Enhancing Kidney Transplant Outcomes: The Impact of Living Donor Programs.

INTRODUCTION: The protocol for deceased donor kidney transplants has been standardised. The procedure for a living donor has peculiarities derived from the differences in the graft. When a living kidney donor program is implemented, changes occur in both the profile of the kidney transplant candidate and in the postoperative treatments. AIMS: To discover whether a living donor program influences the functional outcomes of kidney grafts in a longstanding classical deceased donor kidney transplant program and to identify the factors associated with transplant outcomes. METHODS: Retrospective observational multicentre study. SAMPLE: Kidney transplant patients in two urology referral centres for renal transplant in Spain between 1994 and 2019. Groups: TV (living transplant): patients given kidney transplants from living donors (n = 150); TCpre11 (deceased transplant previous to 2011): patients given kidney transplants from deceased donors before the living donor program was implemented (n = 650); and TCpost11 (deceased transplant after 2011): patients given kidney transplants from deceased donors after the living donor program was implemented (n = 500). RESULTS: Mean age was 55.75 years (18-80 years), higher in TCpre11. There were 493 female patients (37.92%) and 1007 male patients (62.08%). Mean body mass index (BMI) was 26.69 kg/m2 (17.50-42.78 kg/m2), higher in TCpre11. Mean ischemia time was 17.97 h (6-29 h), higher in TCpost11. Median duration of urethral catheter: 8 days (6-98 days), higher in TCpost11. Median duration of double-J ureteral stent: 58 days (24-180 days), higher in TCpost11. Pretransplant UTIs: 17.77%, higher in TCpre11 (25.69%) than in TV (12%), higher in TV (12%) than TCpost11 (9.2%), and higher in TCpre11 (25.69%) than TCpost11 (9.2%). Acute renal rejection in 9.33% of TV, 14.77% of TCpre11, and 9.8% of TCpost11. Multivariate analysis: TCpost11 featured higher BMI, more smoking, and chronic renal failure progression time. Lower use of nonantibiotic prophylaxis to prevent recurrent urinary tract infections, increased duration of urethral catheters due to obstructive problems, and favoured deterioration of kidney function was observed in the deceased donor program. The living donor (LD) program had a strong influence on deceased donor transplants in the prelysis phase. Implementation of a LD program was associated with a decrease in the likelihood of acute rejection in TCpost11 and an increase in the tendency towards normal kidney function. CONCLUSIONS: Implementing living donor transplant programs affects functional outcomes in deceased donor transplants, reducing the probability of acute rejection and increasing the tendency towards normal kidney function. Preventing recurrent urinary tract infections with measures other than antibiotics, smoking cessation, delaying the removal of the double-J stent from the graft, and pre-emptive transplant (transplant prior to dialysis) are associated with improved renal function of the graft.

Reducing Recurrent Urinary Tract Infections in Women with MV140 Impacts Personal Burden of Disease: Secondary Analyses of a Randomized Placebo-controlled Efficacy Study.

Background: Recurrent urinary tract infection (rUTI) remains a major health burden for women. A randomized, double-blind, placebo-controlled trial (RCT; NCT02543827) reported that female patients with rUTI receiving a sublingual vaccine, MV140, had a reduction in rUTI and increase in UTI-free rate compared with placebo. Objective: To determine the impact of MV140 on the personal burden of disease in women with rUTI using secondary endpoint data from the pivotal RCT evaluating MV140. Design setting and participants: In the primary RCT, female patients with rUTI enrolled in Spain and UK (from October 2015 to April 2019) were randomized to placebo (6 mo) or MV140 (3 or 6 mo), and followed for 12 mo. Individuals analyzed in this secondary analysis included those in the placebo and 3-mo (recommended dose) groups. Intervention: A polybacterial sublingual vaccine, MV140 (four inactivated whole-cell bacteria-Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, and Enterococcus faecalis), or placebo. Outcome measurements and statistical analysis: Symptom severity scoring, antibiotic use, safety, and multiple aspects of quality of life (QoL; Short-Form Questionnaire [SF-36]) were assessed. Results and limitations: Compared with the placebo group (n = 76), the 3-mo vaccinated group (n = 74) experienced fewer overall UTI symptoms (mean symptom score 102.2 ± 222.9 vs 194.2 ± 178.8; p = 0.0002), fewer days on antibiotics (12.4 ± 17.7 vs 28.7 ± 25.2; p = 0.0001), and improved total, general, and physical SF-36 QoL improvement (differences in means for total SF-36 score 15.7; 95% confidence interval [CI] 8.80, 22.64; p < 0.0001), with only social function QoL showing no impact (4.07; 95% CI -4.93, 13.08; p = 0.3744). Conclusions: Three months of MV140 is associated with a reduction of the personal burden of UTI by reducing overall UTI symptoms and antibiotic use, improving QoL in women with rUTI. Patient summary: Three months of MV140 vaccine, which has previously been shown to reduce the risk of urinary tract infection safely, is associated with a reduction in the personal burden of disease.

Relationship between Mental Disorders, Smoking or Alcoholism and Benign Prostate Disease.

INTRODUCTION: Mental disorders, smoking, or alcoholism and benign prostate disease are highly prevalent in men. AIMS: To identify the relationship between mental disorders, smoking, or alcoholism and benign prostate disease. METHODOLOGY: A prospective multicenter study that evaluated prostate health status in 558 men from the community. Groups: GP-men who request a prostate health examination and whose medical history includes a mental disorder, smoking, or alcoholism prior to a diagnosis of benign prostate disease; GU-men who request a prostate health examination and whose medical history includes a benign prostate disease prior to a diagnosis of mental disorder, smoking, or alcoholism. VARIABLES: age, body mass index (BMI), prostate specific antigen (PSA), follow-up of the mental disorder, smoking or alcoholism, time elapsed between urological diagnosis and the mental disorder, smoking or alcoholism diagnosis, status of the urological disease (cured or not cured), concomitant diseases, surgical history, and concomitant treatments. Descriptive statistics, Student's t-test, Chi2, multivariate analysis. RESULTS: There were no mental disorders, smoking, or alcoholism in 51.97% of men. Anxiety, smoking, major depressive disorder, pathological insomnia, psychosis, and alcoholism were identified in 19.71%, 13.26%, 5.73%, 4.30%, 2.87%, and 2.15% of individuals, respectively. Nonbacterial prostatitis (31.54%), urinary tract infection (other than prostatitis, 24.37%), prostatic intraepithelial neoplasia (13.98%), and prostatodynia (1.43%) were prostate diseases. Unresolved symptomatic benign prostate disease was associated with anxiety, depression, and psychosis (p = 0.002). Smoking was the disorder that men managed to eliminate most frequently. The dominant disorder in patients with symptomatic benign prostatic disease was alcoholism (p = 0.006). CONCLUSIONS: Unresolved symptomatic benign prostatic disease is associated with anxiety, depression, and psychosis. Alcoholism is associated with a worse prognosis in the follow-up of symptomatic benign prostatic disease.

Relationship between Prostate Inflammation and Periodontal Disease-A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis was to analyze the association between periodontal disease and prostate inflammation with a null hypothesis stating that periodontal disease does not increase the incidence of prostate inflammation. MATERIALS AND METHODS: A systematic literature review and meta-analysis of longitudinal observational cohort and case-control studies that evaluated the odds ratio or hazard ratio and confidence interval was undertaken based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations (2020). A total of four databases were consulted in the literature search: PubMed-Medline, Scopus, Embase, and Web of Science. After eliminating duplicated articles and applying the inclusion criteria, seven articles were selected for the qualitative and quantitative analyses. RESULTS: Four observational cohort studies and three observational cohort case-control studies were included in the meta-analysis. The four observational cohort studies were combined using the random effects model to estimate a hazard ratio of 1.32 with a confidence interval of 95% between 0.87 and 1.77. The meta-analysis presented high heterogeneity (Q test = 56.1; p value < 0.001; I2 = 94.9%). Moreover, the three observational case-control studies were combined using the random effects model to estimate an odds ratio of 1.62 with a confidence interval of 95% between 1.41 and 1.84. The meta-analysis presented high heterogeneity (Q test = 1.07; p value = 0.782; I2 = 0%). CONCLUSIONS: The incidence of periodontal disease does not increase the risk of the incidence of prostate inflammation.

One treatment with onabotulinumtoxinA relieves symptoms of overactive bladder in patients refractory to one or more oral medications.

INTRODUCTION AND HYPOTHESIS: Patients with overactive bladder (OAB) often undergo prolonged treatment with one or more oral OAB medications. OnabotulinumtoxinA (onabotA), a type A botulinum toxin, may provide an appropriate alternative to oral treatments in patients intolerant of or refractory to one or more oral OAB medications. The GRACE study demonstrated real-world benefits of onabotA treatment for OAB in patients refractory to oral medications. This exploratory post hoc analysis of data from the GRACE study aims to determine if treatment history impacts benefit from treatment with onabotA. METHODS: This is a subanalysis of the GRACE study, a prospective observational study (NCT02161159) that enrolled patients with symptomatic OAB inadequately managed by at least one oral OAB medication. Patients had a treatment history of one or more anticholinergics (AC) and/or ß-3 adrenoreceptor agonists (ß-3) for relief of OAB; results were stratified according to treatment history. Patients in this analysis elected to discontinue oral medications upon treatment with onabotA. Safety was followed for 12 months in all patients that received at least 1 dose of onabotA; efficacy was determined over a 12-week period. RESULTS: Compared to baseline levels, significant reductions in urinary incontinence (UI), urgency, micturition, and nocturia were noted as early as 1 week and were sustained at 12 weeks, regardless of the type and number of oral medications taken before treatment with onabotA. At 12 weeks post-onabotA, the mean change from baseline UI episodes/day for those with a treatment history of only one AC was -2.4 (n = 43, p ≤ 0.001); more than one AC, -2.4 (n = 52, p ≤ 0.001); one ß-3, -3.3 (n = 12, p < 0.05); at least one AC and at least one ß-3, -3.2 (n = 56, p ≤ 0.001). Pad and liner use was significantly decreased at 12 weeks post-onabotA across all treatment history groups. Reductions in diaper pant use varied, with less of a reduction in patients with a treatment history of more than one AC compared to patients with a history of at least one AC and one ß-3 (p < 0.05) or those with a history of only one AC (p < 0.05). Overall, a total of 253/288 of patients (88%) reported improvements on the treatment benefit scale 12 weeks after treatment with onabotA, regardless of type and number of prior oral medications. In the population of patients that received at least one dose of onabotA (N = 504), 57 adverse events were reported in 38 patients (7.5%); 9 were serious (1.8%). Urinary retention was reported in 5 patients (1.0%); 1 was severe (0.2%). Symptomatic urinary tract infection was reported in 2 patients (0.4%). CONCLUSIONS: In this exploratory post hoc analysis of real-world data from the GRACE study, there were few significant differences in outcomes based on the type and number of prior oral medications. Thus, patients who are refractory to one or more oral OAB medications may benefit from earlier treatment with onabotA.

Four vertex technique for correcting urethral prolapse: technique description and cohort study.

Introduction/Objectives: This study aims to describe the procedure and effectiveness of the four-vertex technique for correcting urethral prolapse in women. Methods and Materials: includes a retrospective case series of 17 patients who underwent surgery for urethral prolapse. Two study groups were distinguished based on the presence or absence of pelvic heaviness symptoms. The variables were analyzed, including age, BMI, concomitant diseases, obstetric and gynecological history, time from diagnosis to surgery, and outcomes of treatment. Results: All patients were postmenopausal, with a mean age at the time of the intervention of 70.41 years, with no differences between groups. Mean BMI was 23.67 kg/m2, higher in the group with a sensation of vaginal heaviness (p = 0.027). Mean time elapsed between diagnosis and operation was 231.58 days, with no differences between groups. Mean childbirth count was 2.29. The most frequent causes for consultation were urethrorrhagia (33.33%) and a bulging sensation (33.33%). After the intervention, 14 patients (82.35%) were asymptomatic, two (11.76%) had dysuria, and one (5.88%) had urinary urgency. Ten patients had pre-surgical urinary incontinence, which was resolved in nine patients. 17.46% subsequently presented pelvic organ prolapse. In three women there was secondary impairment of sexual activity. Conclusion: The four-vertex technique was effective in resolving symptoms in most patients. However, some patients experienced dysuria, urinary urgency, and pelvic organ prolapse after surgery. Urinary incontinence improved in most patients, but a few required additional treatments with suburethral tape. The study also identified associations between variables and the presence of cystocele, consultation for a bulging sensation, and bleeding from urethral prolapse. Overall, this study sheds light on the challenges and outcomes of surgical treatment for urethral prolapse and provides valuable insights for future research in this area.

Late diagnosis of ureteral injury from anterior lumbar spine interbody fusion surgery: Case report and literature review.

BACKGROUND: Anterior Lumbosacral Interbody Fusion (ALIF) is a type of back surgery with the advantages of direct access to the spinal interbody space and the potential lessening morbidity related to posterior approaches. PURPOSE: To describe a rare case of left ureteral lesion from ALIF surgery diagnosed 4 months after the procedure. CASE DESCRIPTION: A 37-year-old Caucasian man with a long history of painful post-traumatic spondylolisthesis and degenerative L5-S1 disc disease underwent a retroperitoneal anterior L5-S1 discectomy, insertion of an interbody tantallium cage, and placement of a pyramid titanium plate fixed with screws. Four months later, due to recurrent left lumbar pain and mild renal failure, a CT scan was performed showing left hydronephrosis with a homolateral urinoma of 17 cm in diameter. A left nephrostomy was placed and the nephrostography detected a filiform leakage at L5-S1 level in communication with the urinoma. The patient underwent laparoscopic urinoma drainage, distal left ureterectomy, and Casati-Boari flap ureterocystoneostomy with ureteral double J stent placement. The stent was held for six weeks and, 1 month later, the control ultrasound scan was negative for hydronephrosis, the creatinine level had normalized and the patient was asymptomatic. CONCLUSION: Ureteral lesion from ALIF surgery is a very rare event. Spinal surgeons should be more awareness regarding the susceptibility of ureteral injuries along with the clinical presentation, diagnostic work-up, and management options for this kind of complication.

Adverse Effects in Patients with Intellectual and Developmental Disabilities Hospitalized at the University Clinical Hospital.

(1) Background: Providing the patient with the health care they need in a personalized and appropriate manner and without adverse effects (AEs) is a part of quality of care and patient safety. The aim of this applied research project was the assessment of AEs as a clinical risk in patients with high social vulnerability such as persons with intellectual and developmental disabilities (PwIDD). (2) Methods: A retrospective epidemiological cohort study was performed on exposed and unexposed groups (the control group) in order to estimate the incidence of AEs in PwIDDs and assess their importance for this category of patients. (3) Results: AEs were observed with a frequency of 30.4% (95% CI) in the PwIDD exposed group, with significant differences to the unexposed group (p = 0.009). No differences were observed with regards to gender. Age was as a marker of care risk, with the highest incidence of AEs in the group of 60-69 years. (4) Conclusions: PwIDDs have a high risk of suffering AEs while receiving health care assistance due to their high social and clinical vulnerability. Health care practitioners must therefore be aware of these results and keep these observations in mind in order to carry out personalized, preventive, competent, effective, and safe medical care.

Sublingual MV140 for Prevention of Recurrent Urinary Tract Infections.

Sublingual MV140 for Prevention of Recurrent UTIThis randomized placebo-controlled trial tested MV140, a sublingual preparation of whole-cell inactivated bacteria, in women with recurrent urinary tract infection (UTI). MV140 administered sublingually for either 3 or 6 months decreased UTI incidence and prevented recurrence for up to 1 year compared with placebo, without serious adverse events.

Impact of whole-cell bacterial immunoprophylaxis in the management of recurrent urinary tract infections in the frail elderly.

PURPOSE: This study aimed to determine the effectiveness of whole-cell bacterial immunotherapy, i.e. MV140 and autovaccines, in reducing the number ofurinary tract infections (UTIs)in frail elderly patients with recurrent UTI (RUTI). METHOD: A prospective cohort observational study was performed including 200 frail elderly subjects suffering RUTI, both females and males, between 2016 and 2018. The effectiveness of autovaccines and the polybacterial formulation MV140 (Uromune®), consisting ofwhole-cell heat-inactivated Escherichia coli25%, Klebsiella pneumoniae25%, Proteus vulgaris25% andEnterococcus faecalis25% were evaluated. Subjects initiated a 3-month sublingually daily course with MV140 or autovaccine, either first treatment or a new course if they had been previously vaccinated prior to inclusion in the study. Number of UTIs and quality of life (QoL, SF-36 score) were measured in the different study groups. RESULTS: The mean age for participants was 82.67 (SD, 7.12) for female and 80.23 (SD, 11.12) for male subjects. In all groups, 12 months following bacterial immunotherapy, the number of UTIs significantly decreased compared to before the treatment with autovaccine or MV140: the rate of reduction ranged between 7- and 40-fold. An increase in QoL scoring was also observed in any study group. When comparing medical interventions, MV140 conferred significantly higher benefit than autovaccines. For previously vaccinated individuals, a new 3-month course with MV140 or autovaccines provided further clinical improvement. CONCLUSIONS: MV140 and autovaccines emerge as valuable immunoprophylaxis for the management of RUTI in the frail elderly, contributing to an improvement in patient's quality of life. Herein, MV140 has shown to confer a higher effectiveness compared to autovaccines, regardless sex or course of treatment.

Relationship between obstetric history and recurrent urinary infections.

Urinary tract infections affect more than 50% of women. 25% derive from recurrent UTI (RUTI). It is not known the relationship between obstetric history and RUTI occurrence. Investigate the relationship between obstetric events and RUTI. Multicenter observational retrospective study. Groups: G.RUTI (n = 294): women with RUTI; G.NON.RUTI (n = 126): women without RUTI (treated and cured of renal cancer). Descriptive statistics, ANOVA analysis of variance (with Scheffe's test for normal samples and Kruskal-Wallis for other distributions), Fisher's exact test, Pearson and Spearman correlation studies, and multivariate analysis multiple regression were used. Mean age 61.04 years (19-92), G.RUTI: 56.77 years SD 4.46 (19-85). G.NON.RUTI: 71 years SD 6.73 (25-92) (p = 0.0001). Obstetric history: Nulliparous G.RUTI: 20 (3.4%) G.NON.RUTI: 90 (71.42%) p 0.0001; Eutocic G.RUTI: 416 (70.74%) G.NON.RUTI: 30 (23.8%) p 0.0001. Dystocic G.RUTI: 58 (9.86%) G.NON.RUTI: 56 (44.44%) p 0.0001. G.RUTI abortion: 102 (17.34%) G.NON.RUTI: 30 (23.8%) p 0.1381. Hysterectomy without adnexectomy G.RUTI: 100 (17%) G.NON.RUTI: 18 (14.28%) p 0.5640. Hysterectomy with adnexectomy G.RUTI: 100 (17%) G.NON.RUTI: 66 (52.28%) p 0.0001. Nulliparity, dystocic delivery, and hysterectomy with adnexectomy are more frequent in women without RUTI, while eutocic births are more associated with RUTI. The most prevalent gynaecological-obstetric history in women with RUTI is eutocic delivery associated with a good health state.

Remeex® System Effectiveness in Male Patients with Stress Urinary Incontinence.

BACKGROUND: When conservative management fails, patients with stress urinary incontinence (SUI) are considered for surgical treatment. Simpler, more economical and less invasive surgical techniques, such as the Remeex® system, have been developed. OBJECTIVES: To analyze the objective effectiveness of the Remeex® system in the treatment of male stress urinary incontinence. To study survival and complication rates of the Remeex® system in male SUI patients. MATERIALS AND METHODS: Prospective observational study between July 2015 and May 2020. Group A (n = 7; GA) patients with mild SUI. Group B (n = 22; GB) patients with moderate SUI. Group C (n = 18; GC) patients with severe SUI. Effectiveness was assessed by the number of patients achieving complete and partial dryness. Complete dryness was defined as patients using 0-1 safety pads per day; partial dryness as a >50% reduction in the number of pads used. Results were analyzed using descriptive statistics, Student's t-test. Chi2, Fisher's exact test, ANOVA, and multivariate analysis. Significance was set at p < 0.05. RESULTS: Mean age 69.76 years, mean follow-up 33.52 months. Objective effectiveness was observed in 89.36% of patients with incontinence. The effectiveness was 85.71% in GA, 90.91% in GB and 88.89% in GC. There were no significant differences among groups (p = 1.0000). 34.04% of patients with an implant required at least one readjustment, while 66.00% did not require any. There were no significant differences among groups (p = 0.113) Chi2 = 4.352. 95.74% of implants remained in place by the end of follow-up. We observed complications in 17.02% of patients. CONCLUSIONS: Remeex® system is an effective and safe method for male stress urinary incontinence treatment, regardless of the severity of the incontinence, with high survival and low complication and removal rates. System readjustments are required in one-third of the cases.

Improvement in Quality of Life with Pelvic Floor Muscle Training and Biofeedback in Patients with Painful Bladder Syndrome/Interstitial Cystitis.

OBJECTIVE: To prove the benefits of pelvic floor muscle training with biofeedback (BFB) as a complementary treatment in women with bladder pain syndrome/interstitial cystitis (BPS/IC). METHODS: Prospective, randomized study in 123 women with BPS/IC. Groups: BFB+ (n = 48): women with oral drug treatment (perphenazine and amitriptyline) plus intravesical instillations (sodium hyaluronate) plus pelvic floor muscle training with BFB; BFB-: (n = 75): women with oral drug treatment plus intravesical instillations. VARIABLES: age, body mass index (BMI), time of follow-up, length of disease, time free of disease, diseases and health conditions concomitant, and responses to the SF-36 health-related quality of life questionnaire at the first consultation (SF-36 pre-treatment), and at the end of the study (SF-36 post-treatment). The treatment was considered successful when the SF-36 score reached values equal to or greater than 80 points or when the initial value increased by 30 or more points. RESULTS: Mean age was 51.62 years old (23-82). BMI was higher in BFB-. The mean length of BPS/IC condition was 4.92 years (1-20), shorter in BFB+ than in BFB-. Mean SF-36 score pre-treatment was 45.92 points (40-58), lower in BFB+ than in BFB-. Post-treatment SF-36 score was higher than pre-treatment SF-36 score both in BFB+ and BFB-. SF-36 values were higher in BFB+ compared to BFB- over the follow-up. CONCLUSIONS: BFB improves quality of life in women with BPS/IC as adjunct therapy to combined oral and intravesical treatment.

OnabotulinumtoxinA is a well tolerated and effective treatment for refractory overactive bladder in real-world practice.

INTRODUCTION AND HYPOTHESIS: In randomized clinical trials onabotulinumtoxinA was demonstrated to be an effective and well-tolerated treatment for overactive bladder (OAB) with urinary incontinence (UI). However, data reporting onabotulinumtoxinA use in everyday clinical practice are limited. Here, we present the results from a large, first-of-its-kind real-world study in patients with OAB. METHODS: This was a prospective, observational, multinational study (GRACE; ClinicalTrials.gov , NCT02161159) performed in four European countries. Patients (N = 504) aged ≥ 18 years with OAB inadequately managed with ≥ 1 anticholinergic received onabotulinumtoxinA per their physician's normal clinical practice. RESULTS: Physicians primarily used rigid cystoscopes for onabotulinumtoxinA injection; anesthesia/analgesia was utilized during most treatment procedures. Significant reductions in UI episodes/day from baseline to weeks 1 and 12 were observed as well as in micturition, urgency, and nocturia episodes/day. These improvements in urinary symptoms corresponded to higher scores on the treatment benefit scale at week 12. The use of other OAB medications dropped from baseline to weeks 1 and 12 and was sustained to week 52, which paralleled a reduction in the number of incontinence products used during that time frame. Adverse reactions were reported in 2.6% of patients throughout the study. CONCLUSIONS: In this real-world study, significant improvements in urinary symptoms were seen following onabotulinumtoxinA treatment as early as week 1 and sustained to at least week 12. This was accompanied by a reduced reliance upon incontinence products and reduction in concomitant OAB medication use. OnabotulinumtoxinA was well tolerated with no new safety signals.

A Double-Blind, Placebo-Controlled Parallel Group Study to Evaluate the Effect of a Single Oral Dose of 5-HT1A Antagonist GSK958108 on Ejaculation Latency Time in Male Patients Suffering From Premature Ejaculation.

BACKGROUND: Premature ejaculation (PE) is a common male neurobiological sexual disorder, related to a disturbance in central serotonin (5-hydroxytryptamine or 5-HT) neurotransmission. AIM: To assess the efficacy of a single oral dose of 5HT1A receptor antagonist GSK958108 on ejaculation latency time (ELT) in male subjects suffering from PE. METHODS: A total of 35 male subjects were enrolled in a Phase 1 double-blind, placebo-controlled, parallel group masturbation-model study. All subjects completed the study. No subject was withdrawn from the study. There were no major protocol deviations reported during the study. OUTCOMES: The primary outcome of the study was to evaluate the effect of a single oral dose of 5HT1A receptor antagonist GSK958108 on ELT as measured in the masturbation model; additionally, we investigated drug's safety and tolerability. RESULTS: In the 3 mg GSK958108 treatment group, the ELT was estimated to be 16% longer (1.542 vs 1.328, 95% CI: -16% to +61%) than if the subjects had taken placebo. In the 7 mg GSK958108 treatment group, the ELT was estimated to be 77% longer (2.346 vs 1.328, 95% CI: +28% to +144%) than in the placebo group. The systemic exposure to GSK958108 increased with dosage between 3 mg and 7 mg. A significant trend toward an increase of ELT was observed with increasing plasma concentrations of GSK958108. A total of 4 patients all treated with 7 mg dose experienced minor drug related adverse events (5 adverse events in 4 patients): somnolence (n = 3), headache (n = 1), tinnitus (n = 1). CLINICAL IMPLICATIONS: In the current double-blind, placebo-controlled parallel group study the 5HT1A receptor antagonist GSK958108 was tested in 3 mg and 7 mg doses for PE treatment in humans. It was shown that GSK958108 significantly delayed ejaculation showing a new and safe alternative in PE treatment. STRENGTHS & LIMITATIONS: The present study showed innovative results suggesting an important role of 5HT1A receptor antagonist in the PE treatment. However, the use of masturbation model and the small population are the main limitations of this investigation. CONCLUSION: 5HT1A receptor antagonist GSK958108 3 mg per day and 7 mg per day was found to be well-tolerated, safe and effective for the treatment of PE subjects and demonstrated a strong association between 5HT1A receptors and ejaculation control in humans (NCT00861484). Migliorini F, Tafuri A, Bettica P, et al. A Double-Blind, Placebo-Controlled Parallel Group Study to Evaluate the Effect of a Single Oral Dose of 5-HT1A Antagonist GSK958108 on Ejaculation Latency Time in Male Patients Suffering From Premature Ejaculation. J Sex Med 2021;18:63-71.

Increased urinary markers of kidney damage in the institutionalized frail elderly due to recurrent urinary tract infections.

OBJECTIVE: To characterize the impact on kidney injury of recurrent urinary tract infections (RUTI) in the frail elderly. METHODS: Prospective observational study in 200 frail elderly subjects for 1 year. Groups: GA (n = 100): subjects without RUTI, GB (n = 100): subjects with RUTI. Variables: age, concomitant diseases, glomerular filtration rate (GFR), urine neutrophil gelatinase-associated lipocalin (NGAL) at the beginning (NGAL-1) and end (NGAL-2) of the study, urine N-acetyl glucosaminidase (NAG) at the beginning (NAG-1) and the end (NAG-2) of the study, urine transforming growth factor-beta 1 (TGFß-1). Descriptive statistics, Mann-Whitney test, Chi-squared test, Fisher's exact test, and multivariate analysis were used. RESULTS: Mean age was 84.33 (65-99) years old, with no difference between GA and GB. Mean NGAL-1 was 1.29 ng/ml (0.04-8). There was lower in GA than in GB. Mean NGAL-2 was 1.41 ng/ml (0.02-9.22). NGAL-2 was lower in GA than in GB. Mean NAG-1 was 0.38 UU.II/ml (0.01-2.63. NAG-1 in GA was lower than in GB. Mean NAG-2 was 0.44 UU.II/ml (0-3.41). NAG-2 was lower in GA compared with GB. Mean TGFß-1 was 23.43 pg/ml (0.02-103.76). TGFß-1 was lower in GA than GB. There were no differences in the presence of secondary diagnoses between GA and GB. NAG-2 and NGAL-1 were the most determining factors of renal function; in GA it was NGAL-2, followed by NAG-1; in GB it was NGAL-1, followed by NAG-2. CONCLUSION: Frail elderly with RUTI have higher urinary levels of renal injury markers, specifically NGAL, NAG, and TGFß-1, chronically in periods between urinary tract infection (UTI). Urinary markers of renal injury, specifically NGAL, NAG, and TGFß-1, identify early deterioration of renal function, compared with serum creatinine, or albuminuria, in frail elderly with recurrent urinary infections.

The Association between Prostate-Specific Antigen Velocity (PSAV), Value and Acceleration, and of the Free PSA/Total PSA Index or Ratio, with Prostate Conditions.

INTRODUCTION: Prostate-specific antigen velocity (PSAV) is used to monitor men with clinical suspicion of prostate cancer (PCa), with a normal cut-off point of 0.3-0.5 ng/mL/year. The aim of the study is to establish the predictive capacity of PSAV (value and acceleration) and of the free PSA/total PSA index or ratio. METHOD: Prospective multicentre observational study in 2035 men of over 47 years of age. INCLUSION CRITERIA: men who wished to be informed on the health of their prostate. EXCLUSION CRITERIA: men with a previously diagnosed prostate condition. Groups: GA: (n = 518): men with serum PSA equal to or greater than 2.01 ng/mL. GB: (n = 775): men with serum PSA greater than or equal to 0.78 ng/mL and less than 2.01 ng/mL. GC: (n = 742): men with serum PSA less than 0.78 ng/mL. VARIABLES: prostate-specific antigen (PSA); age; body mass index (BMI); PSA velocity (PSAV) (ng/mL per year); free PSA/total PSA index (iPSA); PSAV acceleration (increasing: positive, or decreasing: negative); prostate diagnosis (benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), or infectious and non-infectious prostatitis and prostatic adenocarcinoma (PCa)); de novo diagnoses of urinary tract diseases or conditions; concomitant treatments, diseases and conditions; final diagnosis of prostate health. RESULTS: Mean age 62.35 years (SD 8.12), median 61 (47-94); age was lowest in GC. Mean BMI was 27.89 kg/m2 (SD 3.96), median 27.58 (18.56-57.13); no differences between groups. Mean PSAV was 0.69, SD 2.16, median 0.13 (0.001-34.46); PSAV was lowest in GC. Mean iPSA was 27.39 u/L (SD 14.25), median 24.29 (3.7-115); iPSA was lowest in GA. PSAV had more positive acceleration in GA and more negative acceleration in GC. There were 1600 (78.62%) cases of normal prostate or BPH, 322 (15.82%) cases of PIN or non-infectious prostatitis, and 113 (5.55%) cases of PCa. There were more cases of BPH in GC and more cases of PIN or prostatitis and cancer in GA (p = 0.00001). De novo diagnoses: 15 cases of urinary incontinence (UI), 16 discomfort/pain in LUT, 112 cases of voiding disorders, 12 urethral strictures, 19 hematuria, 51 cystitis, 3 pyelonephritis, 4 pelvic inflammatory disease; no differences were found between groups. In the multivariate analysis, PSAV and the direction of PSAV acceleration (positive or negative) were the variables which were correlated most strongly with prostate health. iPSA was associated with the presence of prostatitis, PCa, and BPH. Men in GA had more prostatitis, PCa, treatment with alpha blockers, and history of previous smoking. GB had more cases of BPH and more positive acceleration of PSAV. GC had more normal prostates, more BPH, more use of ranitidine, and more PSAV with negative acceleration. CONCLUSIONS: PSAV, direction of PSAV acceleration, and iPSA in PSA cut-off points of 0.78 ng/mL and 2.01 ng/mL in a priori healthy men over 47 predict the probability of benign or malignant pathology of the prostate.

Effects on Health-Related Quality of Life of Biofeedback Physiotherapy of the Pelvic Floor as an Adjunctive Treatment Following Surgical Repair of Cystocele.

OBJECTIVES: to demonstrate the benefits of physiotherapy (PT) with pelvic floor biofeedback (BFB) in improving health-related quality of life when used as a complementary therapy after surgical treatment of cystocele, in cases in which perineal pain or discomfort persists. MATERIALS AND METHODS: prospective observational study in 226 women who received complementary therapy after surgical treatment of cystocele due to persistent perineal discomfort or pain. Groups: GA (n = 78): women treated with 25 mg of oral pregabalin every 12 h plus BFB, consisting of 20 once-weekly therapy sessions, each 20 min long, with perineal pregelled surface electrodes connected to a screen which provides visual feedback; GB (n = 148): women treated with oral pregabalin 25 mg every 12 h without BFB. VARIABLES: age, body mass index (BMI), time since onset of cystocele prior to surgery (TO), SF-36 health-related quality of life survey score, diseases and concomitant health conditions, follow-up time, success, or failure of postsurgical treatment. RESULTS: average age 67.88 years (SD 12.33, 30-88), with no difference between GA and GB. Average body mass index (BMI) 27.08 (SD 0.45, 18.74-46.22), with no difference between GA and GB. Time since onset of cystocele prior to surgery (TO) was 6.61 years (SD 0.6), with no difference between GA and GB. Pretreatment SF-36 score was lower in GA success than GB success. Treatment was successful in 141 (63.20%) women and failed in 82 (36.80%). PT and age were the main predictors of success, and the least important were pretreatment SF-36 and the time elapsed after the intervention. In GA, 63 women (80.80%) showed improvement while 15 (19.20%) did not. Age was the main predictor of treatment success, while the least important was BMI. In GB, 78 women (53.80%) showed improvement while 67 (46.20%) did not improve. The main predictor was time since cystocele onset prior to surgery, while the least important was age. The odds ratio (OR) of improving quality of life for each unit increase in SF-36 was 11.5% (OR = 0.115) in all patients, with no difference between success and failure; in GA it was 23.80% (OR = 0.238), with a difference between success and failure; in GB it was 11.11% (OR = 0.111), with no difference between success and failure. GA and GB success had more history of eutocic delivery. GA success had more rUTI. GB success and GA failure both had more history of UI corrective surgery. The "failure" outcome had a higher number of patients with more than two concomitant pathological conditions. CONCLUSIONS: BFB as an adjunctive treatment improves quality of life in women suffering from persistent discomfort after surgery for cystocele. Young women who meet the criteria for recurrent urinary tract infection or who have a history of eutocic delivery show greater improvement. Body mass index does not influence response to treatment, while the presence of more than two concomitant conditions indicates a poor prognosis for improving quality of life.

Benefits of Physiotherapy on Urinary Incontinence in High-Performance Female Athletes. Meta-Analysis.

Introduction: High performance female athletes may be a risk group for the development of urinary incontinence due to the imbalance of forces between the abdomen and the pelvis. Pelvic floor physiotherapy may be a useful treatment in these patients. Objectives: (1) To identify the scientific evidence for pelvic floor (PF) dysfunctions that are associated with urinary incontinence (UI) in high-performance sportswomen. (2) To determine whether pelvic floor physiotherapy (PT) corrects UI in elite female athletes. Materials and methods: Meta-analysis of published scientific evidence. The articles analyzed were found through the following search terms: (A) pelvic floor dysfunction elite female athletes; (B) urinary incontinence elite female athletes; (C) pelvic floor dysfunction elite female athletes physiotherapy; (D) urinary incontinence elite female athletes physiotherapy. Variables studied: type of study, number of individuals, age, prevalence of urinary incontinence described in the athletes, type of sport, type of UI, aspect investigated in the articles (prevalence, response to treatment, etiopathogenesis, response to PT treatment, concomitant health conditions or diseases. Study groups according to the impact of each sport on the PF: G1: low-impact (noncompetitive sports, golf, swimming, running athletics, throwing athletics); G2: moderate impact (cross-country skiing, field hockey, tennis, badminton, baseball) and G3: high impact (gymnastics, artistic gymnastics, rhythmic gymnastics, ballet, aerobics, jump sports (high, long, triple and pole jump)), judo, soccer, basketball, handball, volleyball). Descriptive analysis, ANOVA and meta-analysis. Results: Mean age 22.69 years (SD 2.70, 18.00-29.49), with no difference between athletes and controls. Average number of athletes for each study was 284.38 (SD 373,867, 1-1263). The most frequent type of study was case-control (39.60%), followed by cross-sectional (30.20%). The type of UI was most often unspecified by the study (47.20%), was stress UI (SUI, 24.50%), or was referred to as general UI (18.90%). Studies on prevalence were more frequent (54.70%), followed by etiopathogenesis (28.30%) and, lastly, on treatment (17.00%). In most cases sportswomen did not have any disease or concomitant pathological condition (77.40%). More general UI was found in G1 (36.40%), SUI in G2 (50%) and unspecified UI in G3 (63.64%). In the meta-analysis, elite athletes were found to suffer more UI than the control women. In elite female athletes, in general, physiotherapy contributed to gain in urinary continence more than in control women (risk ratio 0.81, confidence interval 0.78-0.84)). In elite female athletes, former elite female athletes and in pregnant women who regularly engage in aerobic activity, physiotherapy was successful in delivering superior urinary continence compared to the control group. The risk of UI was the same in athletes and in the control group in volleyball female athletes, elite female athletes, cross-country skiers and runners. Treatment with PT was more effective in control women than in gymnastics, basketball, tennis, field hockey, track, swimming, volleyball, softball, golf, soccer and elite female athletes. Conclusions: There is pelvic floor dysfunction in high-performance athletes associated with athletic activity and urinary incontinence. Eating disorders, constipation, family history of urinary incontinence, history of urinary tract infections and decreased flexibility of the plantar arch are associated with an increased risk of UI in elite female athletes. Pelvic floor physiotherapy as a treatment for urinary incontinence in elite female athletes, former elite female athletes and pregnant athletes who engage in regular aerobic activity leads to a higher continence gain than that obtained by nonathlete women.

The American Society of Anesthesiologists Physical Status (ASA-PS) Risk Group Classification Can Be Used to Anticipate Functional Recovery Outcomes after the Surgical Treatment of Female Urinary Incontinence with Transobturator Suburethral Tape.

INTRODUCTION: Stress urinary incontinence (SUI) has an incidence of 15-80% in women. One of the most widely used surgical techniques for treatment is the placement of a suburethral transobturator tape (TOT). Although this technique has a relatively low morbidity rate, it is not exempt from intraoperative or postoperative complications, which can have an impact on functional recovery, understood as the return to routine life prior to the intervention. AIMS: To assess the time for functional recovery in women operated on for SUI by TOT; to identify complications and related factors, according to anaesthetic risk, which condition the time to functional recovery; and proposals for improvements in the prevention of possible complications and in reducing functional recovery time. MATERIALS AND METHODS: A non-concurrent prospective observational multicenter study of 891 women undergoing TOT for stress urinary incontinence since 1 April 2003, who were successful in achieving urinary continence (completely dry). Study groups: GA (n = 443): patients with ASA I risk. GB (n = 306): patients with ASA II risk. GC (n = 142): patients with anaesthetic risk ASA III. Investigated variables: age, body mass index, follow-up time, secondary diagnoses, surgical history, obstetric-gynecological history, toxic habits, and complications derived from surgery: bleeding, pain, infection. Descriptive statistics, Student's t test, Chi2, Fisher, ANOVA, multivariate analysis, significance for p < 0.05. RESULTS: Mean age was 60.10 years (SD13.38), with no difference between groups. Mean body mass index (BMI) was 26.55 kg/m2 (SD 4.51), lowest in GA. GB had more HT (38.6%) than GC (23.23%), more type 2 diabetes (19.83% versus 10.56%), and more respiratory disorders (6.97% versus 2.11%). There were more women with anxiety in GB (19.3%) than in GC (6.33%) (p = 0.0221) and GA (10.51%) (p = 0.0004). There was more hypothyroidism in GB (16.08%) compared to GC (2.11%) and GA (9.07%). There was more history of curettage in GC (11.97%) versus GB (5.63%); and more pelvic surgery in GB (71.31%) and GC (66.9%) compared to GA (32.57%). There were more concomitant treatments with benzodiazepines in GC (27.46%) and GB (28.41%) than in GA (8.86%), and more parapharmacy treatments in GB (17.96%) than in GC (6.33%). Following the operation, 113 patients had some sign or symptom that required medical attention: in GA 48 (10.83%), in GB 49 (16.06%), in GC 16 (13.22%). Mean days until functional recovery in patients with complications: in GA 5.72 (SD2.05); bleeding 3 (SD1), pain 6.40 (SD1.34), and infection 7.33 (SD0.57), with fewer days for bleeding than for pain or infection. GB: 27.96 (SD 28.42), bleeding 3 (SD0), pain 46.69 (SD31.36), infection 10.83 (SD3.90); lowest for patients with bleeding. GC: 9.44 (SD 2.50); for bleeding 7.66 (SD2. 08), pain 10.66 (SD1.15), infection 10 (SD3.46); no differences. Overall, for women with bleeding, the time was 4.16 days (SD1.94); less in GA and GB than in GC. Pain, at 31.33 days (SD 30.70), was the factor that most delayed functional recovery; in GB women, it took longer to return to work due to pain (45.96, SD31.36) compared to GA (6.4, SD 1.34) and GC (10.66, SD1.15). In women with infection, overall mean time was 10.11 days (SD 3.61) with no difference between groups. CONCLUSIONS: Mean time for the return to normal activity in patients who underwent TOT for SUI is 5 days if there are no complications, and 16.91 days if there are any. The ASA-SP risk group classification can be used to anticipate functional outcomes. An ASA-PS risk-based functional recovery forecasting protocol should be adapted, especially ASA II patients who may present with long-term disabling postoperative pain. Preventive management measures are proposed that favour functional recovery.