The Impact of Social Deprivation on Anterior Urethral Stricture Recurrence After Urethroplasty - A Trauma and Urologic Reconstructive Network of Surgeons (TURNS) Analysis.

INTRODUCTION AND OBJECTIVES: Several factors influence recurrence after urethral stricture repair. The impact of socioeconomic factors on stricture recurrence after urethroplasty is poorly understood. This study aims to assess the impact that social deprivation, an area-level measure of disadvantage, has on urethral stricture recurrence after urethroplasty. METHODS: We performed a retrospective review of patients undergoing urethral reconstruction by surgeons participating in a collaborative research group. Home zip code was used to calculate Social Deprivation Indices (SDI; 0-100), which quantifies the level of disadvantage across several sociodemographic domains collected in the American Community Survey. Patients without zip code data were excluded from the analysis. The Cox Proportional Hazards model was used to study the association between SDI and the hazard of functional recurrence, adjusting for stricture characteristics as well as age and body mass index. RESULTS: Median age was 46.0 years with a median follow up of 367 days for the 1452 men included in the study. Patients in the fourth SDI quartile (worst social deprivation) were more likely to be active smokers with traumatic and infectious strictures compared to the first SDI quartile. Patients in the fourth SDI quartile had 1.64 times the unadjusted hazard of functional stricture recurrence vs patients in the first SDI quartile (95% CI 1.04-2.59). Compared to anastomotic ± excision, substitution only repair had 1.90 times the unadjusted hazard of recurrence. The adjusted hazard of recurrence was 1.08 per 10-point increase in SDI (95% CI 1.01-1.15, P = .027). CONCLUSIONS: Patient social deprivation identifies those at higher risk for functional recurrence after anterior urethral stricture repair, offering an opportunity for preoperative counseling and postoperative surveillance. Addressing these social determinants of health can potentially improve outcomes in reconstructive surgery.

Fluorous Liquids for Magnetic Resonance-Based Thermometry with Enhanced Responsiveness and Environmental Degradation.

Accurate temperature measurement via magnetic resonance is valuable for both in vitro and in vivo analysis of local tissue for evaluating disease pathology and medical interventions. 1H MRI-based thermometry is used clinically but is susceptible to error from magnetic field drift and low sensitivity in fatty tissue and requires a reference for absolute temperature determination. As an alternative, perfluorotributylamine (PFTBA), a perfluorocarbon liquid for 19F MRI thermometry, is based on chemical shift responsiveness and approaches the sensitivity of 1H MRI thermometry agents; however, environmental persistence, greenhouse gas concerns, and multiple resonances which can lead to MRI artifacts indicate a need for alternative sensors. Using a 19F NMR-based structure-property study of synthetic organofluorine molecules, this research develops new organofluorine liquids with improved temperature responsiveness, high signal, and reduced nonmagnetically equivalent fluorine resonances. Environmental degradation analysis using reverse-phase HPLC and quantitative 19F NMR demonstrates a rapid degradation profile mediated via the aryl fluorine core of temperature sensors. Our findings show that our lead liquid temperature sensor, DD-1, can be made in high yield in a single step and possesses an improved responsiveness over our prior work and an 83% increase in aqueous thermal responsiveness over PFTBA. Degradation studies indicate robust degradation with half-lives of less than two hours under photolysis conditions for the parent compound and formation of other fluorinated products. The improved performance of DD-1 and its susceptibility to environmental degradation highlight a new lead fluorous liquid for thermometry applications.

Leveraging the HMBC to Facilitate Metabolite Identification.

The accuracy and ease of metabolite assignments from a complex mixture are expected to be facilitated by employing a multispectral approach. The two-dimensional (2D) 1H-13C heteronuclear single quantum coherence (HSQC) and 2D 1H-1H-total correlation spectroscopy (TOCSY) are the experiments commonly used for metabolite assignments. The 2D 1H-13C HSQC-TOCSY and 2D 1H-13C heteronuclear multiple-bond correlation (HMBC) are routinely used by natural products chemists but have seen minimal usage in metabolomics despite the unique information, the nearly complete 1H-1H and 1H-13C and spin systems provided by these experiments that may improve the accuracy and reliability of metabolite assignments. The use of a 13C-labeled feedstock such as glucose is a routine practice in metabolomics to improve sensitivity and to emphasize the detection of specific metabolites but causes severe artifacts and an increase in spectral complexity in the HMBC experiment. To address this issue, the standard HMBC pulse sequence was modified to include carbon decoupling. Nonuniform sampling was also employed for rapid data collection. A dataset of reference 2D 1H-13C HMBC spectra was collected for 94 common metabolites. 13C-13C spin connectivity was then obtained by generating a covariance pseudo-spectrum from the carbon-decoupled HMBC and the 1H-13C HSQC-TOCSY spectra. The resulting 13C-13C pseudo-spectrum provides a connectivity map of the entire carbon backbone that uniquely describes each metabolite and would enable automated metabolite identification.

Urethroscopic Findings following Urethroplasty Predict the Need for Secondary Intervention in the Long Term: A Multi-Institutional Study from Trauma and Urologic Reconstructive Network of Surgeons.

PURPOSE: Postoperative surveillance urethroscopy has been shown to be an effective tool to predict reoperation within 1 year after urethroplasty. We aimed to evaluate early surveillance urethroscopy findings and long-term outcomes among urethroplasty patients in order to define the value of surveillance urethroscopy to predict failure. MATERIALS AND METHODS: We evaluated 304 patients with at least 4 years of followup after urethroplasty performed at 10 institutions across the United States and Canada. All patients were surveilled using a flexible 17Fr cystoscope and were categorized into 3 groups: 1) normal lumen, 2) large-caliber stricture (≥17Fr) defined as the ability of the cystoscope to easily pass the narrowing and 3) small-caliber stricture (<17Fr) that the cystoscope could not be passed. Failure was stricture recurrence requiring a secondary intervention. RESULTS: The median followup time was 64.4 months (range 55.3-80.6) and the time to initial surveillance urethroscopy was 3.7 months (range 3.1-4.8) following urethroplasty. Secondary interventions were performed in 29 of 194 (15%) with normal lumens, 11 of 60 (18.3%) with ≥17Fr strictures and 32 of 50 (64%) with <17Fr strictures (p <0.001). The 1-, 3- and 9-year cumulative probability of intervention was 0.01, 0.06 and 0.23 for normal, 0.05, 0.17 and 0.18 for ≥17Fr, and 0.32, 0.50 and 0.73 for <17Fr lumen groups, respectively. Patient-reported outcome measures performed poorly to differentiate the 3 groups. CONCLUSIONS: Early cystoscopic visualization of scar recurrence that narrows the lumen to <17Fr following urethroplasty is a significant long-term predictor for patients who will eventually undergo a secondary intervention.

Minimizing Antibiotic Use in Urethral Reconstruction.

PURPOSE: There are no established guidelines regarding management of antibiotics for patients specifically undergoing urethral reconstruction. Our aim was to minimize antibiotic use by following a standardized protocol in the pre-, peri- and postoperative setting, and adhere to American Urological Association antibiotic guidelines. We hypothesized that prolonged suppressive antibiotics post-urethroplasty does not prevent urinary tract infection and/or wound infection rates. MATERIALS AND METHODS: We prospectively treated 900 patients undergoing urethroplasty or perineal urethrostomy at 11 centers over 2 years. The first-year cohort A received prolonged postoperative antibiotics. Year 2, cohort B, did not receive prolonged antibiotics. A standardized protocol following the American Urological Association guidelines for perioperative antibiotics was used. The 30-day postoperative infectious complications were determined. We used chi-square analysis to compare the cohorts, and multivariate logistic regression to identify risk factors. RESULTS: The mean age of participants in both cohorts was 49.7 years old and the average stricture length was 4.09 cm. Overall, the rate of postoperative urinary tract infection and wound infection within 30 days was 5.1% (6.7% in phase 1 vs 3.9% in phase 2, p=0.064) and 3.9% (4.1% in phase 1 vs 3.7% in phase 2, p=0.772), respectively. Multivariate logistic regression analysis of patient characteristics and operative factors did not reveal any factors predictive of postoperative infections. CONCLUSIONS: The use of a standardized protocol minimized antibiotic use and demonstrated no benefit to prolonged antibiotic use. There were no identifiable risk factors when considering surgical characteristics. Given the concern of antibiotic over-prescription, we do not recommend prolonged antibiotic use after urethral reconstruction.

Defining Success after Anterior Urethroplasty: An Argument for a Universal Definition and Surveillance Protocol.

PURPOSE: A successful urethroplasty has been defined in different ways across studies. This variety in the literature makes it difficult to compare success rates and techniques across studies. We aim to evaluate the success of anterior urethroplasty based on different definitions of success in a single cohort. MATERIALS AND METHODS: Data were collected from a multi-institutional, prospectively maintained database. We included men undergoing first-time, single-stage, anterior urethroplasty between 2006 and 2020. Exclusion criteria included lack of followup, hypospadias, extended meatotomy, perineal urethrostomy, posterior urethroplasty and staged repairs. We compared 5 different ways to define a "failed" urethroplasty: 1) stricture retreatment, 2) anatomical recurrence on cystoscopy, 3) peak flow rate <15 ml/second, 4) weak stream on questionnaire and 5) failure by any of these measures. Kaplan-Meier survival curves were generated for each of the definitions. We also compared outcomes by stricture length, location and etiology. RESULTS: A total of 712 men met inclusion criteria, including completion of all types of followup. The 1- and 5-year estimated probabilities of success were "retreatment," 94% and 75%; "cystoscopy," 88% and 71%; "uroflow," 84% and 58%; "questionnaire," 67% and 37%; and "any failure," 57% and 23%. This pattern was inconsistent across stricture length, location and etiology. CONCLUSIONS: The estimated probability of success after first-time, anterior urethroplasty is highly dependent on the way success is defined. The variability in definitions in the literature has limited our ability to compare urethroplasty outcomes across studies.

Evidence for Proline Catabolic Enzymes in the Metabolism of Thiazolidine Carboxylates.

Thiazolidine carboxylates such as thiazolidine-4-carboxylate (T4C) and thiazolidine-2-carboxylate (T2C) are naturally occurring sulfur analogues of proline. These compounds have been observed to have both beneficial and toxic effects in cells. Given that proline dehydrogenase has been proposed to be a key enzyme in the oxidative metabolism of thioprolines, we characterized T4C and T2C as substrates of proline catabolic enzymes using proline utilization A (PutA), which is a bifunctional enzyme with proline dehydrogenase (PRODH) and l-glutamate-γ-semialdehyde dehydrogenase (GSALDH) activities. PutA is shown here to catalyze the FAD-dependent PRODH oxidation of both T4C and T2C with catalytic efficiencies significantly higher than with proline. Stopped-flow experiments also demonstrate that l-T4C and l-T2C reduce PutA-bound FAD at rates faster than proline. Unlike proline, however, oxidation of T4C and T2C does not generate a substrate for NAD+-dependent GSALDH. Instead, PutA/PRODH oxidation of T4C leads to cysteine formation, whereas oxidation of T2C generates an apparently stable Δ4-thiazoline-2-carboxylate species. Our results provide new insights into the metabolism of T2C and T4C.

Oh G: The x, y and z of human physiological responses to acceleration.

NEW FINDINGS: What is the topic of this review? This review focuses on the main physiological challenges associated with exposure to acceleration in the Gx, Gy and Gz directions and to microgravity. What advances does it highlight? Our current understanding of the physiology of these environments and latest strategies to protect against them are discussed in light of the limited knowledge we have in some of these areas. ABSTRACT: The desire to go higher, faster and further has taken us to environments where the accelerations placed on our bodies far exceed or are much lower than that attributable to Earth's gravity. While on the ground, racing drivers of the fastest cars are exposed to high degrees of lateral acceleration (Gy) during cornering. In the air, while within the confines of the lower reaches of Earth's atmosphere, fast jet pilots are routinely exposed to high levels of acceleration in the head-foot direction (Gz). During launch and re-entry of suborbital and orbital spacecraft, astronauts and spaceflight participants are exposed to high levels of chest-back acceleration (Gx), whereas once in space the effects of gravity are all but removed (termed microgravity, µG). Each of these environments has profound effects on the homeostatic mechanisms within the body and can have a serious impact, not only for those with underlying pathology but also for healthy individuals. This review provides an overview of the main challenges associated with these environments and our current understanding of the physiological and pathophysiological adaptations to them. Where relevant, protection strategies are discussed, with the implications of our future exposure to these environments also being considered.

Cautionary Tale of Using Tris(alkyl)phosphine Reducing Agents with NAD+-Dependent Enzymes.

Protein biochemistry protocols typically include disulfide bond reducing agents to guard against unwanted thiol oxidation and protein aggregation. Commonly used disulfide bond reducing agents include dithiothreitol, ß-mercaptoethanol, glutathione, and the tris(alkyl)phosphine compounds tris(2-carboxyethyl)phosphine (TCEP) and tris(3-hydroxypropyl)phosphine (THPP). While studying the catalytic activity of the NAD(P)H-dependent enzyme Δ1-pyrroline-5-carboxylate reductase, we unexpectedly observed a rapid non-enzymatic chemical reaction between NAD+ and the reducing agents TCEP and THPP. The product of the reaction exhibits a maximum ultraviolet absorbance peak at 334 nm and forms with an apparent association rate constant of 231-491 M-1 s-1. The reaction is reversible, and nuclear magnetic resonance characterization (1H, 13C, and 31P) of the product revealed a covalent adduct between the phosphorus of the tris(alkyl)phosphine reducing agent and the C4 atom of the nicotinamide ring of NAD+. We also report a 1.45 Å resolution crystal structure of short-chain dehydrogenase/reductase with the NADP+-TCEP reaction product bound in the cofactor binding site, which shows that the adduct can potentially inhibit enzymes. These findings serve to caution researchers when using TCEP or THPP in experimental protocols with NAD(P)+. Because NAD(P)+-dependent oxidoreductases are widespread in nature, our results may be broadly relevant.

Phosphorus NMR and Its Application to Metabolomics.

Stable isotopes are routinely employed by NMR metabolomics to highlight specific metabolic processes and to monitor pathway flux. 13C-carbon and 15N-nitrogen labeled nutrients are convenient sources of isotope tracers and are commonly added as supplements to a variety of biological systems ranging from cell cultures to animal models. Unlike 13C and 15N, 31P-phosphorus is a naturally abundant and NMR active isotope that does not require an external supplemental source. To date, 31P NMR has seen limited usage in metabolomics because of a lack of reference spectra, difficulties in sample preparation, and an absence of two-dimensional (2D) NMR experiments, but 31P NMR has the potential of expanding the coverage of the metabolome by detecting phosphorus-containing metabolites. Phosphorylated metabolites regulate key cellular processes, serve as a surrogate for intracellular pH conditions, and provide a measure of a cell's metabolic energy and redox state, among other processes. Thus, incorporating 31P NMR into a metabolomics investigation will enable the detection of these key cellular processes. To facilitate the application of 31P NMR in metabolomics, we present a unified protocol that allows for the simultaneous and efficient detection of 1H-, 13C-, 15N-, and 31P-labeled metabolites. The protocol includes the application of a 2D 1H-31P HSQC-TOCSY experiment to detect 31P-labeled metabolites from heterogeneous biological mixtures, methods for sample preparation to detect 1H-, 13C-, 15N-, and 31P-labeled metabolites from a single NMR sample, and a data set of one-dimensional (1D) 31P NMR and 2D 1H-31P HSQC-TOCSY spectra of 38 common phosphorus-containing metabolites to assist in metabolite assignments.

Outcomes and Risk Factors of Revision and Replacement Artificial Urinary Sphincter Implantation in Radiated and Nonradiated Cases.

PURPOSE: Risk factors for complications after artificial urinary sphincter surgery include a history of pelvic radiation and prior artificial urinary sphincter complication. The survival of a second artificial urinary sphincter in the setting of prior device complication and radiation is not well described. We report the survival of redo artificial urinary sphincter surgery and identify risk factors for repeat complications. MATERIALS AND METHODS: A multi-institutional database was queried for redo artificial urinary sphincter surgeries. The primary outcome was median survival of a second and third artificial urinary sphincter in radiated and nonradiated cases. A Cox proportional hazards survival analysis was performed to identify additional patient and surgery risk factors. RESULTS: Median time to explantation of the initial artificial urinary sphincter in radiated (150) and nonradiated (174) cases was 26.4 and 35.6 months, respectively (p=0.043). For a second device median time to explantation was 30.1 and 38.7 months (p=0.034) and for a third device it was 28.5 and 30.6 months (p=0.020), respectively. The 5-year revision-free survival for patients undergoing a second artificial urinary sphincter surgery with no risk factors, history of radiation, history of urethroplasty, and history of radiation and urethroplasty were 83.1%, 72.6%, 63.9% and 46%, respectively. CONCLUSIONS: Patients without additional risk factors undergoing second and third artificial urinary sphincter surgeries experience revision-free rates similar to those of their initial artificial urinary sphincter devices. Patients who have been treated with pelvic radiation have earlier artificial urinary sphincter complications. When multiple risk factors exist, revision-free rates decrease significantly.

Multicenter analysis of posterior urethroplasty complexity and outcomes following pelvic fracture urethral injury.

PURPOSE: To analyze outcomes of posterior urethroplasty following pelvic fracture urethral injuries (PFUI) and to determine risk factors for surgical complexity and success. METHODS: Patients who underwent posterior urethroplasty following PFUI were identified in the Trauma and Urologic Reconstructive Network of Surgeons (TURNS) database. Demographics, injury patterns, management strategies, and prior interventions were evaluated. Risk factors for surgical failure and the impact of ancillary urethral lengthening maneuvers (corporal splitting, pubectomy and supracrural rerouting) were evaluated. RESULTS: Of the 436 posterior urethroplasties identified, 122 were following PFUI. 83 (68%) patients were acutely managed with suprapubic tubes, while 39 (32%) underwent early endoscopic realignment. 16 (13%) patients underwent pelvic artery embolization in the acute setting. 116 cases (95%) were completed via a perineal approach, while 6 (5%) were performed via an abdominoperineal approach. The need for one or more ancillary maneuvers to gain urethral length occurred in 4 (36%) patients. Of these, 44 (36%) received corporal splitting, 16 (13%) partial or complete pubectomy, and 2 (2%) supracrural rerouting. Younger patients, those with longer distraction defects, and those with a history of angioembolization were more likely to require ancillary maneuvers. 111 patients (91%) did not require repeat intervention during follow-up. Angioembolization (p = 0.03) and longer distraction defects (p = 0.01) were associated with failure. CONCLUSIONS: Posterior urethroplasty provides excellent success rates for patients following PFUI. Pelvic angioembolization and increased defect length are associated with increased surgical complexity and risk of failure. Surgeons should be prepared to implement ancillary maneuvers when indicated to achieve a tension-free anastomosis.

Clinical significance of cystoscopic urethral stricture recurrence after anterior urethroplasty: a multi-institution analysis from Trauma and Urologic Reconstructive Network of Surgeons (TURNS).

PURPOSE: To assess the functional Queryoutcome of patients with cystoscopic recurrence of stricture post-urethroplasty and to evaluate the role of cystoscopy as initial screening tool to predict future failure. METHODS: Cases with cystoscopy data after anterior urethroplasty in a multi-institutional database were retrospectively studied. Based on cystoscopic evaluation, performed within 3-months post-urethroplasty, patients were categorized as small-caliber (SC) stricture recurrence: stricture unable to be passed by standard cystoscope, large-caliber (LC) stricture accommodating a cystoscope, and no recurrence. We assessed the cumulative probability of intervention and the quality of life scores in association with cystoscopic recurrence 1-year post-urethroplasty. Patients with history of hypospadias, perineal urethrostomy, urethral fistula, and meatal pathology were excluded. RESULTS: From a total of 2630 men in our cohort, 1054 patients met the inclusion criteria: normal (n = 740), LC recurrence (n = 178), and SC recurrence (n = 136) based on the first cystoscopic evaluation performed at median 111 days postoperatively. Median follow-up was 350 days (IQR 121-617) after urethroplasty. Cystoscopic recurrence was significantly associated with secondary interventions (2.7%, 6.2%, 33.8% in normal, LC, and SC groups, respectively). Quality of life variables were not statistically significantly different among the three study groups. CONCLUSIONS: Many patients with cystoscopic recurrence do not need an intervention after initial urethroplasty. Despite good negative predictive value, cystoscopy alone may be a poor screening test for stricture recurrence defined by patient symptoms and need for secondary interventions.

Multicenter Analysis of Patient Reported Outcomes Following Artificial Urinary Sphincter Placement for Male Stress Urinary Incontinence.

PURPOSE: Patient centered data are lacking regarding functional and quality of life improvements after artificial urinary sphincter placement. We analyzed the degree of benefit from artificial urinary sphincter placement using ISI (Incontinence Symptom Index), a validated patient reported outcome measure assessing the severity and bother of urinary incontinence, and IIQ-7 (Incontinence Impact Questionnaire-7), a validated patient reported outcome measure assessing the impact and emotional distress of urinary incontinence. MATERIALS AND METHODS: We performed a retrospective review at 4 centers participating in TURNS (Trauma and Urologic Reconstruction Network of Surgeons). Data were available on 51 and 45 patients who underwent artificial urinary sphincter placement, and had preoperative and postoperative ISI and IIQ-7 data, respectively. RESULTS: Mean age was 64.8 years. Median time from surgery to followup questionnaires was 8.5 months. On ISI the median preoperative severity and bother scores were 24 (IQR 20-28.5) and 6 (IQR 4-7), and the median postoperative severity and bother scores were 10 (IQR 4.5-17) and 1 (IQR 0-3), respectively. Improvement on each ISI item was statistically significant. On IIQ-7 the median preoperative impact and distress scores were 9 (IQR 6-13) and 4 (IQR 2-6), and the median postoperative impact and distress scores were 3 (IQR 0-7) and 0 (IQR 0-3), respectively. Improvement on each IIQ-7 item was statistically significant. CONCLUSIONS: Artificial urinary sphincter implantation significantly reduces the severity and bother of stress urinary incontinence symptoms. Longer followup and development are needed of a patient reported outcome measure targeting male stress urinary incontinence.

Multi-Institutional Outcomes of Endoscopic Management of Stricture Recurrence after Bulbar Urethroplasty.

PURPOSE: Approximately 10% to 20% of patients will have a recurrence after urethroplasty. Initial management of these recurrences is often by urethral dilation or direct vision internal urethrotomy. In the current study we describe the outcomes of endoscopic management of stricture recurrence after bulbar urethroplasty. MATERIALS AND METHODS: We retrospectively reviewed bulbar urethroplasty data from 5 surgeons in the TURNS (Trauma and Urologic Reconstruction Network of Surgeons). Men who underwent urethral dilation or direct vision internal urethrotomy for urethroplasty recurrence were identified. Recurrence was defined as the inability to pass a 17Fr cystoscope through the area of reconstruction. The primary outcome was the success rate of recurrence management. Comparisons were made between urethral dilation and direct vision internal urethrotomy, and then between endoscopic management of recurrences after excision and primary anastomosis urethroplasty vs substitutional repairs using time to event statistics. RESULTS: In 53 men recurrence was initially managed endoscopically. Median time to urethral stricture recurrence after urethroplasty was 5 months. At a median followup of 5 months the overall success rate was 42%. Success after urethral dilation was significantly less than after direct vision internal urethrotomy (1 of 10 patients or 10% vs 21 of 43 or 49%, p <0.001) with a failure HR of 3.15 (p = 0.03). Direct vision internal urethrotomy was more effective after substitutional failure than after excision and primary anastomosis urethroplasty (53% vs 13%, p = 0.005). CONCLUSIONS: Direct vision internal urethrotomy was more successful than urethral dilation in the management of stricture recurrence after bulbar urethroplasty. Direct vision internal urethrotomy was more successful in patients with recurrence after substitution urethroplasty compared to after excision and primary anastomosis urethroplasty. Perhaps this indicates a different mechanism of recurrence for excision and primary anastomosis urethroplasty (ischemic) vs substitution urethroplasty (nonischemic).

Prevalence of Post-Micturition Incontinence before and after Anterior Urethroplasty.

PURPOSE: In this study we aimed to define the prevalence of preoperative and postoperative post-micturition incontinence or post-void dribbling after anterior urethroplasty for urethral stricture disease. We also sought to determine risk factors for its presence. MATERIALS AND METHODS: We retrospectively reviewed a prospectively maintained, multi-institutional urethral stricture database to evaluate post-micturition incontinence using a single question from a validated questionnaire, "How often have you had a slight wetting of your pants a few minutes after you had finished urinating and had dressed yourself?" Possible answers were never-0 to all the time-3. The presence of post-micturition incontinence was defined as any answer greater than 0. Comparisons were made to stricture type and location, repair type and patient medical comorbidities. RESULTS: Preoperative and postoperative post-micturition incontinence questionnaires were completed by 614 and 331 patients, respectively. Patients without complete data available were excluded from study. Preoperative post-micturition incontinence was present in 73% of patients, of whom 44% stated that this symptom was present most of the time. Overall postoperative post-micturition incontinence was present in 40% of patients and again it was not predicted by stricture location or urethroplasty type. Of the 331 patients with followup questionnaires 60% reported improvement, 32% reported no change and 8% reported worsening symptoms. The overall rate of de novo post-micturition incontinence was low at 6.3%. CONCLUSIONS: The prevalence of preoperative post-micturition incontinence is high and likely under reported. In most patients post-micturition incontinence improves after urethroplasty and the prevalence of de novo post-micturition incontinence is low. The presence of post-micturition incontinence was not predicted by stricture length or location, or urethroplasty repair type.

Determinants of ventilation and pulmonary artery pressure during early acclimatization to hypoxia in humans.

Pulmonary ventilation and pulmonary arterial pressure both rise progressively during the first few hours of human acclimatization to hypoxia. These responses are highly variable between individuals, but the origin of this variability is unknown. Here, we sought to determine whether the variabilities between different measures of response to sustained hypoxia were related, which would suggest a common source of variability. Eighty volunteers individually underwent an 8-h isocapnic exposure to hypoxia (end-tidal P(O2)=55 Torr) in a purpose-built chamber. Measurements of ventilation and pulmonary artery systolic pressure (PASP) assessed by Doppler echocardiography were made during the exposure. Before and after the exposure, measurements were made of the ventilatory sensitivities to acute isocapnic hypoxia (G(pO2)) and hyperoxic hypercapnia, the latter divided into peripheral (G(pCO2)) and central (G(cCO2)) components. Substantial acclimatization was observed in both ventilation and PASP, the latter being 40% greater in women than men. No correlation was found between the magnitudes of pulmonary ventilatory and pulmonary vascular responses. For G(pO2), G(pCO2) and G(cC O2), but not the sensitivity of PASP to acute hypoxia, the magnitude of the increase during acclimatization was proportional to the pre-acclimatization value. Additionally, the change in G(pO2) during acclimatization to hypoxia correlated well with most other measures of ventilatory acclimatization. Of the initial measurements prior to sustained hypoxia, only G(pCO2) predicted the subsequent rise in ventilation and change in G(pO2) during acclimatization. We conclude that the magnitudes of the ventilatory and pulmonary vascular responses to sustained hypoxia are predominantly determined by different factors and that the initial G(pCO2) is a modest predictor of ventilatory acclimatization.

Understanding the Relationship between Chronic Systemic Disease and Lichen Sclerosus Urethral Strictures.

PURPOSE: Lichen sclerosus is a chronic, inflammatory skin condition of the genitalia of unknown origin that accounts for nearly 10% of urethral stricture disease. In this study we determine systemic comorbidities associated with lichen sclerosus in men. MATERIALS AND METHODS: We analyzed data from 1,151 men who were enrolled in a multi-institutional prospective urethroplasty outcomes database. Individuals were grouped by stricture etiology, and baseline demographics, medical histories and patient reported outcome measures were retrospectively compared across groups. RESULTS: Of the 1,151 men in the database 81 (7.0%) were noted to have lichen sclerosus related urethral stricture disease. Average patient age was 46.06 ± 16.52 years, with those with lichen sclerosus being significantly older than those without lichen sclerosus (51.26 ± 13.84 vs 45.68 ± 16.64, p = 0.0011). Men with lichen sclerosus were more likely to have hypertension, hyperlipidemia and diabetes, and to use tobacco products. Controlling for age, men with lichen sclerosus related urethral stricture disease had a higher body mass index (aOR 1.089, 95% CI 1.050-1.130), and were more likely to have hypertension (aOR 2.028, 1.21-3.41) and be active tobacco users (aOR 2.0, 1.36-3.40). Mean preoperative patient reported outcome measures scores for urinary and sexual function were similar. Controlling for stricture length and location, the adjusted odds of surgical failure were higher for lichen sclerosus related urethral stricture disease (aOR 1.9, 95% CI 0.9-4.2). CONCLUSIONS: Lichen sclerosus related urethral stricture disease is associated with chronic systemic diseases. This association may implicate a systemic inflammatory and/or autoimmune pathophysiology. A 2-hit mechanism implicating local and systemic factors for lichen sclerosus related urethral stricture disease development and progression is hypothesized.