Outcomes in a contemporary cohort undergoing sacral neuromodulation using optimized lead placement technique.

AIMS: To evaluate factors associated with progression to stage 2 sacral neuromodulation (SNM) for refractory overactive bladder, urinary retention, or fecal incontinence using optimal lead placement techniques with curved stylet. METHODS: This is a retrospective analysis of a prospectively collected database of all consecutive stage 1 SNM lead placements at our institution between August 2014 and May 2017 using optimal lead placement technique with curved stylet. Patients with refractory overactive bladder, urinary retention, or fecal incontinence were enrolled. Patients with 50% or more symptom improvement on voiding diaries were offered stage 2 implant. Demographics, clinical, and surgical characteristics were compared for patients who underwent successful stage 2 implants versus those who underwent lead removal at the end of the stage 1 trial period. RESULTS: 127 patients underwent SNM during the study period. Motor thresholds of ≤2 mA in all four electrodes were achieved in 74% of patients (94/127). A total of 89.0% (113/127) of patients received stage 2 implants. The main indication for implant, specifically urgency urinary incontinence, was positively associated with progression to stage 2 implant. Male gender, history of pelvic pain and previous SNM were negatively associated with progression to stage 2 implant. CONCLUSIONS: Our findings demonstrate that the contemporary optimized lead placement technique resulted in low motor thresholds and successful progression to stage 2 SNM implant in the majority of our cohort. Predictive factors associated with success or failure may potentially guide decision making for therapeutic interventions and counseling patient expectations.

Analysis of the Completely Dry Rate Over Time After Mid-urethral Sling in a Real-world Clinical Setting.

OBJECTIVE: To improve patient counseling regarding mid-urethral slings (MUS), we performed an analysis of MUS patients dry at initial follow-up to evaluate probability of remaining dry over time, and analyzed clinical factors potentially influencing the probability of remaining dry. METHODS: A retrospective review of our prospectively-collected institutional database identified patients who underwent retropubic MUS (RMUS) or transobturator MUS (TMUS) between January 2001 and March 2016 and were completely dry, defined as an answer of "not at all" to UDI-6 question 3, at first follow-up within 1.5 years of surgery. Proportion remaining dry over time was estimated by Kaplan-Meier. Associated factors were evaluated using Cox proportional hazards modeling. Proportion with urge urinary incontinence at time of sling failure was assessed. RESULTS: Of 1102 patients undergoing MUS, 38.4% returned questionnaires and 47.5% of these were completely dry at initial follow-up (139 RMUS, 62 TMUS). Probability (95% CI, n = total patients) of remaining dry after RMUS at 3, 5, and 10 years was 72% (64%-81%, n = 70), 60% (51%-70%, n = 51), and 26% (18%-43%, n = 17). Probability estimates for TMUS at 3 and 5 years were 74% (62%-88%, n = 27) and 50% (35%-70%, n = 14). Obesity (Hazard ratio 2.22, P = .003) and age (Hazard ratio 1.043, P < .001) were associated with lower probability of remaining dry after RMUS. Of patients no longer completely dry at last follow-up, 72% RMUS and 75% TMUS had urge urinary incontinence. CONCLUSION: In our real-world cohort, patients who are dry within the first 1.5 years following MUS have ≥50% chance of remaining dry for 4 more years.

Indications for Augmentation Cystoplasty in the Era of OnabotulinumtoxinA.

Overactive bladder (OAB) with or without a neurogenic etiology that is refractory to conventional first-, second-, and third-line therapies is a challenging condition that typically leaves the physician and the patient with few options. Historically, treatment for patients who did not respond to any of the few pharmacologic choices focused on more invasive surgical options--specifically, augmentation cystoplasty (AC). In 2011 and 2013, the Food and Drug Administration (FDA) approved intradetrusor injection of onabotulinumtoxinA for the treatment of neurogenic detrusor overactivity (NDO) and idiopathic detrusor overactivity (IDO), respectively. Since then, a dramatic decline in the use of AC has called into question its utility in the treatment algorithm of this difficult patient population. The purpose of this paper is to review the current body of literature in order to outline the circumstances in which AC is still a relevant therapeutic option.

Abdominoscrotal hydrocele in infancy with incorporated epididymal tissue.

Abdominoscrotal hydrocele is a rare condition where a large hydrocele is connected to a preperitoneal space through the inguinal canal. We present a case of a young male with an abdominoscrotal hydrocele who showed gross absence of an epididymis upon hydrocele removal. Upon pathological examination, epididymal tissue was found to be incorporated into the wall of the hydrocele sac.

Nocturnal enuresis and overweight are associated with obstructive sleep apnea.

OBJECTIVE: The objective of this study was to examine the relationship of obstructive sleep apnea (OSA), body weight (BMI percentage [BMI%]), and monosymptomatic nocturnal enuresis (MNE) in children. METHODS: A case-control study design was used. All children were 5 to 15 years of age; case patients were recruited from a comprehensive sleep disorders center (n = 149), and control subjects were recruited from a general pediatric practice in the same catchment area (n = 139). Case patients were subject to overnight polysomnograms and grouped into apnea severity categories (minimal, mild, moderate, or severe) on the basis of respiratory disturbance index and minimum arterial oxygen saturation levels. Data for all children included age; gender; height; weight; and history of MNE, snoring, diabetes, nasal allergies, and/or enlarged tonsils. BMI% was used to group children into weight categories as suggested by the Centers for Disease Control and Prevention (underweight, normal weight, at risk for overweight, and overweight). Two age groupings were created (5-10 years and 11-15 years). Descriptive statistics provided the prevalence of OSA, weight category, and MNE among case patients and control subjects. Cross-tabulations examined the relationship of severity of OSA with weight categories and MNE, stratified by age and gender. A series of logistic regression models explored the interrelationship of the grouping variables. RESULTS: A large majority (79.9%) of control subjects were at risk for overweight, and a large majority (80.0%) of children with MNE also had some degree of OSA. Logistic regression demonstrated that both MNE (odds ratio: 5.29) and overweight (odds ratio 4.16) were significantly associated with OSA but not with each other. CONCLUSIONS: Overweight and MNE are associated with OSA but not with each other. OSA should be considered in overweight children with MNE, especially when they display other symptoms of OSA or fail to respond to standard MNE treatment programs.

Insights into cyclosporine A-induced atherosclerotic risk in transplant recipients: macrophage scavenger receptor regulation.

Clinical monitoring of organ-transplant recipients suggests that administration of cyclosporine (CsA) may increase the risk of atherosclerosis when compared with the general population. The purpose of this work is to demonstrate the utility of the in vitro Tamm-Horsfall protein (THP)-1 human monocyte cell culture model for determining drug-related atherosclerotic potential in macrophages. The effect of CsA on the mRNA expression of macrophage scavenger receptor genes including CD36, CD68, scavenger receptor (SR)-A, SR-BII, and lectin-like oxidized low-density lipoprotein receptor (LOX-1); the nuclear hormone receptors, including peroxisome-proliferator activated receptor (PPAR)gamma and liver-X-receptor (LXR)alpha; and the cholesterol efflux pump ABCA1 were investigated as markers of atherosclerotic progression. The THP-1 cells were cultured and differentiated into macrophages. The macrophages were then treated with CsA to assess gene expression. Time- (1, 2, 4, 8, and 24 hours) and dose- (concentrations [mg/L] corresponding to the trough [0.5], peak [1.25] and 4x peak [5]) dependency of CsA was assessed. The treated macrophage mRNA gene expression of CD36, CD68, and PPARgamma were up-regulated in the presence of CsA. Interestingly, SR-A, SR-BII, LOX-1, and LXRalpha expression appeared to be slightly down-regulated, and ABCA1 was relatively unchanged. Immunoblotting studies demonstrated that the protein expression of CD36 was unchanged or increased, PPARgamma was unchanged, and ABCA1 was unchanged or decreased at 4 and 8 hours. The results document CsA-induced mRNA and protein changes in receptors relevant to lipid-laden foam cell formation and demonstrate the utility of THP-1 macrophages for screening of atherosclerotic risk potential.

Effect of tacrolimus on the expression of macrophage scavenger and nuclear hormone receptors in THP-1-derived human macrophages.

BACKGROUND: Data indicate that tacrolimus and cyclosporine A (CsA) differentially affect the risk of atherosclerosis. The results of our recent in vitro studies of clinically relevant CsA concentrations demonstrated the modulation of macrophage scavenger receptors (MSRs) involved in atherogenesis. This work evaluated the effects of clinically relevant tacrolimus concentrations on the expression of the MSR genes CD36 and CD68, SR-A and SR-BII, lectin-like oxidized low-density lipoprotein receptor-1, the nuclear hormone receptors peroxisome proliferator-activated receptor (PPAR)gamma and liver-X-receptor-alpha, and the cholesterol efflux pump ABCA1 in the in vitro human THP-1 macrophage model. METHODS: The cells were cultured and differentiated into macrophages. Macrophages were treated with the tacrolimus to assess gene expression in a time-dependent (1, 2, 4, 8, and 24 hr) and dose-dependent (concentrations [micrograms/liter] corresponding to the trough [15], peak [30], and 4 x peak [120]) manner using reverse-transcriptase polymerase chain reactions. The gene expression levels of interest were normalized to GAPDH expression in each sample to provide semiquantitative reverse-transcriptase polymerase chain reaction results. Additional immunoblotting studies demonstrated protein expression of CD36, PPARgamma, and ABCA1. RESULTS.: The gene expression of CD36, SR-BII, and lectin-like oxidized low-density lipoprotein receptor-1 were down-regulated, and ABCA1 was up-regulated. CD68, SR-AI, liver-X-receptor-alpha, and PPARgamma were regulated in a dose-dependent manner. Protein expression of CD36 was down-regulated, and PPARgamma and ABCA1 were relatively unchanged. CONCLUSIONS: Tacrolimus seems to regulate MSRs, nuclear hormone receptors, and ABCA1 in THP-1 macrophages. These results differ from previous findings with CsA and may provide insight into the mechanisms of posttransplant atherosclerosis.