction by prostate enlargement. However, with the advances of novel laser technologies and more experienced surgeon conquering the steep learning curve, anatomical endoscopic enucleation of prostate (AEEP) has become a more popular alternative surgical technique. Although AEEP has compatible functional outcome, less blood loss, shorter catheterisation duration and hospital stay, the risk of post-operative urinary incontinence (UI) is often an issue of concern. In this review, we focus on discussion about risk factors related to increased incidence of UI, some surgical tips to avoid damaging external urinary sphincter and treatment strategies to facilitate recovery of urinary continence after surgery.

Elucidating Mechanisms of Bladder Repair after Hyaluronan Instillation in Ketamine-Induced Ulcerative Cystitis in Animal Model.

Ketamine-induced ulcerative cystitis (KIC) initially damaged the bladder mucosa and induced contracted bladder thereafter. Hyaluronan (hyaluronic acid; HA) instillation to the bladder has been used to treat KIC. The present study investigated bladder injury by urothelial defect and HA degeneration and bladder repair by urothelium proliferation and differentiation. This work was based on the hypothesis that HA treatment altered the bladder urothelial layer and the expression of hyaluronan-metabolizing enzymes and/or HA receptors in KIC. Cystometrogram study and tracing analysis of voiding behavior revealed that the ketamine-treated rats exhibited significant bladder hyperactivity with an increase in micturition frequency and a decrease in bladder capacity. The expression of inflammatory and fibrosis markers was also increased in the ketamine-treated group. Moreover, ketamine administration decreased the expression of urothelial barrier-associated protein, altered HA production, and induced abnormal urothelial differentiation, which might attribute to urothelial lining defects. However, HA instillation ameliorated bladder hyperactivity, lessened bladder mucosa damage, and decreased interstitial fibrosis. HA instillation also improved the level of HA receptors (CD44, Toll-like receptor-4, and receptor for HA-mediated motility) and HA synthases 1 to 3 and decreased the expression of hyaluronidases in the urothelial layer of bladder, resulting in enhanced mucosal regeneration. These findings suggested that HA could modulate inflammatory responses, enhance mucosal regeneration, and improve urothelial lining defects in KIC.

Mirabegron is alternative to antimuscarinic agents for overactive bladder without higher risk in hypertension: a systematic review and meta-analysis.

PURPOSE: Mirabegron, a ß3-adrenoceptor agonist, was approved for overactive bladder (OAB), but worsened hypertension was a potential risk based on its mechanism of action. Besides, head to head comparisons were limited between mirabegron and antimuscarinic agents, the prior first-line pharmacotherapy of OAB. In this regard, we performed a systematic review and meta-analysis to compare their efficacy as well as safety, especially in blood pressure changes. MATERIALS AND METHODS: Literature search was conducted in PubMed, Medline and seven randomized clinical trial (RCT) register databases of WHO, EU, USA, Taiwan, China, Japan and Cochrane. Completed RCTs for OAB with mirabegron and antimuscarinics were identified and the last comprehensive search was run in August 2017. Cochrane risk of bias tool was used to assess the potential bias, and RevMan5 software was performed for meta-analysis. RESULTS: Seven eligible RCTs (four for mirabegron vs. tolterodine and three for mirabegron vs. solifenacin) were included and demonstrated similar efficacy in micturitions, incontinence, and nocturia between mirabegron and antimuscarinics. In hypertension issue, no statistical differences were showed in risk ratio (RR) of hypertension events, change of blood pressure from baseline and change of blood pressure from placebo for all participants. On the other hand, RR of dry mouth was significantly lower in mirabegron users. CONCLUSIONS: Mirabegron was not inferior effective in improving OAB symptoms compared with antimuscarinic agents. In addition, mirabegron presented lower incidence of dry mouth and not higher risk for hypertension. Therefore, mirabegron has potential to be an alternative therapeutic option for OAB control.

Associations of VEGF Gene Polymorphisms With Erectile Dysfunction and Related Risk Factors.

BACKGROUND: Repeated evidence from animal models suggests a strong link between vascular endothelial growth factor (VGEF) and penile vasculature and erectile function because VEGF can alter the physiologic pathways involved in the regulation of penile vasomotor tone. AIM: To investigate three VEGF polymorphisms and their link to erectile dysfunction (ED). METHODS: We enrolled 688 Taiwanese men with a mean age of 55.6 years (SD = 4.5) during a free health screening. All participants provided complete medical histories and underwent physical examinations. Fasting blood samples were obtained for biochemical analysis and hormone profiling. The allelic discrimination of three VEGF gene polymorphisms (460T/C [rs833061], 1154G/A [rs1570360], and 2578A/C [rs699947]) was performed using validated TaqMan single-nucleotide polymorphism genotyping assays. OUTCOMES: Subjects underwent assessment using the simplified five-item International Index of Erectile Function to diagnose and assess ED severity. RESULTS: The results showed that diabetes mellitus (odds ratio [OR] = 3.27, P < .01), hypertension (OR = 3.47, P < .01), and having the VEGF 2578A allele (OR = 1.54, P = .01) were the three most independent risk factors for ED. In univariate analysis, all three VEGF polymorphisms (460C, 1154A, and 2578A) were significantly associated with a higher prevalence of coronary artery disease (P < .01) and greater frequencies of hypertension were found in carriers of the 1154A allele and the 2578A allele (P = .01). Multiple logistic regression analysis showed a significant association between VEGF 2578A allele carrier status and ED (OR = 1.54, 95% CI = 1.10∼2.15, P = .01). Furthermore, the prevalence and severity of ED were significantly increased with an increment of the 2578A allele number (P < .05). CLINICAL IMPLICATIONS: VEGF 2578C/A gene polymorphisms could be a genetic susceptibility factor for the development of ED. STRENGTH AND LIMITATION: This is the first study to investigate the genetic susceptibility of VEGF polymorphisms to ED. This study was cross-sectional with a lack of functional and molecular production investigations. Data on the association among conditions might not allow definitive conclusions about causal links. CONCLUSION: This study showed that VEGF 2578A allele carriers in a Taiwanese population are at greater risk for ED. Lee Y-C, Huang S-P, Tsai C-C, et al. Associations of VEGF Gene Polymorphisms With Erectile Dysfunction and Related Risk Factors. J Sex Med 2017;14:510-517.