Management of Male Infertility with Coexisting Sexual Dysfunction: A Consensus Statement and Clinical Recommendations from the Asia-Pacific Society of Sexual Medicine (APSSM) and the Asian Society of Men's Health and Aging (ASMHA).

Male infertility (MI) and male sexual dysfunction (MSD) can often coexist together due to various interplay factors such as psychosexual, sociocultural and relationship dynamics. The presence of each form of MSD can adversely impact male reproduction and treatment strategies will need to be individualized based on patients' factors, local expertise, and geographical socioeconomic status. The Asia Pacific Society of Sexual Medicine (APSSM) and the Asian Society of Men's Health and Aging (ASMHA) aim to provide a consensus statement and practical set of clinical recommendations based on current evidence to guide clinicians in the management of MI and MSD within the Asia-Pacific (AP) region. A comprehensive, narrative review of the literature was performed to identify the various forms of MSD and their association with MI. MEDLINE and EMBASE databases were searched for the following English language articles under the following terms: "low libido", "erectile dysfunction", "ejaculatory dysfunction", "premature ejaculation", "retrograde ejaculation", "delayed ejaculation", "anejaculation", and "orgasmic dysfunction" between January 2001 to June 2022 with emphasis on published guidelines endorsed by various organizations. This APSSM consensus committee panel evaluated and provided evidence-based recommendations on MI and clinically relevant MSD areas using a modified Delphi method by the panel and specific emphasis on locoregional socio-economic-cultural issues relevant to the AP region. While variations exist in treatment strategies for managing MI and MSD due to geographical expertise, locoregional resources, and sociocultural factors, the panel agreed that comprehensive fertility evaluation with a multidisciplinary management approach to each MSD domain is recommended. It is important to address individual MI issues with an emphasis on improving spermatogenesis and facilitating reproductive avenues while at the same time, managing various MSD conditions with evidence-based treatments. All therapeutic options should be discussed and implemented based on the patient's individual needs, beliefs and preferences while incorporating locoregional expertise and available resources.

Clinical recommendations on penile reconstructive and prosthetic surgery: a consensus statement from the Asia-Pacific Society of Sexual Medicine.

Introduction: Penile reconstructive and prosthetic surgery remains a highly specialized field where potential complications can be devastating, and unrealistic patient expectations can often be difficult to manage. Furthermore, surgical practice can vary depending on locoregional expertise and sociocultural factors. Methods: The Asia Pacific Society of Sexual Medicine (APSSM) panel of experts reviewed contemporary evidence regarding penile reconstructive and prosthetic surgery with an emphasis on key issues relevant to the Asia-Pacific (AP) region and developed a consensus statement and set of clinical practice recommendations on behalf of the APSSM. The Medline and EMBASE databases were searched using the following terms: "penile prosthesis implant," "Peyronie's disease," "penile lengthening," "penile augmentation," "penile enlargement," "buried penis," "penile disorders," "penile trauma," "transgender," and "penile reconstruction" between January 2001 and June 2022. A modified Delphi method was undertaken, and the panel evaluated, agreed, and provided consensus statements on clinically relevant penile reconstructive and prosthetic surgery, namely (1) penile prosthesis implantation, (2) Peyronie's disease, (3) penile trauma, (4) gender-affirming (phalloplasty) surgery, and (5) penile esthetic (length and/or girth enlargement) surgery. Main outcome measures: Outcomes were specific statements and clinical recommendations according to the Oxford Centre for Evidence-Based Medicine, and if clinical evidence is lacking, a consensus agreement is adopted. The panel provided statements on clinical aspects of surgical management in penile reconstructive and prosthetic surgery. Results: There is a variation in surgical algorithms in patients based on sociocultural characteristics and the availability of local resources. Performing preoperative counseling and obtaining adequate informed consent are paramount and should be conducted to discuss various treatment options, including the pros and cons of each surgical intervention. Patients should be provided with information regarding potential complications related to surgery, and strict adherence to safe surgical principles, preoperative optimization of medical comorbidities and stringent postoperative care are important to improve patient satisfaction rates. For complex patients, surgical intervention should ideally be referred and performed by expert high-volume surgeons to maximize clinical outcomes. Clinical implications: Due to the uneven distribution of surgical access and expertise across the AP region, development of relevant comprehensive surgical protocols and regular training programs is desirable. Strengths and Limitations: This consensus statement covers comprehensive penile reconstructive and prosthetic surgery topics and is endorsed by the APSSM. The variations in surgical algorithms and lack of sufficient high-level evidence in these areas could be stated as a limitation. Conclusion: This APSSM consensus statement provides clinical recommendations on the surgical management of various penile reconstructive and prosthetic surgeries. The APSSM advocates for surgeons in AP to individualize surgical options based on patient condition(s) and needs, surgeon expertise, and local resources.

Consensus of Experts on the Treatment of Sexual Dysfunction after Surgery for Prostate Cancer in Taiwan.

According to the Taiwan Cancer Report, in 2018, prostate cancer was one of the top five cancers reported in men. Each year, many patients with prostate cancer undergo radical prostatectomy (RP) therapy. One of the most common RP complications is erectile dysfunction (ED). Although consensus guidelines for the management of sexual dysfunction after prostate cancer surgery have been developed for many Western and Asian countries, no such clinical practice guidelines have been developed for Taiwan. The consensus opinions expressed in this article were discussed by numerous experienced physicians in Taiwan, based on both existing international guidelines and their individual experiences with clinical trials and providing advice to clinical physicians on how to inform patients of the risk of ED prior to surgery. This review also discusses how recovery and rehabilitation may be affected by socioeconomic status, the existence of an intimate relationship, comorbidities, or the need for cancer adjuvant therapy and how to determine rehabilitation goals and provide appropriate treatments to assist in the recovery of both short- and long-term sexual function.

Prevalence of Lower Urinary Tract Symptoms in Children with Attention-Deficit/Hyperactivity Disorder: Comparison of Hospital and Population-Based Cohorts of 13,000 Patients.

Background: This study investigates the prevalence of lower urinary tract symptoms (LUTS) in school-age children with Attention-Deficit/Hyperactivity Disorder (ADHD) based on hospital-based and population-based cohorts. Methods: The hospital-based sample comprised 42 children with ADHD and 65 without ADHD aged 6−12 years. Voiding dysfunction was assessed by the Dysfunctional Voiding Scoring System (DVSS) questionnaire. We compared the baseline data, DVSS score, and uroflowmetry between the two groups. For the population-based cohort in the national insurance database, we included 6526 children aged 6−12 years, whose claims record included the diagnosis of ADHD, and another 6526 control subjects matched by gender and age. We compared the presence of LUTS diagnosis codes between the two groups. Results: Our results showed that, for the hospital-based cohort, the mean total DVSS score and the proportion of significant LUTS in children in the ADHD group were significantly higher than in subjects in the non-ADHD group. The DVSS subscales showed that the item "I cannot wait when I have to pee" item was significantly higher in the ADHD group (1.62 ± 1.17 vs. 0.90 ± 1.09, p = 0.002). For the population-based cohort, children with ADHD had a significantly higher likelihood of storage symptoms (5.53% vs. 2.91%, p < 0.001) and enuresis (3.28% vs. 1.95%, p < 0.001) compared with those of the no ADHD group. Conclusions: Children with ADHD have a higher prevalence of significant LUTS, especially storage symptoms and enuresis, than children without ADHD. The observed correlations between ADHD and LUTS provided the supporting evidence to evaluate the concomitant voiding dysfunction in children with ADHD.

The flow index provides a comprehensive assessment of erectile dysfunction by combining blood flow velocity and vascular diameter.

Dynamic duplex sonography (DUS) is not comprehensive in the evaluation of arteriogenic erectile dysfunction (ED). We introduced a new parameter, the flow index (FI), into the assessment of arteriogenic ED. A retrospective review of a prospective database was conducted. Patients undergoing DUS and pelvic computed tomography angiography for the evaluation of ED were included. The FI was calculated from peak systolic velocity (PSV) and the percentages of pelvic arterial (PLA) stenosis. Correlations between PSV, PLA stenosis, the FI, and erectile function were calculated. Eighty-three patients were included. Compared with PSV, the FI had better correlations with the erection hardness score (EHS) (rs = 0.405, P < 0.001 for FI; rs = 0.294, P = 0.007 for PSV). For EHS < 3, the areas under the ROC curve of FI and PSV were 0.759 and 0.700, respectively. In patients with normal DUS but EHS < 3, PLA stenosis was more severe (62.5% vs. 10.0%, P = 0.015), and the FI was lower (8.35 vs. 57.78, P = 0.006), while PSV was not different. The FI is better than PSV in the evaluation of arteriogenic ED. On the other hand, assessment of the pelvic arterial system should be included in the evaluation of ED.

Clinical Implications of Nadir Serum Prostate-Specific Antigen Levels After Transurethral Enucleation of the Prostate.

Objective: Prostate-specific antigen levels after transurethral enucleation of the prostate may serve as indicators of residual cancer foci. The objective of this study was to investigate the association between the post-transurethral enucleation of the prostate nadir prostate-specific antigen level and prostate cancer. Materials and Methods: We retrospectively reviewed the data of 428 men who underwent transurethral enucleation of the prostate between March 2015 and April 2021. Based on the following exclusion criteria, we excluded 106 men from our analysis: men with metastatic prostate cancer, incomplete transurethral enucleation of the prostate, and missing prostate-specific antigen or prostate size data. Three hundred and twenty-two patients were finally enrolled in our study. These patients were classified into four groups according to the surgical pathology: benign, transition zone (cancer only in the adenoma or transition zone), peripheral zone, and transition and peripheral zones. The optimal cutoff post-transurethral enucleation of the prostate nadir prostate-specific antigen level that predicted residual prostate cancer was determined using receiver operating characteristic curve analysis. Results: In total, 71 (22.0%) men exhibited prostate cancer (median follow-up, 38.0 months). The benign and combined cancer groups showed similar adenoma removal rates (103.0% and 106.7%, respectively). The median nadir prostate-specific antigen levels after transurethral enucleation of the prostate were 0.76, 0.63, 1.79, and 1.70 ng/ml in the benign, transition zone, peripheral zone, and transition and peripheral zone groups, respectively (p < 0.001), with no difference between the benign and transition zone groups (p = 0.458); this suggested that complete transurethral enucleation of the prostate removed all cancer nests in the adenoma in the transition zone group. Receiver operating characteristic curve analysis showed that nadir prostate-specific antigen ≧1.7 ng/ml predicted residual cancer (area under the curve: 0.787) or cancer with a Gleason score of ≧7 (area under the curve: 0.816) in the remaining prostate. Limitations include the retrospective design and the perioperative peripheral zone biopsy rate. Conclusions: The post-transurethral enucleation of the prostate nadir prostate-specific antigen ≧1.7 ng/ml after complete transurethral enucleation of the prostate can predict significant residual cancer. Prostate cancer patients with low post-transurethral enucleation of the prostate prostate-specific antigen levels can be conservatively managed.

A case report of right cardiac ventricle perforation by uncontrolled embolization coil inserted for treating penile veno-occlusive dysfunction.

Coil embolization (CE) is believed effective-safe for treating penile veno-occlusive dysfunction (VOD). From 2012 to 2016, refractory impotence prompted four men to seek further treatment, although they underwent six CEs elsewhere. Uncontrolled coils scattered along penile drainage veins including the deep dorsal veins (n = 3), periprostatic plexus (n = 1), iliac vein (n = 1), right pulmonary artery (n = 2), left pulmonary artery (n = 1), and right ventricle (n = 1). The last one occurred in a 40-year-old house builder, and the coil perforated the right ventricle wall and diaphragm 18 months later. Given no sustainable improvement, CE's safety and efficacy are unreliable for treating patients with VOD.

Ceiling effect of clomiphene citrate on the testosterone to estradiol ratio in eugonadal infertile men.

INTRODUCTION: The testosterone to estradiol ratio (T/E2 ratio) reportedly exerts a stronger effect on semen quality and sexual desire than does testosterone alone. Clomiphene citrate is a selective estrogen receptor modulator that has long been used as an empirical treatment option in the management of idiopathic oligozoospermia. Clomiphene may change the hypothalamus-pituitary-gonad axis and result in the alteration of the T/E2 ratio. No reliable data are available regarding the change in the T/E2 ratio after clomiphene use in eugonadism. METHODS: This study included 24 male patients who were diagnosed with idiopathic infertility with eugonadism. They all received clomiphene citrate (25 mg/day) as empirical treatment. Blood tests for serum testosterone, estradiol, prolactin, luteinizing hormone, and follicle stimulating hormone were performed before and after 4 weeks of clomiphene use. Paired t-tests were used to evaluate the significance of the hormone level change. RESULTS: Overall, the patients' T/E2 ratio did not increase significantly after clomiphene use. In the subgroup analysis, the T/E2 ratio of patients with a baseline ratio of <200 increased significantly after clomiphene use. CONCLUSIONS: Clomiphene citrate may significantly increase the T/E2 ratio in eugonadal men under the premise of its ceiling effect (T/E2 ratio < 200), providing practitioners with guidance on the use of clomiphene in this demographic.

Outcomes of stratified transurethral resection of bladder tumor: A propensity score-matched analysis.

BACKGROUND/PURPOSE: Several strategies have been reported for improving the integrity of transurethral resection of bladder tumor (TURBT). However, no standard has been established. Stratified TURBT (SR) is one of protocols for TURBT, wherein exophytic tumors are first resected and retrieved, and tumor bases are then resected. In this study, we aimed to evaluate the outcomes of SR in patients with nonmuscle invasive bladder cancer (NMIBC). METHODS: From January 2012 to December 2017, patients newly diagnosed as having NMIBC with a follow-up period of more than 2 years were enrolled and categorized into SR and conventional TURBT (CR) groups. Propensity score matching at a 2:1 ratio was performed. Outcomes were the detrusor muscle sampling rate, recurrence-free survival (RFS), and progression-free survival (PFS). RESULTS: In total, 205 patients were included in our study. The detrusor muscle sampling rate was higher in the SR group (P = 0.043). After propensity score matching, 162 patients were selected for outcome analysis, with 108 and 54 patients undergoing SR and CR, respectively. Compared with the CR group, the SR group showed a lower recurrence rate (P = 0.015) and better RFS in univariate (P = 0.010) and multivariate (P = 0.006) Cox proportional hazards regression. Progression rate and PFS were not significantly different between the two groups. CONCLUSION: SR results in a higher detrusor muscle sampling rate and better disease outcomes. Our findings suggest that SR is a promising strategy for TURBT in patients with NMIBC.

Probing penile hemodynamics by using photoplethysmography as objective indicators for male erection quality and sexual function.

Erectile dysfunction (ED) is mostly due to the lack of blood flow into the penis. In the past 20 years, near-infrared spectroscopy (NIRS) was used in measuring the concentrations and temporal dynamics of different hemoglobin types. However, the dynamics of the light absorption (photoplethysmography; PPG) have not been applied to survey penile hemodynamics and erection quality. This paper compared the use of photoplethysmography (PPG) to study vascular ED with standard penile Doppler ultrasonography. Men diagnosed with vascular ED for at least 6 months and nominated for penile ultrasonography were included. PPG signals were collected during the ultrasound examination. All beat-to-beat PPG waveforms were aligned with the peak and averaged to one representative template waveform for feature analysis, including amplitude differences (APD) index, reflection time index (RTI), augmentation index (AI), and perfusion index (PI). An inverse correlation was found between end-erection amplitude and both erection hardness score (EHS) and resistive index (RI). APD index and EHS as well as the international index of erectile function-5 (IIEF) and RI were positively correlated. RTI and AI were inversely correlated to IIEF and RI. PI was positively correlated to RI. PPG may therefore be useful as a noninvasive, convenient, technique for sexual function evaluation.

Web- and Artificial Intelligence-Based Image Recognition For Sperm Motility Analysis: Verification Study.

BACKGROUND: Human sperm quality fluctuates over time. Therefore, it is crucial for couples preparing for natural pregnancy to monitor sperm motility. OBJECTIVE: This study verified the performance of an artificial intelligence-based image recognition and cloud computing sperm motility testing system (Bemaner, Createcare) composed of microscope and microfluidic modules and designed to adapt to different types of smartphones. METHODS: Sperm videos were captured and uploaded to the cloud with an app. Analysis of sperm motility was performed by an artificial intelligence-based image recognition algorithm then results were displayed. According to the number of motile sperm in the vision field, 47 (deidentified) videos of sperm were scored using 6 grades (0-5) by a male-fertility expert with 10 years of experience. Pearson product-moment correlation was calculated between the grades and the results (concentration of total sperm, concentration of motile sperm, and motility percentage) computed by the system. RESULTS: Good correlation was demonstrated between the grades and results computed by the system for concentration of total sperm (r=0.65, P<.001), concentration of motile sperm (r=0.84, P<.001), and motility percentage (r=0.90, P<.001). CONCLUSIONS: This smartphone-based sperm motility test (Bemaner) accurately measures motility-related parameters and could potentially be applied toward the following fields: male infertility detection, sperm quality test during preparation for pregnancy, and infertility treatment monitoring. With frequent at-home testing, more data can be collected to help make clinical decisions and to conduct epidemiological research.

Ambient sulfur dioxide could have an impact on testicular volume from a observational study on a population of infertile male.

BACKGROUND: The effect of ambient pollutants on the male reproductive system is controversial. This retrospective study investigated the effect of environmental pollutants on male reproductive health. METHODS: Male patients with primary infertility (n = 282) were identified from a single center between January 2016 and December 2017. Patients were physically examined for the presence of varicocele and for the volume of both testicles. Semen quality was measured in terms of the total sperm count, sperm concentration, and the percentage of sperm cells with motility and normal morphology. Data were acquired on the concentration of ambient pollutants, namely particulate matters of diameter < 2.5 µm, sulfur dioxide (SO2), nitrogen oxides (NOx), and ozone (O3), measured on daily and hourly basis, from the Environmental Protection Administration Executive Yuan, Taiwan. Individual exposure to pollutants was estimated based on the reported residential address of each participant. Statistical analysis indicated the effect of each pollutant on the testicular volume, sex hormone profile, and semen parameters. RESULTS: The mean ± standard deviation of age was 36.7 ± 7.3 years. The average sperm count and concentration were 41.9 million/mL and 34.1 million/mL, respectively. The mean levels of serum testosterone, follicle-stimulating hormone, and luteinizing hormone were 3.57 ± 1.68 ng/mL, 7.59 ± 6.3 IU/L, and 4.68 ± 3.49 IU/L, respectively. According to the multivariate linear regression model, NOx exposure was a risk factor for decreased sperm concentration and motility (p = 0.043 and 0.032). Furthermore, SO2 exposure was negatively associated and testicular volume (p < 0.01). CONCLUSIONS: NO2 and SO2 exposure were negatively associated with the seminal parameter and decreased testicular volume, respectively, in a population of men with infertility. However, additional prospective studies are needed to ascertain the cause-effect relation of current results.

Effect of diabetes mellitus and glycemic control on the prognosis of non-muscle invasive bladder cancer: a retrospective study.

BACKGROUND: Hyperglycemia is associated with series of process leading to oncogenesis. Evidence has shown that diabetes mellitus (DM) seems to be associated with poor prognosis in patients with bladder cancer. However, evidence on the effect of glycemic control on the outcomes of bladder cancer is still limited. In the current study, we aimed to investigate the effect of DM and glycemic control on the prognosis of bladder cancer. METHODS: We conducted a retrospective chart review of a prospective database from January 2012 to December 2017. Patients with newly diagnosed non-muscle invasive bladder cancer (NMIBC) were included. They were classified into the DM and non-DM groups. Prognosis including recurrence rate, progression rate, recurrence-free survival (RFS), and progression-free survival was compared between the two groups. Subgroup analysis of the DM subgroup, in which patients were classified by HbA1C level, was conducted to investigate the effect of glycemic control. RESULTS: A total of 287 patients were included in our study, with 61 patients in the DM group and 226 patients in the non-DM group. No statistically significant difference was found in the prognosis between the DM and non-DM groups. Subgroup analysis revealed higher recurrence rate (P = 0.037) and worse RFS (log-rank P = 0.019) in patients with HbA1C ≥ 7. CONCLUSIONS: DM is not a risk factor for recurrence and progression in patients with NMIBC. However, poor glycemic control is associated with poor prognosis in patients with both DM and NMIBC. Further prospective studies are needed to confirm current results.

Correction to: Androgen receptor regulates expression of skeletal muscle-specific proteins and muscle cell types.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Neddylation inhibitor, MLN4924 suppresses angiogenesis in huvecs and solid cancers: in vitro and in vivo study.

Cullin-RING E3 ligases are involved in the ubiquitination of substrates that regulate important biological processes and are a potential therapeutic target in many types of cancer. MLN4924, a small molecule of NEDD8-activating enzyme inhibitor, inactivates CRL by blocking cullin neddylation and has been reported to elicit anti-tumor effect. In this study, In this study, we aimed to investigate the effects of MLN4924 on angiogenesis in human umbilical vascular endothelial cells (HUVECs) and four types of cancer cells. Our results showed that MLN4924 inhibits cell viability and induced apoptosis in HUVECs in a dose-dependent manner. MLN4924 inhibits proliferation and interferes with the cell cycle checkpoint regulators, p21, p27, and phospho-histone H3. Vascular endothelial growth factor (VEGF) treatment increased the level of UBC12 in HUVECs, indicating that neddylation pathway is involved in VEGF-activated angiogenesis. MLN4924 decreased VEGF-activated cell proliferation via neddylation inhibition. MLN4924 inhibited VEGF-activated cell migration, capillary tube formation and VEGF-mediated Erk1/2 activation in HUVECs. We also examined antitumor effect of MLN4924 using xenograft SCID mouse models of four different types of cancer cells. The in vivo results showed MLN4924 inhibited tumor growth in all four types of cancers with decreasing CD31 expression in xenograft tumor. In conclusion, MLN4924 inhibited viability, migration, and VEGF-promoted angiogenic activity in HUVECs; consistently, MLN4924 inhibited tumor growth in four types of cancers with suppression of angiogenesis. These findings provide evidence to develop therapeutic strategy for cancer treatment through anti-angiogenesis through neddylation inhibition.

Preoperative %p2PSA and Prostate Health Index Predict Pathological Outcomes in Patients with Prostate Cancer Undergoing Radical Prostatectomy.

To evaluate the predictive accuracy of the %p2PSA and prostate health index (PHI) in predicting aggressive pathological outcomes in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP), we enrolled 91 patients with organ-confined PCa who were treated with robot-assisted RP. p2PSA levels and the PHI were investigated for their ability to predict pathological results. The %p2PSA and PHI were both significantly higher in patients with ≥pT3 disease, high-risk disease, positive surgical margin, or seminal vesical invasion (SVI). In univariable analysis, p2PSA derivatives were significant predictors of the presence of ≥pT3 disease, high-risk disease, positive surgical margin, and SVI. To predict adverse pathological outcomes at a sensitivity of 90%, p2PSA derivatives had higher specificity than standard PSA derivatives. In multivariable analysis, additional increases in the area under the receiver operating characteristic curve (AUC) were observed with the %p2PSA and PHI for ≥pT3 disease, high-risk disease, and positive surgical margin (8.2% and 2.7%, 6.2% and 4.1%, and 8.6% and 5.4%, respectively). A PHI ≥61.26 enhanced the predictive accuracy of the model for SVI by increasing the AUC from 0.624 to 0.819 (p = 0.009). The preoperative %p2PSA and PHI accurately predict adverse pathological results and are useful for decision-making.

The efficacy of pentosan polysulfate monotherapy for preventing recurrent urinary tract infections in women: A multicenter open-label randomized controlled trial.

BACKGROUND/PURPOSE: Pentosan polysulfate sodium (PPS), a semi-synthetic polysaccharide that adheres to bladder mucosa, is effective in treating interstitial cystitis. We evaluated the clinical benefit of PPS for the prevention of recurrent urinary tract infection (UTI) in women. METHODS: We conducted a multicenter, open-label, prospective, phase II, randomized controlled trial enrolling women with recurrent UTI ≥ 2 times in the past 6 months or ≥ 3 times in the past 12 months. Patients received oral PPS monotherapy for 16 weeks in treatment group. All patients were followed every 28 days until UTI recurrence or up to 112 days. The primary endpoint was the UTI recurrence-free survival. Adverse events were recorded as secondary endpoint. RESULTS: A total of 26 women were eligible for analysis. In the PPS group, none (0%) of the 12 patients had UTI recurrence during the study period. However, 9 (64%) of 14 patients had UTI recurrence in the control group. The UTI recurrence-free survival was significantly higher in the PPS group than in the control group (log-rank test p = 0.0004). One adverse event which led to discontinuation of the trial regimen was regarded as irrelevance of PPS treatment. The limitation was the small number of cases. CONCLUSION: Among women with recurrent UTI, 16-week PPS monotherapy significantly reduced UTI recurrence when compared with the control group.

Suppression of Angiogenesis by Targeting Cyclin-Dependent Kinase 7 in Human Umbilical Vein Endothelial Cells and Renal Cell Carcinoma: An In Vitro and In Vivo Study.

Cancer cells rely on aberrant transcription for growth and survival. Cyclin-dependent kinases (CDKs) play critical roles in regulating gene transcription by modulating the activity of RNA polymerase II (RNAPII). THZ1, a selective covalent inhibitor of CDK7, has antitumor effects in several human cancers. In this study, we investigated the role and therapeutic potential of CDK7 in regulating the angiogenic activity of endothelial cells and human renal cell carcinoma (RCC). Our results revealed that vascular endothelial growth factor (VEGF), a critical activator of angiogenesis, upregulated the expression of CDK7 and RNAPII, and the phosphorylation of RNAPII at serine 5 and 7 in human umbilical vein endothelial cells (HUVECs), indicating the transcriptional activity of CDK7 may be involved in VEGF-activated angiogenic activity of endothelium. Furthermore, through suppressing CDK7 activity, THZ1 suppressed VEGF-activated proliferation and migration, as well as enhanced apoptosis of HUVECs. Moreover, THZ1 inhibited VEGF-activated capillary tube formation and CDK7 knockdown consistently diminished tube formation in HUVECs. Additionally, THZ1 reduced VEGF expression in human RCC cells (786-O and Caki-2), and THZ1 treatment inhibited tumor growth, vascularity, and angiogenic marker (CD31) expression in RCC xenografts. Our results demonstrated that CDK7-mediated transcription was involved in the angiogenic activity of endothelium and human RCC. THZ1 suppressed VEGF-mediated VEGFR2 downstream activation of angiogenesis, providing a new perspective for antitumor therapy in RCC patients.

Author Correction: Comparison of Multipulse Laser Vaporesection versus Plasmakinetic Resection for Treatment of Benign Prostate Obstruction.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.