Nickel-Catalyzed Electrochemical Cross-Electrophile C(sp2)-C(sp3) Coupling via a NiII Aryl Amido Intermediate.

Cross-electrophile coupling (XEC) between aryl halides and alkyl halides is a streamlined approach for C(sp2)-C(sp3) bond construction, which is highly valuable in medicinal chemistry. Based on a key NiII aryl amido intermediate, we developed a highly selective and scalable Ni-catalyzed electrochemical XEC reaction between (hetero)aryl halides and primary and secondary alkyl halides. Experimental and computational mechanistic studies indicate that an amine secondary ligand slows down the oxidative addition process of the Ni-polypyridine catalyst to the aryl bromide and a NiII aryl amido intermediate is formed in situ during the reaction process. The relatively slow oxidative addition is beneficial for enhancing the selectivity of the XEC reaction. The NiII aryl amido intermediate stabilizes the NiII-aryl species to prevent the aryl-aryl homo-coupling side reactions and acts as a catalyst to activate the alkyl bromide substrates. This electrosynthesis system provides a facile, practical, and scalable platform for the formation of (hetero)aryl-alkyl bonds using standard Ni catalysts under mild conditions. The mechanistic insights from this work could serve as a great foundation for future studies on Ni-catalyzed cross-couplings.

Electro/Ni Dual-Catalyzed Decarboxylative C(sp3)-C(sp2) Cross-Coupling Reactions of Carboxylates and Aryl Bromide.

Paired redox-neutral electrolysis offers an attractive green platform for organic synthesis by avoiding sacrificial oxidants and reductants. Carboxylates are non-toxic, stable, inexpensive, and widely available, making them ideal nucleophiles for C-C cross-coupling reactions. Here, we report the electro/Ni dual-catalyzed redox-neutral decarboxylative C(sp3)-C(sp2) cross-coupling reactions of pristine carboxylates with aryl bromides. At a cathode, a NiII(Ar)(Br) intermediate is formed through the activation of Ar-Br bond by a NiI-bipyridine catalyst and subsequent reduction. At an anode, the carboxylates, including amino acid, benzyl carboxylic acid, and 2-phenoxy propionic acid, undergo oxidative decarboxylation to form carbon-based free radicals. The combination of NiII(Ar)(Br) intermediate and carbon radical results in the formation of C(sp3)-C(sp2) cross-coupling products. The adaptation of this electrosynthesis method to flow synthesis and valuable molecule synthesis was demonstrated. The reaction mechanism was systematically studied through electrochemical voltammetry and density functional theory (DFT) computational studies. The relationships between the electrochemical properties of carboxylates and the reaction selectivity were revealed. The electro/Ni dual-catalyzed cross-coupling reactions described herein expand the chemical space of paired electrochemical C(sp3)-C(sp2) cross-coupling and represent a promising method for the construction of the C(sp3)-C(sp2) bonds because of the ubiquitous carboxylate nucleophiles and the innate scalability and flexibility of electrochemical flow-synthesis technology.

Understanding Formation and Roles of NiII Aryl Amido and NiIII Aryl Amido Intermediates in Ni-Catalyzed Electrochemical Aryl Amination Reactions.

Ni-catalyzed electrochemical aryl amination (e-amination) is an attractive, emerging approach to building C-N bonds. Here, we report in-depth experimental and computational studies that examined the mechanism of Ni-catalyzed e-amination reactions. Key NiII-amine dibromide and NiII aryl amido intermediates were chemically synthesized and characterized. The combination of experiments and DFT calculations suggest (1) there is coordination of an amine to the NiII catalyst before the cathodic reduction and oxidative addition steps, (2) a stable NiII aryl amido intermediate is produced from the cathodic half-reaction, a critical step in controlling the selectivity between cross-coupling and undesired homo-coupling reaction pathways, (3) the diazabicycloundecene additive shifts the aryl halide oxidative addition mechanism from a NiI-based pathway to a Ni0-based pathway, and (4) redox-active bromide in the supporting electrolyte functions as a redox mediator to promote the oxidation of the stable NiII aryl amido intermediate to a NiIII aryl amido intermediate. Subsequently, the NiIII aryl amido intermediate undergoes facile reductive elimination to provide a C-N cross-coupling product at room temperature. Overall, our results provide new fundamental understandings about this e-amination reaction and guidance for further development of other Ni-catalyzed electrosynthetic reactions such as C-C and C-O cross-couplings.

Mechanistic studies of Ni-catalyzed electrochemical homo-coupling reactions of aryl halides.

Ni-catalyzed electrochemical arylation is an attractive, emerging approach for molecular construction as it uses air-stable Ni catalysts and efficiently proceeds at room temperature. However, the homo-coupling of aryl halide substrates is one of the major side reactions. Herein, extensive experimental and computational studies were conducted to examine the mechanism of Ni-catalyzed electrochemical homo-coupling of aryl halides. The results indicate that an unstable NiII(Ar)Br intermediate formed through oxidative addition of the cathodically generated NiI species with aryl bromide and a consecutive chemical reduction step. For electron-rich aryl halides, homo-coupling reaction efficiency is limited by the oxidative addition step, which can be improved by negatively shifting the redox potential of the Ni-catalyst. DFT computational studies suggest a NiIII(Ar)Br2/NiII(Ar)Br ligand exchange pathway for the formation of a high-valent NiIII(Ar)2Br intermediate for reductive elimination and production of the biaryl product. This work reveals the reaction mechanism of Ni-catalyzed electrochemical homo-coupling of aryl halides, which may provide valuable information for developing cross-coupling reactions with high selectivity.

Directing-Group-Free Arene C(sp2)-H Amination Using Bulky Aminium Radicals and DFT Analysis of Regioselectivity.

A hydroxylamine-derived electrophilic aminating reagent produces a transient and bulky aminium radical intermediate upon in situ activation by either TMSOTf or TFA and a subsequent electron transfer from an iron(II) catalyst. Density functional theory calculations were used to examine the regioselectivity of arene C-H amination reactions on diversely substituted arenes. The calculations suggest a simple charge-controlled regioselectivity model that enables prediction of the major C(sp2)-H amination product.

Long-term outcomes of anastomotic urethroplasty for radiation-induced strictures.

PURPOSE: To present our experience with excision and primary anastomosis (EPA) of radiation-induced urethral strictures (RUS) in men, including risk factors for stricture recurrence and long-term recurrence rates. METHODS: A retrospective review was performed of patients who underwent EPA of RUS between 2007 and 2018 at a single tertiary referral center. Demographic information, stricture location and length, complications, and stricture recurrence were analyzed. Univariate and multivariate Cox regression analyses were performed to identify variables impacting recurrence. RESULTS: EPA was performed in 116 patients with RUS. The majority of patients (86.2%, 100/116) underwent at least one prior urologic intervention. Mean stricture length was 2.3 cm. Stricture recurrence occurred in 19.0% (22/116) at a mean of 8.6 months. For patients with at least 1 year of postoperative follow-up (mean 30.7 months), stricture recurrence significantly increased to 36.6% (15/41; p = 0.03). On univariate and multivariate analyses, postoperative complications were associated with stricture recurrence (p < 0.001). CONCLUSION: EPA remains a viable option for men with RUS. Nearly two-thirds of RUS patients remain recurrence-free with long-term follow-up following EPA.

Strong correlation between standing cough test and 24-hour pad weights in the evaluation of male stress urinary incontinence.

AIMS: We sought to compare in-office physical exam findings via standing cough test (SCT) versus 24-hour pad weights among men seeking treatment for postprostatectomy stress urinary incontinence (SUI). METHODS: A retrospective review of a single surgeon database of incontinence procedures was performed. Documentation of SUI severity (grades 0-4) was completed by SCT preoperatively utilizing the Male Stress Incontinence Grading Scale (MSIGS). All patients had pads per day (PPD) and 24-hour pad weights obtained. We determined the Spearman's correlation coefficient between these variables. RESULTS: We identified 104 men who underwent anti-incontinence surgery (AdVance Sling or artificial urinary sphincter [AUS]). In the sling group (65 patients), nearly all (97%) had minimal incontinence with SCT (MSIGS = 0-2). In the AUS group (39 patients), most patients (69%) had an MSIGS 3 or 4 with SCT. Spearman's coefficient between quantification of SCT and pad weight for the overall group was ρ = .68 (P < .0001) demonstrating a strong positive correlation. PPD was also strongly correlated with pad weight (ρ = .55, P < .0001). As seen previously, SCT and PPD were correlated (ρ = .47, P < .0001). In a multivariable model predicting pad weight, the effect of SCT was greater than PPD (ß = 83 [54-111], P < .0001 vs 45 [2169], P = .0004). CONCLUSIONS: SCT findings strongly correlate to 24-hour pad weights in the evaluation of male SUI. The SCT shows promise as a rapid, reliable, noninvasive measure of SUI severity before anti-incontinence surgery.

Synchronous Urethral Repair During Prosthetic Surgery: Safety of Planned and Damage Control Approaches Using Suprapubic Tube Urinary Diversion.

BACKGROUND: Urethral injury during inflatable penile prosthesis (IPP) or artificial urinary sphincter (AUS) placement is rare, and traditionally most prosthetic surgeons abort prosthetic implantation when urethral repair is necessary. AIM: To report our experience with synchronous urethroplasty (SU) as a planned or damage control surgery during urologic prosthetic surgery, to evaluate the safety and outcomes of the procedure. METHODS: A retrospective review of our IPP and AUS database was completed to identify patients who underwent an SU between 2007 and 2018. We included patients who underwent an SU during prosthetic surgery in either a planned procedure for known stricture or diverticulum or a "damage control" procedure after intraoperative injury. OUTCOME: Patient characteristics and surgical outcomes were assessed, with success defined as the absence of urethral stricture and revision surgery. RESULTS: From our database of 1,508 prosthetic cases, we identified 7 patients (0.46%) who had an SU in the same setting as complete prosthesis placement (4 AUS and 3 IPP [1 combined IPP/AUS], and 1 sling). Three patients underwent planned repair of a known urethral abnormality (urethral diverticulum, urethrocutaneous fistula, and urethral stricture), and 4 underwent repair of an intraoperative urethral injury. Among the patients who experienced an intraoperative urethral injury, contributing etiologies included previous anti-incontinence surgery with periurethral fibrosis (n = 2), severe corporal fibrosis from priapism, and previous urethral disruption from pelvic fracture. Nearly all of the urethroplasties (6 of 7; 86%) were completed with a primary closure. The average indwelling duration of suprapubic tube (SPT) catheters was 4.1 weeks (range, 7 to 47 days). The average duration of follow-up was 21.5 months, and all patients were continent at follow-up. No device infections or urethral complications were identified. CLINICAL IMPLICATIONS: Our study illustrates the safety of concomitant urethral repair at time of prosthetic placement as an option to avoid the use of 2 anesthetics and prevent further scarring in high-risk patients. STRENGTHS & LIMITATIONS: This is the first study to address definitive urethral reconstruction during anti-incontinence procedures along with planned concomitant urethroplasty during IPP placement. This promising initial experience is relevant for surgeons who may encounter concomitant urethral pathology in the setting of complex reoperative prosthetic cases. The need for SU is rare, and thus our cohort size was limited in this retrospective, single-institution experience. CONCLUSION: SU with prolonged SPT urinary diversion offers a safe damage control approach for men with concomitant urethral pathology during prosthetic surgery without conferring an increased risk of infection or stricture. Yi YA, Fuchs JS, Davenport MT, et al. Synchronous Urethral Repair During Prosthetic Surgery: Safety of Planned and Damage Control Approaches Using Suprapubic Tube Urinary Diversion. J Sex Med 2019;16:1106-1110.

Total Synthesis of Clavatadine B.

The first total synthesis of clavatadine B (2), a natural product found to be a selective human blood coagulation factor XIa inhibitor, is described. A convergent approach that exemplifies the advantages of direct, early stage guanidinylation provided an immediate clavatadine B precursor, which was assembled in an efficient manner using known synthetic precursors of the structurally related natural product clavatadine A (1). Global deprotection cleanly provided clavatadine B in only four steps from a known derivative of homogentisic acid lactone (longest linear sequence, 75% overall yield).

Risk factors for renal cell carcinoma in the VITAL study.

PURPOSE: The incidence of renal cell carcinoma is increasing worldwide. Cited risk factors include obesity, smoking and hypertension but few others have been confirmed in prospective studies. We used a prospective cohort to validate established renal cell carcinoma risk factors and evaluate more controversial risk factors for incident renal cell carcinoma. MATERIALS AND METHODS: A total of 77,260 residents of Washington 50 to 76 years old completed a questionnaire between 2000 and 2002 on demographic, lifestyle and health data. Incident renal cell carcinoma cases were determined by linkage to the regional cancer registry through December 31, 2009. Multivariate methods using covariates and cutoffs selected a priori were applied to analyze the association between renal cell carcinoma and previously studied factors related to lifestyle (body mass index, smoking and alcohol/fruit/vegetable consumption) and health (hypertension, diabetes, kidney disease and viral hepatitis). RESULTS: There were 249 incident cases of renal cell carcinoma. Independent renal cell carcinoma risk factors in the fully adjusted model were body mass index (35 or greater vs less than 25 kg/m2 HR 1.71, 95% CI 1.06-2.79), smoking (greater than 37.5 pack-years vs never HR 1.58, 95% CI 1.09-2.29), hypertension (HR 1.70, 95% CI 1.30-2.22), kidney disease (HR 2.58, 95% CI 1.21-5.50) and viral hepatitis (HR 1.80, 95% CI 1.03-3.14). Diabetes was associated with renal cell carcinoma (HR 1.83, 95% CI 1.26-2.65) in a base model adjusting for age and gender but not in the multivariate model. We found no association between alcohol, fruit or vegetable intake and renal cell carcinoma. CONCLUSIONS: We identified a significant association of renal cell carcinoma with obesity, smoking, hypertension, renal disease and viral hepatitis. Identifying risk factors offers an opportunity for targeted education and intervention.

Antenatally diagnosed hydronephrosis: current postnatal management.

The issue of antenatal hydronephrosis has become a routine component for the care of a pregnant woman despite limited evidence of a clinical benefit. The genitourinary tract represents the most commonly detected organ system with identified abnormalities, with antenatal hydronephrosis (ANH), being the most notable and common finding. ANH represents a spectrum, with most cases being a trivial and inconsequential finding on maternal fetal ultrasound. However, there is a correlation with increased grades of ANH being associated with increased severity of urinary tract pathology. Most patients can be managed expectantly with appropriate evaluation commenced postnatally based on severity of ANH and proper parental counseling and education. The purpose of this review was to assess current literature and guidelines pertaining to ANH and incorporate our practical interpretations of their significance.

Dynamic-dependent selectivity in a bisphosphine iron spin crossover C-H insertion/π-coordination reaction.

Reaction pathway selectivity is generally controlled by competitive transition states. Organometallic reactions are complicated by the possibility that electronic spin state changes rather than transition states can control the relative rates of pathways, which can be modeled as minimum energy crossing points (MECPs). Here we show that in the reaction between bisphosphine Fe and ethylene involving spin state crossover (singlet and triplet spin states) that neither transition states nor MECPs model pathway selectivity consistent with experiment. Instead, single spin state and mixed spin state quasiclassical trajectories demonstrate nonstatistical intermediates and that C-H insertion versus π-coordination pathway selectivity is determined by the dynamic motion during reactive collisions. This example of dynamic-dependent product outcome provides a new selectivity model for organometallic reactions with spin crossover.

Niche-specific contribution to streptococcal virulence of a MalR-regulated carbohydrate binding protein.

Low G+C Gram-positive bacteria typically contain multiple LacI/GalR regulator family members, which often have highly similar amino-terminal DNA binding domains, suggesting significant overlap in target DNA sequences. The LacI/GalR family regulator catabolite control protein A (CcpA) is a global regulator of the Group A Streptococcus (GAS) transcriptome and contributes to GAS virulence in diverse infection sites. Herein, we studied the role of the maltose repressor (MalR), another LacI/GalR family member, in GAS global gene expression and virulence. MalR inactivation reduced GAS colonization of the mouse oropharynx but did not detrimentally affect invasive infection. The MalR transcriptome was limited to only 25 genes, and a highly conserved MalR DNA-binding sequence was identified. Variation of the MalR binding sequence significantly reduced MalR binding in vitro. In contrast, CcpA bound to the same DNA sequences as MalR but tolerated variation in the promoter sequences with minimal change in binding affinity. Inactivation of pulA, a MalR regulated gene which encodes a cell surface carbohydrate binding protein, significantly reduced GAS human epithelial cell adhesion and mouse oropharyngeal colonization but did not affect GAS invasive disease. These data delineate a molecular mechanism by which hierarchical regulation of carbon source utilization influences bacterial pathogenesis in a site-specific fashion.

A direct link between carbohydrate utilization and virulence in the major human pathogen group A Streptococcus.

Although central to pathogenesis, the molecular mechanisms used by microbes to regulate virulence factor production in specific environments during host-pathogen interaction are poorly defined. Several recent ex vivo and in vivo studies have found that the level of group A Streptococcus (GAS) virulence factor gene transcripts is temporally related to altered expression of genes encoding carbohydrate utilization proteins. These findings stimulated us to analyze the role in pathogenesis of catabolite control protein A (CcpA), a GAS ortholog of a key global regulator of carbohydrate metabolism in Bacillus subtilis. Inasmuch as the genomewide effects of CcpA in a human pathogen are unknown, we analyzed the transcriptome of a DeltaccpA isogenic mutant strain grown in nutrient-rich medium. CcpA influences the transcript levels of many carbohydrate utilization genes and several well characterized GAS virulence factors, including the potent cytolysin streptolysin S. Compared with the wild-type parental strain, the DeltaccpA isogenic mutant strain was significantly less virulent in a mouse model of invasive infection. Moreover, the isogenic mutant strain was significantly impaired in ability to colonize the mouse oropharynx. When grown in human saliva, a nutrient-limited environment, CcpA influenced production of several key virulence factors not influenced during growth in nutrient-rich medium. Purified recombinant CcpA bound to the promoter region of the gene encoding streptolysin S. Our discovery that GAS virulence and complex carbohydrate utilization are directly linked through CcpA provides enhanced understanding of a mechanism used by a Gram-positive pathogen to modulate virulence factor production in specific environments.

Contribution of AmyA, an extracellular alpha-glucan degrading enzyme, to group A streptococcal host-pathogen interaction.

alpha-Glucans such as starch and glycogen are abundant in the human oropharynx, the main site of group A Streptococcus (GAS) infection. However, the role in pathogenesis of GAS extracellular alpha-glucan binding and degrading enzymes is unknown. The serotype M1 GAS genome encodes two extracellular proteins putatively involved in alpha-glucan binding and degradation; pulA encodes a cell wall anchored pullulanase and amyA encodes a freely secreted putative cyclomaltodextrin alpha-glucanotransferase. Genetic inactivation of amyA, but not pulA, abolished GAS alpha-glucan degradation. The DeltaamyA strain had a slower rate of translocation across human pharyngeal epithelial cells. Consistent with this finding, the DeltaamyA strain was less virulent following mouse mucosal challenge. Recombinant AmyA degraded alpha-glucans into beta-cyclomaltodextrins that reduced pharyngeal cell transepithelial resistance, providing a physiologic explanation for the observed transepithelial migration phenotype. Higher amyA transcript levels were present in serotype M1 GAS strains causing invasive infection compared with strains causing pharyngitis. GAS proliferation in a defined alpha-glucan-containing medium was dependent on the presence of human salivary alpha-amylase. These data delineate the molecular mechanisms by which alpha-glucan degradation contributes to GAS host-pathogen interaction, including how GAS uses human salivary alpha-amylase for its own metabolic benefit.

Long-term sequelae of inflatable penile prosthesis: clinical characteristics of patients who develop distal cylinder tip extrusion.

BACKGROUND: Impending distal cylinder tip extrusions (DCTE) make up approximately 5-33% of all inflatable penile prosthesis (IPP) reoperations. While there have been a few case reports of DCTE in patients with diabetes and trauma, the current literature regarding risk factors for DCTE is limited. In this study, we examined the long-term sequelae among a large cohort of IPP patients to identify clinical risk factors for impending DCTE. METHODS: A retrospective review was completed of our single surgeon IPP database of 797 IPP placement cases from the years 2007 to 2018. We identified those who had a surgical intervention for a confirmed DCTE. Infected prostheses were excluded. The primary clinical end point of this study was to identify the time to extrusion repair from original penile prosthesis placement. Secondary clinical end points included location of extrusion and presence of corporal fibrosis. RESULTS: Between the years 2007 to 2018, 26 cases (3%) of impending or complete cylinder extrusions were identified in our IPP database (n=797). The mean age at initial IPP placement was 58 years, compared to a mean of 66 years at the time of extrusion. The mean time from initial placement to extrusion repair surgery was 8.4 years (median 5.5 years). Most patients (15/26, 57.7%) had a history of prior IPP placement, five of whom had two or more prior prostheses. Location among the 26 extrusions varied-12 (46.2%) lateral, 9 (34.6%) distal urethra, 2 (7.7%) glanular, 2 (7.7%) mid-shaft, and 1 (3.8%) coronal sulcus. Concomitant pathologies identified include Peyronie's disease (7, 26.9%), idiopathic corporal fibrosis (7, 26.9%) and sickle cell disease with priapism induced erectile dysfunction (3, 11.5%). CONCLUSIONS: The risk of IPP extrusion appears to be associated with increased time from initial prosthesis placement, prior history of IPP placement, and the presence of corporal fibrosis or deformity. Patients should be counseled to recognize this important long-term sequela of IPP surgery.

An update on oxidized regenerated cellulose (fibrillar™) in reducing postoperative corporal bleeding following inflatable penile prosthesis surgery.

BACKGROUND: Scrotal hematoma formation is a dreaded complication of penile prosthesis surgery that increases patient pain and healthcare costs, as well the risk for eventual device infection and failure. The efficacy of hemostatic agents in reducing the incidence of scrotal hematoma development has not been extensively studied in urologic prosthetic surgery. In this paper we further evaluate our experience with oxidized regenerated cellulose (ORC; Surgicel Fibrillar™) as an adjunct to standard hemostatic practices in inflatable penile prosthesis (IPP) implantation. METHODS: From April 2016 onward, intracorporal ORC pledgets were placed during corporotomy closure in all patients undergoing IPP implantation or revision by a single surgeon using an identical surgical technique. Perioperative parameters and outcomes-primarily postoperative cumulative drain output, secondarily patient phone calls in the postoperative period-were compared among successive cases with ORC (April 2016 to February 2019) and without ORC (April 2013 to March 2016). RESULTS: A total of 274 men underwent IPP implantation during the study period; 175 (64%) had ORC included in their corporotomy closures. Median drain output was significantly reduced in the ORC patients relative to the non-ORC group (50 vs. 65 mL; P=0.0001). A significant reduction in patient-initiated phone calls regarding scrotal pain, swelling, or discomfort in the first 4 weeks following surgery was also observed in the ORC group (average 0.69 vs. 1.1 calls per patient; P=0.03). A total of 9 patients underwent IPP explantation during the study period, all due to device infection; 5 of these were in the ORC group, while 4 were in the non-ORC group (P=0.73). ORC use did not constitute any additional infection risk. CONCLUSIONS: Bilateral incorporation of ORC pledgets during corporotomy closure in IPP surgery significantly decreases postoperative scrotal drain output, a well-documented risk factor for scrotal hematoma formation.

Urethral atrophy is now a rare cause for artificial urinary sphincter revision surgery in the contemporary 3.5 cm cuff era.

BACKGROUND: Urethral atrophy has long been suggested as the leading cause of artificial urinary sphincter (AUS) revision. Since the introduction of the 3.5 cm AUS cuff in 2010, precise cuff sizing primarily has been suggested to reduce revisions due to urethral atrophy. We evaluated a large contemporary series of reoperative AUS cases to determine reasons for revision surgery. METHODS: We retrospectively reviewed our tertiary referral center database of male AUS procedures performed by a single surgeon from 2007-2019. AUS revision or replacement procedures were included for analysis. Cuff sizes and reasons for reoperation were recorded based on intraoperative findings and evaluated for temporal trends. Patients with cuff erosion or lacking follow-up were excluded. RESULTS: Among 714 AUS cases, 177 revisions or replacements were identified. Of these, 137 met inclusion criteria [mean age 71.7 years, median follow-up 52.7 months (IQR 22.3-94.6 months)]. Urethral atrophy was cited as the cause of AUS failure in 8.0% (11/137) of cases overall, virtually never among those with a 3.5 cm cuff placement (1/51, 2.0%). In those with ≥4.0 cm cuffs, urethral atrophy was the reason for revision in 10/86 (11.6%). Pressure regulating balloon (PRB) failure was the most frequently cited cause of failure (47/137, 34.3%). Cuff-related failure (23/137, 16.8%) and mechanical failure of unspecified device component (16/137, 11.8%) were the next most frequent causes of failure. CONCLUSIONS: Urethral atrophy has become a rare cause of AUS revision surgery since the availability of smaller cuffs. PRB-related failure is now the leading cause of AUS reoperation.

Preventing the need for revision surgery after penile plication reconstruction of Peyronie's deformities.

BACKGROUND: The need for repeat penile plication (PP) for persistent penile deformity has previously been associated with (I) poor initial erectile response to intracavernosal injection (ICI), (II) an inadequate number of corrective sutures, and (III) a lack of sutures along the proximal shaft of the penis. We present our current experience with PP after implementing corrective measures to assess whether our need for revision surgery was reduced. METHODS: We performed a retrospective review of patients who underwent PP for Peyronie's disease (PD) between 2009-2018 and had a minimum follow-up of 6 months. We updated our surgical technique in 2016 by (I) using supplemental intracorporal saline injections if the initial erection response to prostaglandin E1 injection was inadequate, (II) increasing numbers of corrective plication sutures, and (III) emphasizing more proximal suture placement. Patients were stratified into two groups and outcomes compared (prior technique versus current technique). RESULTS: Of 472 PP patients who met inclusion criteria, 340 (72%) plication patients before 2016 were compared to 132 (28%) performed after 2016. The revision rate in the current cohort (1.5%, 2/132) decreased by more than half compared to the previous cohort (3.8%, 13/340). Mean preoperative angle of curvature was similar between the two groups (50.4 vs. 51.4 degrees, P=0.64), while the average residual postoperative degree was smaller in the current group (7.36 vs. 2.14 degrees, P<0.001). Fewer sutures were used in the early cohort than in the current (7.63 vs. 8.38, P=0.04). After revision, all cases were functionally straight, with a mean postoperative curvature of 4 degrees at a median follow-up of 10.6 months (IQR, 2.08-20.7). CONCLUSIONS: Ensuring adequate rigidity with additional ICI and focusing a greater number of corrective sutures in a more proximal location appears to help prevent the need for revision plication surgery.