Management of male stress urinary incontinence in high-risk patients: a narrative review.

Background and Objective: The artificial urinary sphincter (AUS) remains the gold standard for treatment of stress urinary incontinence (SUI). However, highly complex patients such as those with bulbar urethral compromise, bladder pathology, and lower urinary complications pose a particular challenge for the surgeon. In this article, we will address critical risk factors and synthesize existent data across relevant disease states to support surgeons in successful management of SUI in high-risk patients. Methods: A comprehensive review of current literature was performed utilizing the search term "artificial urinary sphincter" in conjunction with any of the following additional terms: "radiation", "urethral stricture", "posterior urethral stenosis", "vesicourethral anastomotic stenosis", "bladder neck contracture", "pelvic fracture urethral injury", "penile revascularization", "inflatable penile prosthesis", and "erosion". Guidance is provided based upon expert opinion where existing literature was sparse or nonexistent. Key Content and Findings: Several known patient risk factors are associated with AUS failure and can ultimately lead to device explantation. Each risk factor requires careful consideration and investigation, or intervention as appropriate, prior to device placement. Optimization of urethral health, confirmation of anatomic and functional stability of the lower urinary tract, and thorough patient counseling are a necessity for these high-risk patients. Several surgical strategies to decrease device complications can be considered: optimization of testosterone, avoidance of 3.5 cm AUS cuff, transcorporal AUS cuff placement, relocation of AUS cuff site, use of lower pressure-regulating balloon, penile revascularization, and intermittent nocturnal deactivation. Conclusions: A number of patient risk factors are associated with AUS failure and can ultimately lead to device explantation. We present an algorithm for management of high-risk patients. Optimization of urethral health, confirmation of anatomic and functional stability of the lower urinary tract, and thorough patient counseling are a necessity for these high-risk patients.

Outcomes of Alternative Reservoir Placement in the Lateral Retroperitoneum During Inflatable Penile Prosthesis Placement.

OBJECTIVES: To describe outcomes of reservoir placement, exchange, and extraction from the lateral retroperitoneum (LR) in complex patients with a three-piece inflatable penile prosthesis (IPP). METHODS: A retrospective chart review was performed on all patients that underwent placement of an IPP from 2009 to 2019. Patients with placement of the reservoir in the LR were identified. Intraoperative complications during reservoir placement, exchange, or removal, reservoir-related outcomes, and secondary device-related outcomes were collated and compared to patients who underwent traditional Space of Retzius reservoir placement. RESULTS: A total of 587 men underwent primary IPP placement with 321 patients undergoing reservoir placement in the SOR and 266 in the LR. No significant differences were found in intra-operative reservoir-related outcomes (P=.272) between the 2 groups during placement, replacement, or extraction. Bowel injury occurred in 1 patient in the LR group during placement. No significant differences were found in postoperative reservoir complications (P= .534). Both groups each had one instance of patient reported bulge and pain at reservoir site (P= .6777). Two (0.6%) patients in the SOR group and 3 (1.1%) patients in the LR group had a reservoir failure or leak. There was a trend towards a lower rate of device infections in the LR group (1.9%) compared to the SOR group (4.7%) (P= .063). There were no significant differences in overall device mechanical failure rates between both groups (P= .919). CONCLUSIONS: Reservoir placement in the LR is safe in patients with complex pelvic anatomy with equivalent device durability and no difference in surgical outcomes compared to standard retropubic reservoir placement.

Polymorphic allele of human IRGM1 is associated with susceptibility to tuberculosis in African Americans.

An ancestral polymorphic allele of the human autophagy-related gene IRGM1 is associated with altered gene expression and a genetic risk for Crohn's Disease (CD). We used the single nucleotide polymorphism rs10065172C/T as a marker of this polymorphic allele and genotyped 370 African American and 177 Caucasian tuberculosis (TB) cases and 180 African American and 110 Caucasian controls. Among African Americans, the TB cases were more likely to carry the CD-related T allele of rs10065172 (odds ratio of 1.54; 95% confidence interval, 1.17-2.02; P<0.01) compared to controls. Our finding suggests that this CD-related IRGM1 polymorphic allele is also associated with human susceptibility to TB disease among African Americans.

Active site threonine facilitates proton transfer during dioxygen activation at the diiron center of toluene/o-xylene monooxygenase hydroxylase.

Toluene/o-xylene monooxygenase hydroxylase (ToMOH), a diiron-containing enzyme, can activate dioxygen to oxidize aromatic substrates. To elucidate the role of a strictly conserved T201 residue during dioxygen activation of the enzyme, T201S, T201G, T201C, and T201V variants of ToMOH were prepared by site-directed mutagenesis. X-ray crystal structures of all the variants were obtained. Steady-state activity, regiospecificity, and single-turnover yields were also determined for the T201 mutants. Dioxygen activation by the reduced T201 variants was explored by stopped-flow UV-vis and Mössbauer spectroscopy. These studies demonstrate that the dioxygen activation mechanism is preserved in all T201 variants; however, both the formation and decay kinetics of a peroxodiiron(III) intermediate, T201(peroxo), were greatly altered, revealing that T201 is critically involved in dioxygen activation. A comparison of the kinetics of O(2) activation in the T201S, T201C, and T201G variants under various reaction conditions revealed that T201 plays a major role in proton transfer, which is required to generate the peroxodiiron(III) intermediate. A mechanism is postulated for dioxygen activation, and possible structures of oxygenated intermediates are discussed.

Effect of dietary sodium on vasoconstriction and eNOS-mediated vascular relaxation in caveolin-1-deficient mice.

Changes in dietary sodium intake are associated with changes in vascular volume and reactivity that may be mediated, in part, by alterations in endothelial nitric oxide synthase (eNOS) activity. Caveolin-1 (Cav-1), a transmembrane anchoring protein in the plasma membrane caveolae, binds eNOS and limits its translocation and activation. To test the hypothesis that endothelial Cav-1 participates in the dietary sodium-mediated effects on vascular function, we assessed vascular responses and nitric oxide (NO)-mediated mechanisms of vascular relaxation in Cav-1 knockout mice (Cav-1-/-) and wild-type control mice (WT; Cav-1+/+) placed on a high-salt (HS; 4% NaCl) or low-salt (LS; 0.08% NaCl) diet for 16 days. After the systolic blood pressure was measured, the thoracic aorta was isolated for measurement of vascular reactivity and NO production, and the heart was used for measurement of eNOS expression and/or activity. The blood pressure was elevated in HS mice treated with NG-nitro-l-arginine methyl ester and more so in Cav-1-/- than WT mice and was significantly reduced during the LS diet. Phenylephrine caused vascular contraction that was significantly reduced in Cav-1-/- (maximum 0.25 +/- 0.06 g/mg) compared with WT (0.75 +/- 0.22 g/mg) on the HS diet, and the differences were eliminated with the LS diet. Also, vascular contraction in response to membrane depolarization by high KCl (96 mM) was reduced in Cav-1-/- (0.27 +/- 0.05 g/mg) compared with WT mice (0.53 +/- 0.12 g/mg) on the HS diet, suggesting that the reduced vascular contraction is not limited to a particular receptor. Acetylcholine (10(-5) M) caused aortic relaxation in WT mice on HS (23.6 +/- 3.5%) and LS (23.7 +/- 5.5%) that was enhanced in Cav-1-/- HS (72.6 +/- 6.1%) and more so in Cav-1-/- LS mice (93.6 +/- 3.5%). RT-PCR analysis indicated increased eNOS mRNA expression in the aorta and heart, and Western blots indicated increased total eNOS and phosphorylated eNOS in the heart of Cav-1-/- compared with WT mice on the HS diet, and the genotypic differences were less apparent during the LS diet. Thus Cav-1 deficiency during the HS diet is associated with decreased vasoconstriction, increased vascular relaxation, and increased eNOS expression and activity, and these effects are altered during the LS diet. The data support the hypothesis that endothelial Cav-1, likely through an effect on eNOS activity, plays a prominent role in the regulation of vascular function during substantial changes in dietary sodium intake.