De Novo Synthesis of Perdeuterated Phosphoinositide by Installing a Non-native Phospholipid Biopathway in E. coli.

Phosphatidylinositol (PI) and its phosphorylated derivatives are of paramount importance in cellular functions and diseases. Understanding their diverse roles is, however, challenged by difficulties in synthesis and labeling techniques. In this proof-of-concept study, we demonstrate that PI can be straightforwardly de novo-synthesized and deuterium (2H)-labeled in Escherichia coli by genomic insertion of PI synthase from Trypanosoma brucei under constitutive synthetic promoter proD. Insertion into loci atpi-gidB and ybb revealed PI accumulation of 41% and 34% (mol/mol), respectively, when cultivated with glycerol as the sole carbon source. Growth of the atpi-gidB-PIS strain in deuterium-labeled (2H) substrates D2O, D8-glycerol, and D6-myo-inositol achieved PI deuteration of 90%, PE deuteration of 95%, and total fatty acids|fatty acid (FA) deuteration of 97%. This study offers an alternative convenient route to chemical and enzymatic labeling synthesis of PI; more excitingly, this work also, in principle, opens a door for tailoring the FA profile of deuterated PI/PE for task-specific application by repurposing FA biosynthesis pathways.

Implementation and Interim Analysis of a Standardized Renal Trauma Imaging and Urinary Extravasation Management Protocol.

INTRODUCTION: The AUA recommends delayed-phase imaging (DPI) in renal injuries to evaluate the collecting system. A renal trauma imaging protocol for early conservative management of urinary extravasation (UE) was implemented to improve guideline adherence. We aimed to determine if increased adherence led to changes in outcomes. METHODS: Patients with American Association for the Surgery of Trauma III to V renal injury presenting from January 2018 to September 2022 were identified from an institutional trauma registry. Patients were included if a contrasted CT scan of the abdomen was obtained on admission. Frequency of DPI and patient outcomes were compared before and after protocol implementation. RESULTS: Of 223 included patients, 131 (58.7%) were pre protocol and 92 (41.3%) were post protocol. Following protocol implementation, the rate of DPI on admission nearly doubled from 32.8% to 58.7% (P < .001). The rate of follow-up cross-sectional imaging increased from 18.3% to 58.7% (P < .001). Although there were no significant differences in rates of immediate or delayed interventions following protocol implementation, the postprotocol immediate intervention rate did decrease to 0%. Readmissions due to symptomatic UE were unchanged after protocol implementation (0.0% vs 0.0%). CONCLUSIONS: Implementation of a multidisciplinary renal trauma early imaging and management protocol improved AUA guideline adherence. With protocol adherence, there was also an elimination of immediate interventions for UE. Despite decreases in early intervention, there was no significant increase in interval interventions or UE-related readmissions. More research is needed to determine the role for routine follow-up imaging in conservative management of high-grade renal trauma.

Early Post-Operative Events After Urethroplasty in Obese Patients: A Multi-Institutional Retrospective Series.

OBJECTIVE: To compare early urethroplasty outcomes in non-obese, obese and morbidly obese patients undergoing urethroplasty for urethral stricture disease. The impact of obesity on outcomes is poorly understood but will be increasingly important as obesity continues to rise. METHODS: Patients underwent urethroplasty at one of the 5 institutions between January 2016 and December 2020. Obese (BMI 30-39.9, n = 72) and morbidly obese (BMI >40, n = 49) patients were compared to normal weight (BMI <25, n = 29) and overweight (BMI 25-29.9, n = 51) patients. Demographics, comorbidities, and stricture characteristics were collected. Outcomes including complications, recurrence, and secondary interventions were compared using univariate and multivariate analysis. RESULTS: Two hundred and one patients (Mean BMI 34.1, Range 18.4-65.2) with mean age 52.2 years (SD=17.2) were analyzed. Median follow-up time was 3.71 months. Obese patients were younger (P = .008), had more anterior (P <.001), iatrogenic and LS-associated strictures (P = .036). Sixty-day complication rate was 26.3% with no differences between cohorts (P = .788). Around 9.5% of patients had extravasation at catheter removal, 18.9% reported stricture recurrence, and 7.4% required additional interventions. Obese patients had greater estimated blood loss (P = .001) and length of stay (P = .001). On multivariate analysis, smoking associated with contrast leak (OR 7.176, 95% CI 1.13-45.5) but not recurrence or need for intervention (P = .155, .927). CONCLUSION: Obese patients in our cohort had more anterior, iatrogenic, and LS-related strictures. However, obesity is not associated with complications, contrast leak, secondary interventions, or recurrence. Obese had higher blood loss and length of stay. Urethroplasty is safe and effective in obese patients.

Impact of sexual function domains on sexual satisfaction and quality of life: Importance across the age spectrum.

BACKGROUND: Sexual satisfaction is an important component of global quality life for many adult men. Substantial gaps exist in our appreciation of how age mediates sexual satisfaction in the context of functional sexual measures. We sought to evaluate modifiable factors associated with overall sexual satisfaction and health-related quality of life (HRQoL) in a large, age-stratified community-based sample of adult men. METHODS: A sample of adult males registered with the online research service ResearchMatch completed a 75-item online questionnaire in this cross-sectional study. Queries included demographics, general health data, and validated sexual health measures including International Index of Erectile Function-5 (IIEF-5) and Premature Ejaculation Diagnostic Tool (PEDT). Multivariable regression was performed to assess associations with self-reported sexual satisfaction (defined by "moderately satisfied" or "very satisfied" on the 5-level Likert scale) and overall HRQoL (as measured by the EQ-5D-visual analog scale (VAS) stratified by age. RESULTS: One thousand thirty-three men completed the survey and were stratified by age cohorts. IIEF-5 and PEDT scores were higher in younger cohorts. On multivariable regression analysis, higher IIEF-5, lower PEDT, better overall health-related quality of life, and the presence of a sexual partner within the last month were associated with an increased likelihood of overall sexual satisfaction. When stratified by age cohort, higher IIEF-5 scores were consistently positively associated with sexual satisfaction (Odds Ratio (OR) 1.18, 95% CI 1.15-1.22, P < 0.001), as well as independently associated with improved overall HRQoL by EQ-5D-VAS (ß = 0.71, Standard Error (SE) = 0.08, P < 0.001). CONCLUSIONS: The erectile function was independently associated with sexual satisfaction and quality of life across all age strata and predictive of both sexual satisfaction and global HRQoL. Low overall rates of sexual satisfaction across cohorts highlight the critical importance of evaluation and treatment of sexual health, regardless of age.

Qualitative Analysis of Patient Experiences Reaching Urethroplasty for Recurrent Urethral Stricture Disease.

PURPOSE: Despite the inferior outcomes, urethral stricture patients often undergo multiple endoscopic procedures prior to undergoing definitive urethroplasty. We sought to qualitatively evaluate the patient experience of obtaining urethroplasty to better understand the impact of this experience on quality of life. MATERIALS AND METHODS: Patients treated with urethroplasty between September 2019 and July 2021 were identified and invited to participate in our study if they had undergone ≥ 2 endoscopic procedures prior to urethroplasty. Semistructured telephone interviews were conducted, coded, and analyzed using an iterative inductive-deductive approach. RESULTS: Of the 105 urethroplasty patients during the study period, 50 (47.6%) had undergone ≥ 2 endoscopic procedures prior (IQR 3-5), of whom 20 participated in the study. Qualitative themes related to repeat endoscopic procedures included unmet treatment expectations, dissatisfaction with catheterization and repeat procedures, and negative impacts of recurrent stricture symptoms and treatments on quality of life. External factors associated with a delay to urethroplasty included financial constraints, surgeon access, and time off work. CONCLUSIONS: A trajectory of declining quality of life and unmet treatment expectations are the primary factors driving the decision to proceed with urethroplasty. However, external factors such as recovery costs and access to specialists play important roles in delaying surgery. These findings illustrate the need for improved community provider education and patient counseling to better inform expectations of both patients and providers with various treatment outcomes. Furthermore, these data highlight the need to improve access to specialized care for urethral stricture patients.

Current opinions on the management of prolonged ischemic priapism: does penoscrotal decompression outperform corporoglanular tunneling?

Prolonged ischemic priapism presents a treatment challenge given the difficulty in achieving detumescence and effects on sexual function. To evaluate current practice patterns, an open, web-based multi-institutional survey querying surgeons' experience with and perceived efficacy of tunneling maneuvers (corporoglanular tunneling and penoscrotal decompression), as well as impressions of erectile recovery, was administered to members of societies specializing in male genital surgery. Following distribution, 141 responses were received. Tunneling procedures were the favored first-line surgical intervention in the prolonged setting (99/139, 71.2% tunneling vs. 14/139, 10.1% implant, p < .001). Although respondents were more likely to have performed corporoglanular tunneling than penoscrotal decompression (124/138, 89.9% vs. 86/137, 62.8%, p < .001), penoscrotal decompression was perceived as more effective among those who had performed both (47.3% Very or Extremely Effective for penoscrotal decompression vs. 18.7% for corporoglanular tunneling; p < .001). Many respondents who had performed both tunneling procedures felt that most regained meaningful sexual function after either corporoglanular tunneling or penoscrotal decompression (33/75, 44.0% vs. 33/74, 44.6%, p = .942). While further patient-centered investigation is warranted, this study suggests that penoscrotal decompression may outperform corporoglanular tunneling for prolonged priapism, and that recovery of sexual function may be higher than previously thought after tunneling procedures.

A Chemo-Enzymatic Cascade Strategy for the Synthesis of Phosphatidylcholine Incorporated with Structurally Diverse FAHFAs.

Fatty acid esters of hydroxy fatty acids (FAHFAs), a newly discovered class of human endogenous complex lipids showing great promise for treating diabetes and inflammatory diseases, exist naturally in extremely low concentrations. This work reports a chemo-enzymatic approach for the comprehensive synthesis of phospholipids containing FAHFAs via sequential steps: hydratase-catalyzed hydration of unsaturated fatty acids to generate structurally diverse hydroxy fatty acids (HFAs), followed by the selective esterification of these HFAs with fatty acids mediated by secondary alcohol-specific Candida antarctica lipase A (CALA), resulting in the formation of a series of diverse FAHFA analogs. The final synthesis is completed through carbodiimide-based coupling of FAHFAs with glycerophosphatidylcholine. Optimal reaction conditions are identified for each step, and the substrate affinity of CALA, responsible for the catalytic mechanisms during FAHFA production, is evaluated through molecular docking. Compared to multistep lab-tedious chemical synthesis, this route, relying on natural building blocks and natural biocatalysts, is significantly facile, scalable, and highly selective, affording high yields (74-98 mol %) in each step for the construction of higher FAHFA-PC series (10/12/13-FAHFAs). The developed strategy aims to increase the availability of naturally occurring FAHFA species and provide the tools for the construction of versatile and novel analogs of FAHFA conjugates.

Erectile dysfunction after acetabular fracture.

Objectives: To determine the rate of erectile dysfunction in male patients who have sustained an acetabular fracture with no previously identified urogenital injury. Design: Cross-sectional survey. Setting: Level 1 Trauma Center. Patients/Participants: All male patients treated for acetabular fracture without urogenital injury. Intervention: The International Index of Erectile Function (IIEF), a validated patient-reported outcome measure for male sexual function, was administered to all patients. Main Outcome Measurements: Patients were asked to complete the International Index of Erectile Function score for both preinjury and current sexual function, and the erectile function (EF) domain was used to quantify the degree of erectile dysfunction. Fractures were classified according the OTA/AO classification schema, fracture classification, injury severity score, race, and treatment details, including surgical approach were collected from the database. Results: Ninety-two men with acetabular fractures without previously diagnosed urogenital injury responded to the survey at a minimum of 12 months and an average of 43 ± 21 months postinjury. The mean age was 53 ± 15 years. 39.8% of patients developed moderate-to-severe erectile dysfunction after injury. The mean EF domain score decreased 5.02 ± 1.73 points, which is greater than the minimum clinically important difference of 4. Increased injury severity score and associated fracture pattern were predictive of decreased EF score. Conclusion: Patients with acetabular fractures have an increased rate of erectile dysfunction at intermediate-term follow-up. The orthopaedic trauma surgeon treating these injuries should be aware of this as a potential associated injury, ask their patients about their function, and make appropriate referrals. Level of Evidence: III.

A Disease-Specific Antibiogram to Evaluate Empiric Coverage Patterns in Fournier's Gangrene.

OBJECTIVE: To analyze our local antibiogram and antibiotic resistance patterns given concern for multidrug-resistant and fungal organisms in contemporary series detailing causative organisms in Fournier's Gangrene (FG). METHODS: All patients from 2018 to 2022 were identified from the institutional FG registry. Microorganisms and sensitivities were collected from operative tissue cultures. The primary outcome of this study was the adequacy of our empiric. Secondary outcomes included the rate of bacteremia, the concordance of blood cultures and tissue cultures, and the rate of fungal tissue infections. RESULTS: Escherichia coli and Streptococcus anginosus were most common, identified in 12 patients each (20.0%). Enterococcus faecalis (9, 15.0%), S agalactiae (8, 13.3%) and mixed cultures without a predominant organism (9, 15.0%) were also common. A fungal organism was identified in 9 (15.0%) patients. Patients who were started on Infectious Diseases Society of America guideline adherent antibiotic regimen were not significantly different in terms of bacteremia rate (P = .86), mortality (P = .25), length of stay (P = .27), or final antibiotic duration (P = .43) when compared to those on alternative regimens. Patients with a tissue culture positive for a fungal organism were not significantly different in terms of Fournier's Gangrene Severity Index (P = .25) or length of stay (P = .19). CONCLUSION: Local disease-specific antibiograms can be a powerful tool to guide empiric antibiotic therapy in FG. Although fungal infections are responsible for a majority of the gaps in empiric antimicrobial coverage at our institution they were present in only 15% of patients and their effect on outcomes does not justify addition of empiric antifungal agents.

Implementation of a comprehensive prehabilitation program for patients undergoing radical cystectomy.

BACKGROUND: Coordinated preoperative optimization programs for radical cystectomy (RC) are limited and non-comprehensive. We evaluated the feasibility and acceptability of a coordinated, multi-faceted prehabilitation program for RC patients at a high-volume bladder cancer referral center. METHODS: We performed a narrative literature review for prehabilitation in bladder cancer management as of December 1, 2020, with specific emphasis on examining higher-level evidence sources. We selected domains with the highest level of evidence and recruited a multidisciplinary team of experts to design our program. We implemented a comprehensive prehabilitation program with a pre-defined order set as standard of care for all patients undergoing RC beginning February 1, 2021. Demographic and clinicopathologic data were collected prospectively. Rates of adherence to the prehabilitation program services were analyzed using Stata version 13. RESULTS: A total of 82 patients were enrolled between February - December 2021, of which 67 (81%) had undergone RC at data cutoff. Mean age was 68 years (SD 11) and 63 (76%) identified as male. Neoadjuvant chemotherapy (NAC) was utilized in 48 (59%) patients. The mean Charlson Comorbidity Index was 3.8 (SD 2.3). 100% of patients were screened for malnutrition, with 82% consuming nutritional supplements. Fifty-two percent of patients attended physical therapy pre-op. The 30-day and 30- to 90-day rates of complications were 56% and 40%, respectively. Resource length of stay (RLOS) declined after implementation of prehabilitation. CONCLUSIONS: Implementation of a comprehensive prehabilitation program at a high-volume bladder cancer referral center is feasible and has a modest effect on resource consumption and complications in our early experience.

A multicenter prospective cohort study of endoscopic urethral realignment versus suprapubic cystostomy after complete pelvic fracture urethral injury.

BACKGROUND: Pelvic fracture urethral injury (PFUI) occurs in up to 10% of pelvic fractures. There is mixed evidence supporting early endoscopic urethral realignment (EUR) over suprapubic tube (SPT) placement and delayed urethroplasty. Some studies show decreased urethral obstruction with EUR, while others show few differences. We hypothesized that EUR would reduce the rate of urethral obstruction after PFUI. METHODS: Twenty-six US medical centers contributed patients following either an EUR or SPT protocol from 2015 to 2020. If retrograde cystoscopic catheter placement failed, patients were included and underwent either EUR or SPT placement based on their institution's assigned treatment arm. Endoscopic urethral realignment involved simultaneous antegrade/retrograde cystoscopy to place a catheter across the urethral injury. The primary endpoint was development of urethral obstruction. Fisher's exact test was used to analyze the relationship between PFUI management and development of urethral obstruction. RESULTS: There were 106 patients with PFUI; 69 (65%) had complete urethral disruption and failure of catheter placement with retrograde cystoscopy. Of the 69 patients, there were 37 (54%) and 32 (46%) in the EUR and SPT arms, respectively. Mean age was 37.0 years (SD, 16.3 years) years, and mean follow-up was 463 days (SD, 280 days) from injury. In the EUR arm, 36 patients (97%) developed urethral obstruction compared with 30 patients (94%) in the SPT arm ( p = 0.471). Urethroplasty was performed in 31 (87%) and 29 patients (91%) in the EUR and SPT arms, respectively ( p = 0.784). CONCLUSION: In this prospective multi-institutional study of PFUI, EUR was not associated with a lower rate of urethral obstruction or need for urethroplasty when compared with SPT placement. Given the potential risk of EUR worsening injuries, clinicians should consider SPT placement as initial treatment for PFUI when simple retrograde cystoscopy is not successful in placement of a urethral catheter. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Sexual Dysfunction in Women after Traumatic Pelvic Fracture Negatively Affects Quality of Life and Mental Health.

BACKGROUND: While the impact of female sexual dysfunction (FSD) on mental health and overall health-related quality of life (HrQOL) has been previously documented, no prior work has evaluated this relationship in women following traumatic pelvic injuries. AIM: This study aims to understand the relationship of FSD with HrQOL and depression in women with a history of traumatic pelvic fracture. METHODS: Data were collected with an electronic survey that included queries regarding mental and sexual health. Inverse probability weighting and multivariate regression models were utilized to assess the relationships between sexual dysfunction, depression and HrQOL. OUTCOMES: Study outcome measures included the Female Sexual Function Index (FSFI) to evaluate sexual functioning, the 8-item patient health questionnaire (PHQ-8) to assess depression symptoms, and the visual analog scale (VAS) component of the EuroQol 5 Dimensions Questionnaire (EQ-5D) to determine self-reported HrQOL. RESULTS: Women reporting FSD had significantly higher PHQ-8 scores with a median PHQ-8 score of 6 (IQR 2, 11) relative to those without FSD who had a median score of 2 (IQR 0, 2) (P < .001). On multivariate linear regression, presence of FSD was significantly associated with higher PHQ-8 scores (ß = 4.91, 95% CI 2.8-7.0, P < .001). FSFI score, time from injury, and age were all independently associated with improved HrQOL, with FSFI having the largest effect size (ß = 0.62, 95% CI 0.30-0.95, P < .001). CLINICAL IMPLICATIONS: These results underscore importance of addressing not just sexual health, but also mental health in female pelvic fracture survivors in the post-injury setting. STRENGTHS AND LIMITATIONS: This study is one of the first to examine women with traumatic pelvic fractures who did not sustain concomitant urinary tract injuries. Study limitations include low response rate and the inherent limitations of a cross-sectional study design. CONCLUSION: Patients with persistent, unaddressed FSD after pelvic fracture are at unique risk for experiencing depression and reporting worse health-related quality of life due to complex biopsychosocial mechanisms. Gambrah HA, Hagedorn JC, Dmochowski RR, et al. Sexual Dysfunction in Women after Traumatic Pelvic Fracture Negatively Affects Quality of Life and Mental Health. J Sex Med 2022;19:1759-1765.

The Outcomes of Pelvic Fracture Urethral Injuries Stratified by Urethral Injury Severity: A Prospective Multi-institutional Genitourinary Trauma Study (MiGUTS).

OBJECTIVE: To determine patient outcomes across a range of pelvic fracture urethral injury (PFUI) severity. PFUI is a devastating consequence of a pelvic fracture. No study has stratified PFUI outcomes based on severity of the urethral distraction injury. METHODS: Adult male patients with blunt-trauma-related PFUI were followed prospectively for a minimum of six months at 27 US medical centers from 2015-2020. Patients underwent retrograde cystourethroscopy and retrograde urethrography to determine injury severity and were categorized into three groups: (1) major urethral distraction, (2) minor urethral distraction, and (3) partial urethral injury. Major distraction vs minor distraction was determined by the ability to pass a cystoscope retrograde into the bladder. Simple statistics summarized differences between groups. Multi-variable analyses determined odds ratios for obstruction and urethroplasty controlling for urethral injury type, age, and Injury Severity Score. RESULTS: There were 99 patients included, 72(72%) patients had major, 13(13%) had minor, and 14(14%) had partial urethral injuries. The rate of urethral obstruction differed in patients with major (95.8%), minor (84.6%), and partial injuries (50%) (P < 0.001). Urethroplasty was performed in 90% of major, 66.7% of minor, and 35.7% of partial injuries (P < 0.001). CONCLUSION: In PFUI, a spectrum of severity exists that influences outcomes. While major and minor distraction injuries are associated with a higher risk of developing urethral obstruction and need for urethroplasty, up to 50% of partial PFUI will result in obstruction, and as such need to be closely followed.