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ObjectivesTo identify predictors of early artificial sphincter (AUS) erosion among a cohort of men with erosion, who underwent AUS placement by either university or community-based surgeons.MethodsThe records of all patients with AUS erosions, including men who underwent AUS placement at outside facilities, were retrospectively reviewed. A Cox proportional-hazards model for time to erosion was performed with the predictors being the components of a fragile urethra (history of radiation, prior AUS, prior urethroplasty), androgen deprivation therapy (ADT), trans-corporal (TC), and 3.5 cm cuff, controlling for other risk factors. Kaplan-Meier survival curves and log-rank test compared "fragile" urethras with "not fragile" urethras. All statistical analysis was done using R version 3.5.2.ResultsOf the 156 men included, 36% had undergone AUS placement in the community. Median time to erosion was 16.0 months (1.0-240.0 months), and 122 (78%) met at least one fragility criteria. Radiation (HR 2.36, 95% CI 1.52-3.64) and prior urethroplasty (HR 2.12, 95% CI 1.18-3.80) were independently associated with earlier time to erosion. The Kaplan-Meier estimates demonstrate 1- and 5-year survival rates of 76.5% and 50.0%, respectively, for "non-fragile" and 44.1% and 14.8% for "fragile" urethras (P < .0001).ConclusionIn a diverse cohort of men with AUS erosion, men with "fragile" urethras eroded sooner. Radiation and prior urethroplasty were independent risk factors for earlier time to erosion, but prior AUS, ADT, TC and 3.5 cm cuff were not.

Objective To determine surgical site infection and urinary tract infection (UTI) rates in the setting of urethroplasty. Given significant variation in the utilization of antibiotics, there is an opportunity to improve antibiotic stewardship. This study aims to elucidate the rate of both UTI and surgical site infection after urethroplasty on a standardized perioperative antibiotic regimen, and to obtain patient and operative characteristics that may predict infection. Methods We prospectively treated 390 patients undergoing urethroplasty at 11 centers with a standardized perioperative antibiotic protocol. Patients had a urine culture or urine analysis within 3 weeks of surgery. After surgery, patients were discharged with an indwelling catheter, removed per usual surgeon practice. All were given nitrofurantoin from discharge until catheter removal. Logistic regression analyses were performed to determine the correlation between patient characteristics or operative categories with post-operative infection. Results The rates of postoperative UTI and wound infection within 30 days were 6.7% and 4.1%, respectively. On multivariate analysis of demographics, comorbidities, and stricture characteristics and repair, only preoperative UTI (P = .012), history of cardiovascular disease (P = .015), and performing a membranous urethroplasty (0.018) were significant predictors of a UTI within 30 days postoperatively. Location of repair nor graft use increased the risk of UTI. There were no factors predictive of postoperative wound infection. Conclusion A standardized antibiotic protocol was created to narrow and limit excess antibiotic use. This protocol, with clear definitions of UTI and wound infection, allowed determination of accurate infection rates in urethroplasties. Preoperative UTI, even when properly treated, increases the risk of postoperative UTI.

PurposeThere 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 methodsWe 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.ResultsThe 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.ConclusionsThe 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.

PurposeA 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 methodsData 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

Rapid response to the current coronavirus disease 2019 (COVID-19) pandemic requires fast dissemination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequence data in order to align diagnostic tests and vaccines with the natural evolution of the virus as it spreads through the world. To facilitate this, the National Library of Medicine’s National Center for Biotechnology Information developed an automated pipeline for the deposition and quick processing of SARS-CoV-2 genome assemblies into GenBank for the user community. The pipeline ensures the collection of contextual information about the virus source, assesses sequence quality and annotates descriptive biological features, such as protein-coding regions and mature peptides. The process promotes standardized nomenclature and creates and publishes fully processed GenBank files within minutes of deposition. The software has processed and published 982 454 annotated SARS-CoV-2 sequences, as of 21 October 2021. This development addresses the needs of the scientific community as the sequencing of SARS-CoV-2 genomes increases and will facilitate unrestricted access to and usability of SARS-CoV-2 genomic sequence data, providing important reagents for scientific and public health activities in response to the COVID-19 pandemic. Database URL https://submit.ncbi.nlm.nih.gov/sarscov2/genbank/

BACKGROUND: Members of the public will soon be taking commercial suborbital spaceflights with significant Gx (chest-to-back) acceleration potentially reaching up to 6 Gx. Pulmonary physiology is gravity-dependent and is likely to be affected, which may have clinical implications for medically susceptible individuals.METHODS: During 2-min centrifuge exposures ranging up to 6 Gx, 11 healthy subjects were studied using advanced respiratory techniques. These sustained exposures were intended to allow characterization of the underlying pulmonary response and did not replicate actual suborbital G profiles. Regional distribution of ventilation in the lungs was determined using electrical impedance tomography. Neural respiratory drive (from diaphragm electromyography) and work of breathing (from transdiaphragmatic pressures) were obtained via nasoesophageal catheters. Arterial blood gases were measured in a subset of subjects. Measurements were conducted while breathing air and breathing 15 oxygen to simulate anticipated cabin pressurization conditions.RESULTS: Acceleration caused hypoxemia that worsened with increasing magnitude and duration of Gx. Minimum arterial oxygen saturation at 6 Gx was 86 1 breathing air and 79 1 breathing 15 oxygen. With increasing Gx the alveolar-arterial (A-a) oxygen gradient widened progressively and the relative distribution of ventilation reversed from posterior to anterior lung regions with substantial gas-trapping anteriorly. Severe breathlessness accompanied large progressive increases in work of breathing and neural respiratory drive.DISCUSSION: Sustained high-G acceleration at magnitudes relevant to suborbital flight profoundly affects respiratory physiology. These effects may become clinically important in the most medically susceptible passengers, in whom the potential role of centrifuge-based preflight evaluation requires further investigation.Pollock RD, Jolley CJ, Abid N, Couper JH, Estrada-Petrocelli L, Hodkinson PD, Leonhardt S, Mago-Elliott S, Menden T, Rafferty G, Richmond G, Robbins PA, Ritchie GAD, Segal MJ, Stevenson AT, Tank HD, Smith TG. Pulmonary effects of sustained periods of high-G acceleration relevant to suborbital spaceflight. Aerosp Med Hum Perform. 2021; 92(7):633641.

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.

Objective To analyze contemporary urethroplasty trends and urethral stricture etiologies over a 7-year study period among urologists from a large multi-institutional surgical outcomes group. Methods Review of a multi-institutional, prospectively maintained urethroplasty database was performed on 2098 anterior urethroplasties done between 2010 and 2017 by 10 surgeons. Stricture characteristics, including etiology, length, and anatomic location were analyzed and compared to urethroplasty type over the study period using chi-squared analysis to assess for linear trends within the group and by surgeon. Results Average stricture lengths for bulbar (2.8 ± 1.8 cm), penile (3.6 ± 2.6 cm), and penile-bulbar strictures (8.7 ± 5.0) remained stable. The most common stricture etiology was idiopathic/unknown in all study years (63%). In the bulbar urethra, the group performed significantly (1) fewer excisional repairs (−31%) and more substitutional repairs (+78%); (2) of substitutional repairs, more grafts are being placed dorsally (+95%) vs ventrally (−75%) (3) of the bulbar excisional repairs, more are being performed without transection of the bulbar urethra (+430%); and in the penile urethra (4) the fasciocutaneous flap is in decline (−86%), while single-stage dorsal repairs are increasing (+280%). Conclusion Anterior urethroplasty techniques continue to evolve in the absence of robust clinical data or randomized controlled trials, with a general movement in this cohort toward an initial dorsal approach for most strictures. Inter- and intrasurgeon variability in the surgical management of similar strictures was noted, and the feasibility of any future randomized controlled trials, without apparent surgical equipoise, must be questioned.

Objective : To evaluate risks of peri-operative ureteral catheter placement in a consecutive patient-series. Methods : Patients who underwent peri-operative ureteral catheter placement at a single institution in 2018 were included. A retrospective review was conducted to evaluate patient and procedure related characteristics, including data on technique, perceived placement difficulty, operative details, and complications. Outcome Measurements and Statistical Analysis : Urologic complications within 30 days were evaluated using the Clavien-Dindo system. Statistical analysis for association was conducted using the X2 test or fisher's exact tests. Results : 413 patients were included. 50/413 (12.1%) cases had urologic complications within 30 days. 43 were Clavien-Dindo grade I-II. Six were grade III. 5/6 patients had oliguric, obstructive AKI. One had flank pain with hydronephrosis. Two patients each underwent placement of unilateral nephrostomy tube, bilateral double-J stent placement, and unilateral stent placement. One patient had a Grade V complication. They developed multi-system organ failure including renal failure with hydronephrosis.All patients who required re-intervention had bilateral peri-operative catheterization with use of a wire. Intraoperative difficulty with placement was associated with high-grade complication (p Conclusions : Rate of acute complication following ureteral catheter placement is 12%. 1.7% of patients develop post-operative ureteral obstruction requiring intervention within 30 days. Future studies are needed to determine patients most at risk for post-ureteral stent complication.

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.

Background To determine if the number of endoscopic treatments of urethral stricture disease (USD) prior to urethroplasty has changed in the context of new AUA guidelines on management of USD. In addition to an increase in practicing reconstructive urologists and published reconstructive literature, the AUA guidelines regarding the management of male USD were presented in May 2016, advocating consideration of urethroplasty in patients with 1 prior failed endoscopic treatment. Methods A retrospective review of a prospectively maintained, multi-institutional urethral stricture database of high volume, geographically diverse institutions was performed from 2006 to 2017. We performed a review of relevant literature and evaluated pre-urethroplasty endoscopic treatment patterns prior to and after the AUA male stricture guideline. Results 2964 urethroplasties were reviewed in 10 institutions. There was both a decrease in the number of endoscopic treatments prior to urethroplasty in the pre-May 2016 compared to post-May 2016 cohorts both for overall urethroplasties (2.3 vs 1.6, P = 0.0012) and a gradual decrease in the number of pre-urethroplasty endoscopic treatments over the entire study period. Conclusion There was a decrease in the number of endoscopic treatments of USD prior to urethroplasty in the observed period of interest. Declining endoscopic USD management is not likely to be a reflection of a solely unique influence of the guidelines as endoscopic treatment decreased over the entire study period. Further research is needed to determine if there will be a continued trend in the declining use of endoscopic treatment and elucidate the barriers to earlier urethroplasty in patients with USD.

Objective To develop and validate a clinical classification system for urethral stricture disease (USD) based on the retrograde urethrogram (RUG), physical exam, and stricture-specific patient history. Materials and methods Three elements were chosen to be included in the classification system: 1) Length of urethral stricture (L); 2) Stricture segment/location (S); 3) Stricture Etiology (E) (LSE classification system). Each element was divided into clinically relevant sub-categories. A three-step development and validation process then ensued, culminating in an in-person Trauma and Urologic Reconstruction Network of Surgeons (TURNS) meeting, at which the final classification system was unanimously agreed upon by attendees based on interrater reliability data obtained from the classifying of 22 clinical vignettes. A final validation step involved retrospectively classifying cases in the TURNS database to determine if classification influenced surgical technique and was associated with presumed stricture etiology. Results The final LSE classification system was found to have an interrater reliability of 0.79 (individual components 0.76, 0.70 and 0.93 respectfully). Retrospective classification of the 2162 TURNS strictures revealed the segment (S) to be strongly associated with urethroplasty type (p = 0.0005) and stricture etiology (E) (p = 0.0005). Conclusion We developed and validated a novel, easy to use, urethral stricture classification system. The system's ability to aid in directing treatments, predict treatment outcomes, and facilitate collaborative research efforts will require further study.

Objective. During launch and atmospheric re-entry in suborbital space flights, astronauts are exposed to high G-acceleration. These acceleration levels influence gas exchange inside the lung and can potentially lead to hypoxaemia. The distribution of air inside the lung can be monitored by Electrical Impedance Tomography (EIT). This imaging technique might reveal how high gravitational forces affect the dynamic behavior of ventilation and impair gas exchange resulting in hypoxaemia. Approach. We performed a trial in a long-arm centrifuge with ten participants lying supine while being exposed to +2, +4 and +6\,Gx (chest-to-back acceleration) to study the magnitude of accelerations experienced during suborbital spaceflight. Main results. First, the tomographic images revealed that the dorsal region of the lung emptied faster than the ventral region. Second, the ventilated area shifted from dorsal to ventral. Consequently, alveolar pressure in the dorsal area reached the pressure of the upper airways before the ventral area emptied completely. Finally, the upper airways collapsed and the end-expiratory volume increased. This resulted in ventral gas trapping with restricted gas exchange. Significance. At +4x changes in ventilation distribution varied considerably between subjects potentially due to variation in individual physical conditions. However, at +6\,Gx all participants were affected similarly and the influence of high gravitational conditions was pronounced.

Objective To evaluate the success of urethroplasty for urethral strictures arising after erosion of an artificial urinary sphincter (AUS) and rates of subsequent AUS replacement. Patients and Methods From 2009-2016, we identified patients from the Trauma and Urologic Reconstruction Network of Surgeons and several other centers. We included patients with urethral strictures arising from AUS erosion undergoing urethroplasty with or without subsequent AUS replacement. We retrospectively reviewed patient demographics, history, stricture characteristics, and outcomes. Variables in patients with and without complications after AUS replacement were compared using chi-square test, independent samples t test, and Mann-Whitney U test when appropriate. Results Thirty-one men were identified with the inclusion criteria. Radical prostatectomy was the etiology of incontinence in 87% of the patients, and 29% had radiation therapy. Anastomotic (28) and buccal graft substitution (3) urethroplasty were performed. Follow-up cystoscopy was done in 28 patients (median 4.5 months, interquartile range [IQR]: 3-8) showing no urethral stricture recurrences. Median overall follow-up was 22.0 months (IQR: 15-38). In 27 men (87%), AUS was replaced at median of 6.0 months (IQR: 4-7) after urethroplasty. In 25 patients with >3 months of follow-up after AUS replacement, urethral complications requiring AUS revision or removal occurred in 9 patients (36%) and included subcuff atrophy (3) and erosion (6). Mean length of stricture was higher in patients who developed a complication after urethroplasty and AUS replacement (2.2 vs. 1.5 cm, P = .04). Conclusion In patients with urethral stricture after AUS erosion, urethroplasty is successful. However, AUS replacement after urethroplasty has a high erosion rate even in the short-term.

To analyze outcomes of posterior urethroplasty following pelvic fracture urethral injuries (PFUI) and to determine risk factors for surgical complexity and success. 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. 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. 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.

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.

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

Given the poor understanding of the pathophysiology of genital lichen sclerosus (GLS) and a lack of accepted definitive diagnostic criteria, we proposed to survey pathologists regarding their understanding of GLS. We hypothesized that significant disagreement about GLS will exist.All urologists participating in the Trauma and Urologic Reconstruction Network of Surgeons identified genitourinary (GUP) and dermatopathologists (DP) at their respective institutions who were then invited to participate in an online survey regarding their experience with diagnosing GLS, GLS pathophysiology and its relationship to urethral stricture disease.There were 23 (12 DP, 11 GUP) pathologists that completed the survey. The most agreed upon criteria for diagnosis were dermal collagen homogenization (85.7%), loss of the normal rete pattern (33.3%) and atrophic epidermis (28.5%). No pathologists believed GLS had an infectious etiology (19% maybe, 42% unknown) and 19% believed GLS to be an autoimmune disorder (42% maybe, 38% unknown); 19% believed LS to be premalignant, but 52% believed it was associated with cancer; 80% believed that LS could involve the urethra (DP (92%) versus GUP (67%); p = 0.272). Of those diagnosing urethral GLS, 80% of DUP believed that GLS must first involve the glans/prepuce before involving the urethra, while all GUP believed that urethral disease could exist in isolation (p = 0.007).There was significant disagreement in this specialized cohort of pathologists when diagnosing GLS. A logical first step appears to be improving agreement on how to best describe and classify the disease. This may lead to improve treatments.

PurposeIn 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 methodsWe 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.ResultsPreoperative 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%.ConclusionsThe 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.

PurposePatient 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 methodsWe 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.ResultsMean 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.ConclusionsArtificial 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.

Hypoxia-induced elevation in pulmonary artery pressure during air travel may contribute to the worldwide burden of in-flight medical emergencies. The pulmonary artery pressure response may be greater in older passengers, who are more likely to require flight diversion due to a medical event. Understanding these effects may ultimately improve the safety of air travel.We studied 16 healthy volunteers, consisting of a younger group (aged25 yr) and an older group (aged60 yr). Using a hypobaric chamber, subjects undertook a 2-h simulated flight at the maximum cabin pressure altitude for commercial airline flights (8000 ft; 2438 m). Higher and lower altitudes within the aeromedical range were also explored. Systolic pulmonary artery pressure (sPAP) was assessed by Doppler echocardiography.There was a progressive increase in sPAP which appeared to be biphasic, with a small initial increase and a larger subsequent rise. Overall, sPAP increased by 5±1 mmHg from baseline to 35±1 mmHg at 8000 ft, an increase of 18%. The sPAP response to 8000 ft was greater in the older group than the younger group.This study confirms that pulmonary artery pressure increases during simulated air travel, and provides preliminary evidence that this response is greater in older people. Advancing age may increase in-flight susceptibility to adverse pulmonary vascular responses in passengers, aircrew, and aeromedical patients.

Oxygen‐dependent regulation of the erythropoietin gene is mediated by the hypoxia‐inducible factor (HIF) family of transcription factors. When oxygen is plentiful, HIF undergoes hydroxylation by a family of oxygen‐dependent prolyl hydroxylase domain (PHD) proteins, promoting its association with the von Hippel‐Lindau (VHL) ubiquitin E3 ligase and subsequent proteosomal degradation. When oxygen is scarce, the PHD enzymes are inactivated, leading to HIF accumulation and upregulation not only of erythropoietin expression, but also the expression of hundreds of other genes, including those coordinating cardiovascular and ventilatory adaptation to hypoxia. Nevertheless, despite the identification of over 50 mutations in the PHD‐HIF‐VHL pathway in patients with previously unexplained congenital erythrocytosis, there are very few reports of associated cardiopulmonary abnormalities. We now report exaggerated pulmonary vascular and ventilatory responses to acute hypoxia in a 35‐year‐old man with erythrocytosis secondary to heterozygous mutation in PHD2, the most abundant of the PHD isoforms. We compare this phenotype with that reported in patients with the archetypal disorder of cellular oxygen sensing, Chuvash polycythemia, and discuss the possible clinical implications of our findings, particularly in the light of the emerging role for small molecule PHD inhibitors in clinical practice.

PurposeLittle published data exist on the impact of urethral stricture surgery on urinary urgency. We evaluated urinary urgency and urge incontinence before and after anterior urethroplasty.Materials and methodsMale patients who underwent 1-stage anterior urethroplasty were retrospectively identified at 8 centers. Patients with preoperative and 2-month or greater postoperative subjective urinary urgency assessments were included in study. Patients who received anticholinergic medications preoperatively were excluded. Univariate and multivariate analysis was done to analyze the association of patient characteristics with preoperative and postoperative symptoms as well as improvement or worsening of symptoms after surgery.ResultsSymptom and followup data on urgency and urge incontinence were available in in 439 and 305 patients, respectively. Preoperatively 58% of the men reported urgency and 31% reported urge incontinence. Postoperatively this decreased to 40% of men for urgency and 12% for urge incontinence (each p

Background The von Hippel–Lindau tumour suppressor protein–hypoxia-inducible factor (VHL–HIF) pathway has attracted widespread medical interest as a transcriptional system controlling cellular responses to hypoxia, yet insights into its role in systemic human physiology remain limited. Chuvash polycythaemia has recently been defined as a new form of VHL-associated disease, distinct from the classical VHL-associated inherited cancer syndrome, in which germline homozygosity for a hypomorphic VHL allele causes a generalised abnormality in VHL–HIF signalling. Affected individuals thus provide a unique opportunity to explore the integrative physiology of this signalling pathway. This study investigated patients with Chuvash polycythaemia in order to analyse the role of the VHL–HIF pathway in systemic human cardiopulmonary physiology. Methods and Findings Twelve participants, three with Chuvash polycythaemia and nine controls, were studied at baseline and during hypoxia. Participants breathed through a mouthpiece, and pulmonary ventilation was measured while pulmonary vascular tone was assessed echocardiographically. Individuals with Chuvash polycythaemia were found to have striking abnormalities in respiratory and pulmonary vascular regulation. Basal ventilation and pulmonary vascular tone were elevated, and ventilatory, pulmonary vasoconstrictive, and heart rate responses to acute hypoxia were greatly increased. Conclusions The features observed in this small group of patients with Chuvash polycythaemia are highly characteristic of those associated with acclimatisation to the hypoxia of high altitude. More generally, the phenotype associated with Chuvash polycythaemia demonstrates that VHL plays a major role in the underlying calibration and homeostasis of the respiratory and cardiovascular systems, most likely through its central role in the regulation of HIF., Editors' Summary Background. Human cells (like those of other multicellular animals) use oxygen to provide the energy needed for daily life. Having not enough oxygen is a problem, but having too much is also dangerous because it damages proteins, DNA, and other large molecules that keep cells functioning. Consequently, the physiological systems—including the heart, lungs, and circulation—work together to balance oxygen supply and demand throughout the body. When oxygen is limiting (a condition called hypoxia), as happens at high altitudes, the cellular oxygen supply is maintained by increasing the heart rate, increasing the speed and depth of breathing (hyperventilation), constricting the blood vessels in the lung (pulmonary vasoconstriction), and increasing the number of oxygen-carrying cells in the blood. All these physiological changes increase the amount of oxygen that can be absorbed from the air, but how they are regulated is poorly understood. By contrast, researchers know quite a bit about how individual cells respond to hypoxia. When oxygen is limited, a protein called hypoxia-inducible factor (or HIF) activates a number of target proteins that help the cell get enough oxygen (for example, proteins that stimulate the growth of new blood vessels). When there is plenty of oxygen, another protein, called von Hippel–Lindau tumor suppressor (abbreviated VHL), rapidly destroys HIF. Recently, researchers discovered that a genetic condition called Chuvash polycythaemia, characterised by the overproduction of red blood cells, is caused by a specific defect in VHL that reduces its ability to destroy HIF. As a result, the expression of certain HIF target proteins is increased even when oxygen levels are normal. Why Was This Study Done? Chuvash polycythaemia is very rare, and so far little is known about how this genetic abnormality affects the physiology and long-term health of patients. By studying heart and lung function in patients with Chuvash polycythaemia, the researchers involved in this study hoped to discover more about the health consequences of the condition and to find out whether the VHL–HIF system controls systemic responses to hypoxia as well as cellular responses. What Did the Researchers Do and Find? The researchers recruited and studied three patients with Chuvash polycythaemia, and, as controls for the comparison, several normal individuals and patients with an unrelated form of polycythaemia. They then measured how the lungs and hearts of these people reacted to mild hypoxia (similar to that experienced on commercial air flights) and moderate hypoxia (equiv alent to being on the top of an Alpine peak). They found that patients with Chuvash polycythaemia naturally breathe slightly quicker and deeper than normal individuals, and that their breathing rate increased dramatically and abnormally when oxygen was reduced. They also found that at normal oxygen levels the pulmonary blood vessels of these patients were more constricted than those of control individuals, and that they reacted more extremely to hypoxia. Similarly, the normal heart rate of the patients was slightly higher than that of the controls and increased much more in response to mild hypoxia. What Do These Findings Mean? The physiological differences measured by the researchers between Chuvash polycythaemia patients and control individuals are similar to the adaptations seen in people traveling to high altitudes where oxygen is limited. Thus, the VHL–HIF proteins may regulate the response to different oxygen concentrations both in individual cells and at the systemic level, although more physiological studies are needed to confirm this. Because the pulmonary blood vessels of patients with Chuvash polycythaemia are always abnormally constricted, and even more so when oxygen is limited, these people should avoid living at high altitude and should minimise air travel, suggest the researchers. The increased blood pressure in their lungs (pulmonary hypertension) could conceivably cause heart failure under such circumstances. Finally, this study has implications for the development of drugs directed at the VHL–HIF system. Agents are currently being designed to promote the development of new blood vessels after strokes or heart attacks by preventing the destruction of HIF, but based on the findings here such agents might have undesirable physiological affects. Conversely, HIF inhibitors (which act as anti-cancer reagents by increasing hypoxia in the centre of tumors and so inhibiting their growth) might be useful in the treatment of pulmonary hypertension. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030290. • Online Mendelian Inheritance in Man page on Chuvash polycythaemia • Information from the VHL Family Alliance on von Hippel–Lindau disease, including information on Chuvash polycythaemia • Wikipedia page on polycythaemia and von Hippel–Lindau disease (note: Wikipedia is a free online encyclopaedia that anyone can edit), Physiological study of patients with Chuvash polycythemia (caused by mutation of VHL) reveals characteristics similar to those associated with acclimatization to the hypoxia of high altitude.

The hypoxia-inducible factor (HIF) family of transcription factors is responsible for coordinating the cellular response to low oxygen levels in animals. By regulating the expression of a large array of target genes during hypoxia, these proteins also direct adaptive changes in the hematopoietic, cardiovascular, and respiratory systems. They also play roles in pathological processes, including tumorogenesis. In recent years, several oxygenases have been identified as key molecular oxygen sensors within the HIF system. The HIF hydroxylases regulate the stability and transcriptional activity of the HIF-alpha subunit by catalyzing hydroxylation of specific proline and asparaginyl residues, respectively. They require oxygen and 2-oxoglutarate (2OG) as co-substrates, and depend upon non-heme ferrous iron (Fe(II)) as a cofactor. This article summarizes current understanding of the biochemistry of the HIF hydroxylases, identifies targets for their pharmacological manipulation, and discusses their potential in the therapeutic manipulation of the HIF system.

Objective To validate the use of the International Prostate Symptom Score (IPSS) as a stand-alone tool to detect urethral stricture recurrence following urethroplasty. Materials and Methods This study included 393 men who had undergone anterior urethroplasty and were enrolled in a multi-institutional outcomes study. Data analyzed included pre- and post-operative answers to the IPSS in addition to findings from a same- day cystoscopy. IPSS from men found to have cystoscopic recurrence were then compared to scores from those with successful repairs, and receiver operating characteristic curves were plotted to illustrate the predictive ability of these questions to screen for cystoscopic recurrence. Results Mean postoperative scores were lower (fewer symptoms) in successful repairs; IPSS improved from preoperative values regardless of recurrence. Successful repairs had significantly better degree of improvement in question #5 (assessing weak stream) compared to recurrences. Receiver operating characteristic curves demonstrated the highest area under the curve for the IPSS quality of life question (0.66) that alone outperformed the complete IPSS questionnaire (0.56). Conclusion The IPSS had inadequate sensitivity and specificity to be used as a stand-alone screening tool for stricture recurrence in this large cohort of men, highlighting the need to continue development of a disease-specific, validated patient-reported outcome measure.

The past decade has seen significant changes in the training for all surgical residents.1 Residents are working fewer hours and spending less time in the operating rooms. Of the hours spent operating, a greater percentage of them are being focused on learning robotic and laparoscopic skills than ever before, especially in urology, as these are the skills often coveted by the private practice jobs being pursued by nearly 90% of graduates.2,3 This means that by default, less time will be spent during training performing complex open procedures. It is perhaps not surprising, that the decade has also seen an increase in fellowship training of all surgical subspecialties. Proposed reasons for this trend are many,4 but it has been postulated that with less operating room exposure, graduating residents are more commonly feeling they need more training before starting their careers.5 Until recently, few residents pursued formal postgraduate training in adult reconstructive urology, a specialty that performs many complex open procedures, but there are now 15 single-year positions available for postresidency training,6 prompting the Genitourinary Reconstructive Society to begin a formal matching process for reconstructive fellows beginning in the year 2013. As this fellowship becomes more formalized and learning objectives are outlined, it is important to better understand the scope of practice required of potential fellows upon fellowship graduation. The purpose of this study was to examine the early practice patterns of recently trained reconstructive fellows. We hypothesized that the practice patterns will vary widely depending on the respective fellows’ home institution, but that reconstructive procedures will make up a large percentage of their practice. Additionally, we hypothesized that with increased years in practice, the number and complexity of reconstructive cases will increase.

To our knowledge data on diagnostic angiography and angioembolization after renal trauma have been limited to single institution series with small numbers. We used the National Trauma Data Bank® to investigate national patterns of diagnostic angiography and angioembolization after blunt and penetrating renal trauma.All renal injuries treated between 2002 and 2007 were identified in the National Trauma Data Bank by Abbreviated Injury Scale codes and converted to American Association for the Surgery of Trauma renal injury grades. Diagnostic angiography and angioembolization were identified by ICD-9 codes and examined. Initial angioembolization was considered a failure if subsequent therapy was needed. Repeat diagnostic angiography was not considered a failure.A total of 9,002 renal injuries were available for analysis. A total of 165 patients (2%) underwent diagnostic angiography after renal injury, including 77 (47%) who underwent concomitant angioembolization. Of the patients 78% sustained grade III-V renal injuries. Of the 77 patients with initial angioembolization 68 required successive therapy. Repeat angioembolization was the most common management choice (29% of patients). Secondary angioembolization was durable during the index hospitalization with success in 35 of 36 cases. Successive therapy was required after initial angioembolization for all grade IV and V renal injuries in 48 patients. The overall renal salvage rate was 92%, including 88% for grade IV and V injuries.Successive therapy is common after initial management of renal injury by angioembolization. Close observation is highly recommended after initial angioembolization for grade IV-V renal injuries. National agreement on the use of diagnostic angiography and angioembolization is needed since these procedures may be overused after grade I-III renal injuries.

The hypoxia-inducible factors (HIFs; isoforms HIF-1α, HIF-2α, HIF-3α) mediate many responses to hypoxia. Their regulation is principally by oxygen-dependent degradation, which is initiated by hydroxylation of specific proline residues followed by binding of von Hippel-Lindau (VHL) protein. Chuvash polycythemia is a disorder with elevated HIF. It arises through germline homozygosity for hypomorphic VHL alleles and has a phenotype of hematological, cardiopulmonary, and metabolic abnormalities. This study explores the phenotype of two other HIF pathway diseases: classic VHL disease and HIF-2α gain-of-function mutation. No cardiopulmonary abnormalities were detected in classic VHL disease. HIF-2α gain-of-function mutations were associated with pulmonary hypertension, increased cardiac output, increased heart rate, and increased pulmonary ventilation relative to metabolism. Comparison of the HIF-2α gain-of-function responses with data from studies of Chuvash polycythemia suggested that other aspects of the Chuvash phenotype were diminished or absent. In classic VHL disease, patients are germline heterozygous for mutations in VHL, and the present results suggest that a single wild-type allele for VHL is sufficient to maintain normal cardiopulmonary function. The HIF-2α gain-of-function phenotype may be more limited than the Chuvash phenotype either because HIF-1α is not elevated in the former condition, or because other HIF-independent functions of VHL are perturbed in Chuvash polycythemia.—Formenti, F., Beer, P. A., Croft, Q. P. P., Dorrington, K. L., Gale, D. P., Lappin, T. R. J., Lucas, G. S., Maher, E. R., Maxwell, P. H., McMullin, M. F., O'Connor, D. F., Percy, M. J., Pugh, C. W., Ratcliffe, P. J., Smith, T. G., Talbot, N. P., Robbins, P. A. Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2α gain-of-function mutation.

The purpose of this study was to investigate the effect of a volunteer activity on the perceived well-being of long-term-care (LTC) residents. Residents from five LTC facilities were randomly assigned into either a mentoring or a usual-care control group. Residents in the mentoring group tutored conversational skills to English-as-a-second-language students on a one-on-one basis for 1 hour twice per week for 12 weeks. Well-being, as a global outcome construct, was measured at baseline, after intervention, and at 3-month follow-up using the Geriatric Depression Scale, Life Satisfaction Index–A, and a self-rated health question. After intervention, residents who participated in the mentoring group rated their level of well-being higher (p = .047) than those in the usual-care group on the basis of a multivariate nonparametric global statistical test. The positive effect of mentoring on well-being relative to the control was sustained at 3-month follow-up assessment (p = .029). Findings provide preliminary support for engaging LTC residents in volunteer mentoring activities to improve their well-being.

Formal systems of peer teaching are common in many advanced-degree graduate school programs but are less prevalent in medical schools. In 1997, The Medical University of South Carolina's Center for Academic Excellence created a Supplemental Instructor (SI) program in which interested upper-level medical students are hired to teach a small group of junior peers, primarily in basic science topics.The purpose of this study was to examine if participation as an SI leader resulted inmeasurable academic improvement for those students. This study examined if participation as a teacher in the SI program (SI leader) resulted in measurable academic improvement for those students.Admission characteristics (grade point average [GPA], Medical College Aptitude Test score, age, year of enrollment, and gender) of all SI leaders were compiled from the academic years 1996-2001. A second cohort of students, who shared the first group's admission characteristics but who chose not to teach as SIs, was identified as a comparison control group. Outcome measures included United States Medical Licensing Examination (USMLE) Step 1 and 2 scores and final medical school GPA. Paired student two-tailed t -test statistics compared group means on all outcome variables.There were 199 SI leaders with non-SI students matched controls studied. There were no significant differences upon admission between the two groups; however, the SI leader group had significantly higher USMLE Step 1 and Step 2 scores and final medical school GPA compared to the non-SI group.The activity of formal peer-teaching was beneficial to the SI leaders' own academic success as measured by GPA and USMLE test scores.

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.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.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).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.

© 2015 Elsevier Ltd. All rights reserved. Introduction: Most high-grade renal injuries (American Association for Surgery of Trauma (AAST) grades III-V) result from motor vehicle collisions associated with numerous concomitant injuries. Sports-related blunt renal injury tends to have a different mechanism, a solitary blow to the flank. We hypothesized that high-grade renal injury is often isolated in sports-related renal trauma. Material and methods: We identified patients with AAST grades III-V blunt renal injuries from four level 1 trauma centres across the United States between 1/2005 and 1/2014. Patients were divided into "Sport" or "Non-sport" related groups. Outcomes included rates of hypotension (systolic blood pressure 110 bpm), concomitant abdominal injury, and procedural/surgical intervention between sports and non-sports related injury. Results: 320 patients met study criteria. 18% (59) were sports-related injuries with the most common mechanisms being skiing, snowboarding and contact sports (25%, 25%, and 24%, respectively). Median age was 24 years for sports and 30 years for non-sports related renal injuries (p = 0.049). Males were more commonly involved in sports related injuries (85% vs. 72%, p = 0.011). Median injury severity score was lower for sports related injuries (10 vs. 27, p < 0.001). There was no difference in renal abbreviated injury scale scores. Sports related trauma was more likely to be isolated without other significant injury (69% vs. 39% (p < 0.001)). Haemodynamic instability was present in 40% and 51% of sports and non-sports renal injuries (p = 0.30). Sports injuries had lower transfusion (7% vs. 47%, p < 0.001) and lower mortality rates (0% vs. 6%, p = 0.004). There was no difference in renal-specific procedural interventions between the two groups (17% sports vs. 18% non-sports, p = 0.95). Conclusions: High-grade sports-related blunt renal trauma is more likely to occur in isolation without other abdominal or thoracic injuries and clinicians must have a high suspicion of renal injury with significant blows to the flank during sports activities.

Hepcidin inhibits iron uptake from the gut and release of iron from macrophages in the reticuloendothelial system. Suppression of plasma hepcidin occurs in lowlanders after ascent to high altitude, reflecting the increased iron demand for erythropoiesis, but the mechanism and primary stimulus for hepcidin suppression in this setting remains unclear...

Objectives Hydropneumothorax (HPTX) is recognized as a potential complication of percutaneous nephrostolithotomy (PCNL), particularly with supracostal access. Postoperative chest radiography (CXR) is routinely used to evaluate the chest after PCNL. We prospectively compared the sensitivity of intraoperative chest fluoroscopy with immediate postoperative portable CXR and postoperative day 1 chest computed tomography (CT) for the detection of pleural fluid. Methods A total of 89 consecutive patients (mean age 47.9 ± 13.3 years; 100 renal units) undergoing PCNL were prospectively evaluated with intraoperative fluoroscopy at the conclusion of the procedure and then with anteroposterior CXR in the postanesthesia care unit and postoperative day 1 noncontrast, thin-cut CT of the kidneys and lung bases. CT imaging of the lung bases comprised the reference standard for detecting pleural fluid. Results A total of 104 percutaneous renal accesses in 100 renal units, 60 above and 44 below the 12th rib, were used. In 16 cases (16%), a second-stage procedure was performed to clear residual stone fragments detected on post-PCNL CT. HPTX was detected in 1, 8, and 38 cases by initial fluoroscopy, immediate postoperative CXR, and CT scan, respectively. Intervention was necessary in 7 patients. In 2 patients with fluoroscopic evidence of pleural fluid (1 at the initial PCNL and 1 during second-look flexible nephroscopy), intraoperative pleural drainage was performed percutaneously. In the other 5 patients, intervention was determined by the size of the HPTX on chest CT scan (n = 1) or the presence of symptoms (n = 4). In no case was intervention performed on the basis of the immediate postoperative CXR findings when intraoperative chest fluoroscopy was negative. Conclusions Intraoperative chest fluoroscopy during PCNL is sufficient to detect clinically significant HPTXs, and, therefore, routine postoperative CXRs are not necessary. However, a high index of suspicion based on clinical symptoms postoperatively should prompt chest imaging.

Oxygen-dependent regulation of the erythropoietin gene is mediated by the hypoxia-inducible factor (HIF) family of transcription factors. When oxygen is plentiful, HIF undergoes hydroxylation by a family of oxygen-dependent prolyl hydroxylase domain (PHD) proteins, promoting its association with the von Hippel-Lindau (VHL) ubiquitin E3 ligase and subsequent proteosomal degradation. When oxygen is scarce, the PHD enzymes are inactivated, leading to HIF accumulation and upregulation not only of erythropoietin expression, but also the expression of hundreds of other genes, including those coordinating cardiovascular and ventilatory adaptation to hypoxia. Nevertheless, despite the identification of over 50 mutations in the PHD-HIF-VHL pathway in patients with previously unexplained congenital erythrocytosis, there are very few reports of associated cardiopulmonary abnormalities. We now report exaggerated pulmonary vascular and ventilatory responses to acute hypoxia in a 35-year-old man with erythrocytosis secondary to heterozygous mutation in PHD2, the most abundant of the PHD isoforms. We compare this phenotype with that reported in patients with the archetypal disorder of cellular oxygen sensing, Chuvash polycythemia, and discuss the possible clinical implications of our findings, particularly in the light of the emerging role for small molecule PHD inhibitors in clinical practice.

Injection of mitomycin C may increase the success of transurethral incision of the bladder neck for the treatment of bladder neck contracture. We evaluated the efficacy of mitomycin C injection across multiple institutions.Data on all patients who underwent transurethral incision of the bladder neck with mitomycin C from 2009 to 2014 were retrospectively reviewed from 6 centers in the TURNS. Patients with at least 3 months of cystoscopic followup were included in the analysis.A total of 66 patients underwent transurethral incision of the bladder neck with mitomycin C and 55 meeting the study inclusion criteria were analyzed. Mean ± SD patient age was 64 ± 7.6 years. Dilation or prior transurethral incision of the bladder neck failed in 80% (44 of 55) of patients. Overall 58% (32 of 55) of patients achieved resolution of bladder neck contracture after 1 transurethral incision of the bladder neck with mitomycin C at a median followup of 9.2 months (IQR 11.7). There were 23 patients who had recurrence at a median of 3.7 months (IQR 4.2), 15 who underwent repeat transurethral incision of the bladder neck with mitomycin C and 9 of 15 (60%) who were free of another recurrence at a median of 8.6 months (IQR 8.8), for an overall success rate of 75% (41 of 55). Incision with electrocautery (Collins knife) was predictive of success compared with cold knife incision (63% vs 50%, p=0.03). Four patients experienced serious adverse events related to mitomycin C and 3 needed or are planning cystectomy.The efficacy of intralesional injection of mitomycin C at transurethral incision of the bladder neck was lower than previously reported and was associated with a 7% rate of serious adverse events.

The authors of this guideline reviewed the urologic trauma literature to guide clinicians in the appropriate methods of evaluation and management of genitourinary injuries.A systematic review of the literature using the MEDLINE® and EMBASE databases (search dates 1/1/90-9/19/12) was conducted to identify peer-reviewed publications relevant to urotrauma. The review yielded an evidence base of 372 studies after application of inclusion/exclusion criteria. These publications were used to inform the statements presented in the guideline as Standards, Recommendations or Options. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate) or C (low). In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions.Guideline statements were created to inform clinicians on the initial observation, evaluation and subsequent management of renal, ureteral, bladder, urethral and genital traumatic injuries.Genitourinary organ salvage has become increasingly possible as a result of advances in imaging, minimally invasive techniques, and reconstructive surgery. As the field of genitourinary reconstruction continues to evolve, clinicians must strive to approach clinical problems in a creative, multidisciplinary, evidence-based manner to ensure optimal outcomes.

The National Highway Traffic Safety Administration's New Car Assessment Program (NCAP) implemented side-impact crash testing on all new vehicles since 1998 to assess the likelihood of major thoracoabdominal injuries during a side-impact crash. Higher crash test rating is intended to indicate a safer car, but the real-world applicability of these ratings is unknown. Our objective was to determine the relationship between a vehicle's NCAP side-impact crash test rating and the risk of major thoracoabdominal injury among the vehicle's occupants in real-world side-impact motor vehicle crashes.The National Automotive Sampling System Crashworthiness Data System contains detailed crash and injury data in a sample of major crashes in the United States. For model years 1998 to 2010 and crash years 1999 to 2010, 68,124 occupants were identified in the Crashworthiness Data System database. Because 47% of cases were missing crash severity (ΔV), multiple imputation was used to estimate the missing values. The primary predictor of interest was the occupant vehicle's NCAP side-impact crash test rating, and the outcome of interest was the presence of major (Abbreviated Injury Scale [AIS] score ≥ 3) thoracoabdominal injury.In multivariate analysis, increasing NCAP crash test rating was associated with lower likelihood of major thoracoabdominal injury at high (odds ratio [OR], 0.8; 95% confidence interval [CI], 0.7-0.9; p0.01) and medium (OR, 0.9; 95% CI, 0.8-1.0; p0.05) crash severity (ΔV), but not at low ΔV (OR, 0.95; 95% CI, 0.8-1.2; p = 0.55). In our model, older age and absence of seat belt use were associated with greater likelihood of major thoracoabdominal injury at low and medium ΔV (p0.001), but not at high ΔV (p ≥ 0.09).Among adults in model year 1998 to 2010 vehicles involved in medium and high severity motor vehicle crashes, a higher NCAP side-impact crash test rating is associated with a lower likelihood of major thoracoabdominal trauma.Epidemiologic study, level III.

Objective To evaluate the short- to medium-term outcomes after artificial urinary sphincter (AUS) placement from a large, multi-institutional, prospective, follow-up study. We hypothesize that along with radiation, patients with any history of a direct surgery to the urethra will have higher rates of eventual AUS explantation for erosion and/or infection. Materials and Methods A prospective outcome analysis was performed on 386 patients treated with AUS placement from April 2009 to December 2012 at 8 institutions with at least 3 months of follow-up. Charts were analyzed for preoperative risk factors and postoperative complications requiring explantation. Results Approximately 50% of patients were considered high risk. High risk was defined as patients having undergone radiation therapy, urethroplasty, multiple treatments for bladder neck contracture or urethral stricture, urethral stent placement, or a history of erosion or infection in a previous AUS. A total of 31 explantations (8.03%) were performed during the follow-up period. Overall explantation rates were higher in those with prior radiation and prior UroLume. Men with prior AUS infection or erosion also had a trend for higher rates of subsequent explantation. Men receiving 3.5-cm cuffs had significantly higher explantation rates than those receiving larger cuffs. Conclusion This outcomes study confirms that urethral risk factors, including radiation history, prior AUS erosion, and a history of urethral stent placement, increase the risk of AUS explantation in short-term follow-up.

The traditional American Association for the Surgery of Trauma (AAST) grading of renal injury does not adequately identify the subset of patients who are most likely to require intervention for bleeding. Recently, several high-risk criteria (HRC) for bleeding after renal injury were identified, and we sought to externally validate these criteria among patients with grade 4 renal injury.All patients presenting to a level I trauma center with blunt grade 4 renal injuries from 2003 to 2010 were reviewed, and stage was determined by the 1989 AAST staging criteria. Dependent variables included the presence of a hilar injury or any of the HRC (perirenal hematoma size, intravascular contrast extravasation, and medial or complex laceration). The primary outcome was the need for intervention (renorrhaphy, nephrectomy, or angiography) for hemodynamic instability.A total of 84 patients with grade 4 renal lacerations were identified. Two or more HRC were present in 18 patients (21%), and intervention for hemodynamic instability was performed in 14 patients (17%). Compared with patients with 0 or 1 HRC, those with ≥ 2 HRC were approximately 25 times more likely to require intervention for hemodynamic instability (odds ratio [OR]24.9, 95% CI 5.5 to 112.9, p0.001). Patients with no HRC were unlikely to require intervention for hemodynamic instability.Among patients with blunt grade 4 renal injury, the presence of ≥ 2 HRC effectively predicts the need for intervention for hemodynamic instability and can be used to identify patients who require intensive monitoring. The AAST grading system for renal injury should be modified to better reflect injury severity.

Dexamethasone ameliorates the severity of acute mountain sickness (AMS) but it is unknown whether it obtunds normal physiological responses to hypoxia. We studied whether dexamethasone enhanced or inhibited the ventilatory, cardiovascular, and pulmonary vascular responses to sustained (8 h) hypoxia. Eight healthy volunteers were studied, each on four separate occasions, permitting four different protocols. These were: dexamethasone (20 mg orally) beginning 2 h before a control period of 8 h of air breathing; dexamethasone with 8 h of isocapnic hypoxia (end-tidal Po2 = 50 Torr); placebo with 8 h of air breathing; and placebo with 8 h of isocapnic hypoxia. Before and after each protocol, the following were determined under both euoxic and hypoxic conditions: ventilation; pulmonary artery pressure (estimated using echocardiography to assess maximum tricuspid pressure difference); heart rate; and cardiac output. Plasma concentrations of erythropoietin (EPO) were also determined. Dexamethasone had no early (2-h) effect on any variable. Both dexamethasone and 8 h of hypoxia increased euoxic values of ventilation, pulmonary artery pressure, and heart rate, together with the ventilatory sensitivity to acute hypoxia. These effects were independent and additive. Eight hours of hypoxia, but not dexamethasone, increased the sensitivity of pulmonary artery pressure to acute hypoxia. Dexamethasone, but not 8 h of hypoxia, increased both cardiac output and systemic arterial pressure. Dexamethasone abolished the rise in EPO induced by 8 h of hypoxia. In summary, dexamethasone enhances ventilatory acclimatization to hypoxia. Thus, dexamethasone in AMS may improve oxygenation and thereby indirectly lower pulmonary artery pressure.

BACKGROUND: It has recently been shown that commercial air travel triggers hypoxic pulmonary vasoconstriction and modestly increases pulmonary artery pressure in healthy passengers. There is large interindividual variation in hypoxic pulmonary vasoreactivity, and some passengers may be at risk of developing flight-induced pulmonary hypertension, with potentially dangerous consequences. This study sought to determine whether it is possible for a susceptible passenger to develop pulmonary hypertension in response to a routine commercial flight. CASE REPORT: Using in-flight echocardiography, a passenger was studied during a 6-h commercial flight from London to Dubai. The passenger was generally well and frequently traveled by air, but had been diagnosed with Chuvash polycythemia, a genetic condition that is associated with increased hypoxic pulmonary vasoreactivity. Hematocrit had been normalized with regular venesection. During the flight, arterial oxygen saturation fell to a minimum of 96% and systolic pulmonary artery pressure (sPAP) rapidly increased into the pulmonary hypertensive range. The in-flight increase in sPAP was 50%, reaching a peak of 45 mmHg. DISCUSSION: This study has established that an asymptomatic but susceptible passenger can rapidly develop in-flight pulmonary hypertension even during a medium-haul flight. Prospective passengers at risk from such responses, including those who have cardiopulmonary disease or increased hypoxic pulmonary vasoreactivity, could benefit from preflight evaluation with a hypoxia altitude simulation test combined with simultaneous echocardiography (HAST-echo). The use of in-flight supplementary oxygen should be considered for susceptible individuals, including all patients diagnosed with Chuvash polycythemia.

Summary Introduction Some children who sustain high-grade blunt renal injury may require operative intervention. In the present study, it was hypothesized that there are computed tomography (CT) characteristics that can identify which of these children are most likely to need operative intervention. Materials and methods A retrospective review was performed of all pediatric blunt renal trauma patients at a single level-I trauma center from 1990 to 2015. Inclusion criteria were: children with American Association for the Surgery of Trauma (AAST) Grade-IV or V renal injuries, aged ≤18 years, and having available CT images with delayed cuts. The CTs were regraded according to the revised AAST grading system proposed by Buckley and McAninch in 2011. Radiographic characteristics of renal injury were correlated with the primary outcome of any operative intervention: ureteral stent, angiography, nephrectomy/renorrhaphy, and percutaneous nephrostomy/drain. Results One patient had a Grade-V injury and 26 patients had Grade-IV injuries. Nine patients (33.3%) underwent operative interventions. Patients in the operative intervention cohort were more likely to manifest a collecting system filling defect (P = 0.040) ( Fig. A) and lacked ureteral opacification (P = 0.010). The CT characteristics, including percentage of devascularized parenchyma, medial contrast extravasation, intravascular contrast extravasation, perirenal hematoma distance and laceration location, were not statistically significant. Of the 21 patients who had a collecting system injury, eight (38.1%) needed ureteral stents. Renorrhaphy was necessary for one patient. Although the first operative intervention occurred at a median of hospital day 1 (range 0.5–2.5), additional operative interventions occurred from day 4–16. Thus, it is prudent to closely follow-up these patients for the first month after injury. Two patients with complex renal injuries had an accessory renal artery resulting in well-perfused upper and lower pole fragments, and were managed nonoperatively without readmission ( Fig. B). Conclusions Collecting system defects and lack of ureteral opacification were significantly associated with failure of nonoperative management. A multicenter trial is needed to confirm these findings and whether nonsignificant CT findings are associated with operative intervention. In the month after renal injury, these patients should be mindful of any changes in symptoms, and maintain a low index of suspicion for an emergency room visit. For the physician, close follow-up and appropriate counseling of these high-risk patients is advised. Download : Download high-res image (175KB) Download : Download full-size image Figure . A. Axial CT image demonstrating left renal pelvis extravasation and collecting system filling defect (blue arrow). B. Coronal CT image demonstrating dual arterial supply of right kidney with lower pole accessory artery (*) and well-perfused upper and lower pole fragments. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Dear Editor, We read with interest the case reported by Weber-Carstens et al. [1] of a woman with longstanding idiopathic pulmonary arterial hypertension who presented with severe polytrauma. Her admission was complicated by critical hypoxia and severe acute-onchronic pulmonary hypertension resulting in acute right heart decompensation. During this life-threatening phase, the authors report that the benefits of standard combination therapy in reducing right ventricular afterload were short-lived in the face of worsening hypoxia. Recent work from our group and others has introduced the possibility that intravenous iron may provide additional benefit in this setting. In healthy iron-replete men studied over 1 week at high altitude (equivalent to sea level FiO2 *0.12) we found that established hypoxiainduced pulmonary hypertension was significantly reversed by a single 200 mg dose of intravenous iron sucrose [2]. This effect was evident within 4 h of infusion—rapid enough to be of possible benefit in offloading the right ventricle in the acute clinical setting. We also studied patients with chronic mountain sickness over 1 month at high altitude and found that depletion of iron by venesection was associated with worsening pulmonary hypertension despite a large reduction in haematocrit (although this effect was not immediately reversed by subsequent iron infusions) [2]. This work was preceded by an 8-h laboratory study of healthy ironreplete volunteers in which the increase in pulmonary arterial pressure caused by hypoxia was blunted by prior intravenous infusion of iron sucrose (200 mg), while the pulmonary vascular response to hypoxia was enhanced by reduction of iron availability with desferrioxamine [3]. The dose of iron used in these studies is small relative to total body iron stores (approximately 4 g), and current intravenous formulations such as iron sucrose are very safe. These studies indicate that hypoxic pulmonary hypertension can be attenuated by increasing iron availability and exacerbated by decreasing iron availability. This interaction between iron, hypoxia and the pulmonary circulation is consistent with known effects of iron on the hypoxiainducible factor (HIF) family of transcription factors and involvement of HIF in regulating cardiopulmonary physiology [2–4]. Studies from several centres have subsequently confirmed a link between iron status and idiopathic pulmonary arterial hypertension, demonstrating that iron deficiency is unexpectedly common in this disease and independently worsens morbidity and mortality (recently reviewed by Rhodes et al. [5]). Two European studies investigating the use of intravenous iron in pulmonary arterial hypertension are now underway [5]. We look forward to the results of these and other studies. In the meantime, the available evidence raises the possibility that intravenous iron may be beneficial as a rescue therapy when hypoxia and pulmonary hypertension are acutely life-threatening and conventional treatment is inadequate.