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.

HIV Prevalence and HIV Screening History Among a Veterans Association Cohort of People with Opioid and Alcohol Use Disorders.

BACKGROUND: Veterans face high risk for HIV and substance use, and thus could be disproportionately impacted by the HIV and substance use disorder (SUD) "syndemic." HIV prevalence among veterans with SUD is unknown. OBJECTIVE: To project HIV prevalence and lifetime HIV screening history among US veterans with alcohol use disorder (AUD), opioid use disorder (OUD), or both. DESIGN: We conducted a retrospective cohort analysis using national Veterans Health Administration (VHA) data. PARTICIPANTS: We selected three cohorts of veterans with SUD: (1) AUD, (2) OUD, and (3) AUD/OUD. Included veterans had ICD codes for AUD/OUD from 2016 to 2022 recorded in VHA electronic medical records, sourced from the VA Corporate Data Warehouse (CDW). MAIN MEASURES: We estimated HIV prevalence by dividing the number of veterans who met two out of three criteria (codes for HIV diagnosis, antiretroviral therapy, or HIV screening/monitoring) by the total number of veterans in each cohort. We also estimated lifetime HIV screening history (as documented in VHA data) by cohort. We reported HIV prevalence and screening history by cohort and across demographic/clinical subgroups. KEY RESULTS: Our sample included 669,595 veterans with AUD, 63,787 with OUD, and 57,015 with AUD/OUD. HIV prevalence was highest in the AUD/OUD cohort (3.9%), followed by the OUD (2.1%) and AUD (1.1%) cohorts. Veterans of Black race and Hispanic/Latinx ethnicity, with HCV diagnoses, and aged 50-64 had the highest HIV prevalence in all cohorts. Overall, 12.8%, 29.1%, and 33.1% of the AUD/OUD, OUD, and AUD cohorts did not have history of HIV screening, respectively. CONCLUSIONS: HIV prevalence was high in all SUD cohorts, and was highest among veterans with AUD/OUD, with disparities by race/ethnicity and age. A substantial portion of veterans had not received HIV screening in the VHA. Findings highlight room for improvement in HIV prevention and screening services for veterans with SUD.

Gender differences in receipt of telehealth versus in person behavioral therapy, medication for opioid use disorder (MOUD), and 90-day MOUD retention during the pandemic: A retrospective veteran cohort study.

BACKGROUND: COVID-19 significantly negatively impacted access to care among patients with opioid use disorder (OUD). The Veterans Health Administration (VHA) enacted policies to expand telehealth and medication for OUD (MOUD) during the public health emergency, which offset risk of treatment disruption. In this study, we evaluated gender differences in utilization of behavioral therapy in person and via telehealth, MOUD utilization, and achieving 90-day MOUD retention pre-post pandemic onset, given known gender differences in treatment utilization between men and women. Secondarily, we examined MOUD receipt and retention as a function of in-person vs. telehealth behavioral therapy received over time. METHODS: Using VHA's nationwide electronic health record data, we compared outcomes between men and women veterans, pre- to post-pandemic onset (January 2019-February 2020 vs. March 2020-April 2021). Primary outcomes included receipt of behavioral therapy (in person or telehealth), number of appointments attended, any MOUD, and whether patients achieved 90-day MOUD retention post-induction. RESULTS: Veterans with OUD were less likely to receive behavioral therapy post-pandemic onset, which was driven by marked decreases in in-person care; these effects were strongest among women. The odds of receiving MOUD also decreased pre- to post-pandemic onset, particularly among men. Receipt of or achieving 90-day MOUD retention was differentially related to receipt of behavioral therapy via in person vs. telehealth; telehealth was more strongly associated with these utilization indicators post-pandemic onset-an effect that was more pronounced for men. CONCLUSION: The likelihood of receiving behavioral therapy and MOUD were lower during COVID-19 and varied by gender, with men being less likely to receive MOUD over time and women being less likely to receive in-person behavioral therapy. Behavioral therapy received via telehealth was generally associated with improved MOUD utilization compared to in-person behavioral therapy, but this was less true for women than for men regarding utilization of or achieving 90-day MOUD retention. In addition to the need for further telehealth expansion for veterans with OUD, more research should explore how to better engage men in MOUD treatment and improve adherence to MOUD among women engaged in behavioral therapy.

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.

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.

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.

The impact of COVID-19 and rapid policy exemptions expanding on access to medication for opioid use disorder (MOUD): A nationwide Veterans Health Administration cohort study.

BACKGROUND: In March 2020, Veterans Health Administration (VHA) enacted policies to expand treatment for Veterans with opioid use disorder (OUD) during COVID-19. In this study, we evaluate whether COVID-19 and subsequent OUD treatment policies impacted receipt of therapy/counseling and medication for OUD (MOUD). METHODS: Using VHA's nationwide electronic health record data, we compared outcomes between a comparison cohort derived using data from prior to COVID-19 (October 2017-December 2019) and a pandemic-exposed cohort (January 2019-March 2021). Primary outcomes included receipt of therapy/counseling or any MOUD (any/none); secondary outcomes included the number of therapy/counseling sessions attended, and the average percentage of days covered (PDC) by, and months prescribed, each MOUD in a year. RESULTS: Veterans were less likely to receive therapy/counseling over time, especially post-pandemic onset, and despite substantial increases in teletherapy. The likelihood of receiving buprenorphine, methadone, and naltrexone was reduced post-pandemic onset. PDC on MOUD generally decreased over time, especially methadone PDC post-pandemic onset, whereas buprenorphine PDC was less impacted during COVID-19. The number of months prescribed methadone and buprenorphine represented relative improvements compared to prior years. We observed important disparities across Veteran demographics. CONCLUSION: Receipt of treatment was negatively impacted during the pandemic. However, there was some evidence that coverage on methadone and buprenorphine may have improved among some veterans who received them. These medication effects are consistent with expected COVID-19 treatment disruptions, while improvements regarding access to therapy/counseling via telehealth, as well as coverage on MOUD during the pandemic, are consistent with the aims of MOUD policy exemptions.

Age ≤40 is an independent predictor of anastomotic urethroplasty and successful repair of bulbar urethral strictures.

BACKGROUND: Among men with bulbar strictures, we aimed to analyze stricture characteristics, repair type, and treatment success in younger versus older patient cohorts. METHODS: We retrospectively reviewed our single surgeon database with patients undergoing bulbar urethroplasty from 2007 to 2017. This population was then age-stratified into ≤40 and >40-year-old cohorts. Exclusion criteria included patients with penile strictures and those with history of hypospadias. Patient characteristics, surgical approach, and outcome were compiled by medical record and database review. Criterion for success included functional emptying and lack of repeat surgical intervention. Parameters associated with failure were included in multivariate logistic regression models. RESULTS: Eight hundred and fifty-three patients with bulbar strictures were identified, 231 patients (27.1%) ≤40 years old and 622 patients (72.9%) >40 years old. Mean stricture length was significantly longer in older men (2.3 vs. 2.7 cm, P=0.005). Excision and primary anastomosis (EPA) were more commonly utilized when managing younger compared to older patient groups (87% in ≤40 group, 77% in >40, P=0.0009). Younger men underwent significantly fewer endoscopic stricture treatments than older men (2.1 vs. 4.9, P=0.001). Traumatic etiology was more commonly attributable in the younger group (48% vs.17%, P<0.0001). Younger men presented less frequently with diabetes (1.7% vs. 21.7%, P<0.0001), coronary artery disease (0.4% vs. 19.1%, P<0.0001), and erectile dysfunction (11.5% vs. 29.2%, P<0.0001) relative to older men. Over a median follow-up of 52.4 months, success rates were higher in the ≤40 cohort (97.4%) than the >40 cohort (87.3%, P<0.0001). On multivariate logistic regression, independent predictors of urethroplasty success include younger age), utilization of EPA, and lack of pelvic radiation. CONCLUSIONS: Although men ≤40 years old have a higher incidence of traumatic etiology, bulbar urethroplasty has a higher success rate when compared to patients >40 years old. Bulbar strictures are more amenable to EPA in the younger population, likely due to fewer endoscopic treatments and favorable tissue characteristics.

Outpatient buccal mucosal graft urethroplasty outcomes are comparable to inpatient procedures.

BACKGROUND: We sought to compare outcomes between inpatient and outpatient buccal mucosal graft (BMG) urethroplasty among a large tertiary referral center series. METHODS: A retrospective review of consecutive patients who underwent BMG urethroplasty between 2007 and 2018 was performed, including only first stage and one stage graft procedures. Patients were divided into inpatient and outpatient groups. Demographic and outcome data were collected and analyzed, with success defined as no need for further endoscopic or open reoperative management. RESULTS: Of 143 patients undergoing BMG urethroplasty during the study period, 87 cases (60.8%) were performed on an inpatient basis, and 56 (39.2%) on an outpatient basis. Patient characteristics such as age, BMI, prior endoscopic procedures and co-morbid factors were similar between inpatient and outpatient groups. Perioperative characteristics such as estimated blood loss were also similar between groups, but the inpatient cohort had a longer operative time (157.6 vs. 123.1 min, P<0.0001). Operative success was comparable in the two groups (74.7% inpatient vs. 76.8% outpatient, P=0.7) as were rates of complications (29.9% inpatient vs. 26.8% outpatient, P=0.07). CONCLUSIONS: BMG urethroplasty can be safely performed in an ambulatory setting without increased complications or compromised outcomes.

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.

Comparison of 3.5 cm and transcorporal cuffs in high-risk artificial urinary sphincter populations.

BACKGROUND: The transcorporal (TC) artificial urinary sphincter (AUS) has traditionally been utilized in high-risk patients with urethral atrophy or prior urethral erosion. The 3.5 cm AUS cuff has been developed for use in a similar population. We compared the outcomes of TC AUS and 3.5 cm cuff patients to assess whether the TC approach was protective against urethral complications. METHODS: We performed a retrospective review for all men who underwent TC AUS and 3.5 cm AUS implantation by a single surgeon from 2007 to 2018 at a tertiary medical center. Demographic and outcomes data were collected and analyzed after database review to evaluate for rates of urethral erosion. Multivariate logistic regression was performed to identify co-morbid factors associated with urethral erosion. RESULTS: In our database of 625 AUS patients, we identified 59 (9%) men with TC AUS and 168 (27%) having a 3.5 cm cuff. Over a median follow-up time of 49 months, 28 (47%) men with TC cuffs developed urethral erosion compared with 25 (15%) men with a 3.5 cm cuff. On univariate analysis, a TC cuff was associated with increased odds of erosion (OR 6.65, 95% CI: 3.20-14.4, P<0.0001) when compared with a 3.5 cm cuff. On multivariate analysis, TC cuffs continued to portend significantly increased odds of cuff erosion. CONCLUSIONS: With longer follow up, TC AUS may not be as protective against urethral complications as previously described.

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.

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.

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.

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).

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.