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Background: Socioeconomic differences are present within the population of men who experience infertility and seek treatment., Objective: To study the association of socioeconomic status with semen parameters in a group of men using mail-in semen analyses., Materials and Methods: The records of 11,134 men that used mail-in semen analyses from a fertility company were identified. Their demographic information, semen parameters, and ZIP codes were collected. Area deprivation index (ADI) was used as a proxy for socioeconomic status and was calculated for each individual using their ZIP codes in order to measure their level of socioeconomic deprivation. A higher ADI signifies a more deprived area. The association between ADI and the semen parameters of this group was measured using linear regression analysis adjusted for age., Results: 11,134 men were included in the study with a median age of 35 years (interquartile range (IQR): 32-40) and a median ADI of 83 (IQR: 68-97). The cohort had a median sperm concentration of 31 million/mL (IQR: 14-59), median total sperm count of 123 million (IQR: 57-224), median total motile sperm of 35 million (IQR: 9-95), median total motility of 32% (IQR: 15-52), progressive motility of 22% (IQR: 9-38), and morphology percent normal of 4% (IQR: 2-7). Higher ADI, indicating lower socioeconomic status, was negatively associated with various semen parameters, including sperm concentration, total sperm count, total motile sperm, and total and progressive motility., Discussion and Conclusion: Men who live in more deprived areas are more likely to have worse semen parameters. Further research is needed to thoroughly examine the impact of socioeconomic status on male fertility. A comprehensive approach that targets upstream social, economic, and healthcare factors can possibly alleviate the negative association of socioeconomic status with fertility and semen parameters., (© 2024 American Society of Andrology and European Academy of Andrology.)

Objective: To evaluate plaintiff and defendant characteristics associated with iatrogenic genitourinary (GU) trauma litigation and outcomes of closed claims., Methods: LexisNexis was queried in April 2023 using terms related to GU organs and injury, and manually reviewed for iatrogenic cases. Case details including defendant, organ involvement, and legal outcome were obtained. Multinomial regression analysis was performed to identify factors associated with outcome., Results: Four hundred ten cases involving 611 defendants were identified, with the ureter the most commonly affected organ (202/410, 49.3%). Most cases involved adult plaintiffs (380, 92.7%) and resulted in favor of the defense (227, 55.4%). Injuries resulted most frequently from gynecologic surgeries (179, 43.7%). Defendants were most commonly obstetricians/gynecologists (243/611, 39.8%) and urologists (168, 27.5%). Penile (OR 6.3 [95% CI 2.5-16.1]) and urethral (OR 4.8 [2.0-11.7]) injuries were associated with greater odds of a plaintiff verdict relative to ureter injury. A plaintiff verdict was also more likely when defendants were academic hospitals compared to individual practitioners (OR 4.3 [1.9-9.9]). In cases ruling in favor of the plaintiff, indemnity payments were larger when the defendants were comprised of individual practitioners compared to a hospital or medical group (median $549,613 vs $250,000, P <.001)., Conclusion: Urologists may be involved in medical malpractice lawsuits for iatrogenic injury even when they are uninvolved in the index procedure. Most cases that reach litigation result in defense verdicts regardless of the GU organ injured. Defendant characteristics associated with plaintiff verdicts are more nuanced, and providers should be aware of potential downstream effects of litigation., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The American Urological Association and Endocrine Society published guidelines for the management of testosterone deficiency in 2018. Testosterone prescription patterns have varied widely recently, owing to increased public interest and emerging data on the safety of testosterone therapy. The effect of guideline publication on testosterone prescribing is unknown. Thus, we aimed to assess testosterone prescription trends using Medicare prescriber data. Specialties with over 100 testosterone prescribers from 2016-2019 were analyzed. Nine specialties were included (in order of descending prescription frequency): family practice, internal medicine, urology, endocrinology, nurse practitioners, physician assistants, general practice, infectious disease, and emergency medicine. The number of prescribers grew by a mean of 8.8% annually. There was a significant increase in average claims per provider from 2016 to 2019 (26.4 to 28.7, p < 0.0001), with the steepest increase occurring between 2017 and 2018 when the guidelines were released (27.2 to 28.1, p = 0.015). The largest increase in claims per provider was among urologists. Advanced practice providers comprised 7.5% of Medicare testosterone claims in 2016 and 11.6% in 2019. While no causation can be established, these results suggest that professional society guidelines are associated with increasing numbers of testosterone claims per provider, especially among urologists. The changing demographics of prescribers justifies targeted education and further research., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To assess efficacy, comfort, and symptoms of a novel ureteral stent (RELIEF) substituting the distal semirigid coil of a traditional double-J for a floating, monofilament tether allowing coaptation of the ureteral orifice. Ureteral instrumentation notoriously cause discomfort, urgency, frequency, dysuria, and hematuria; prolonged morbidity is likely related to stent-associated vesicoureteral reflux (VUR). We hypothesized this design would eliminate VUR, be safe and provide comfort following intervention., Methods: Twenty-eight patients within a single institution were enrolled. Passive cystography was performed pre- and post-stent placement assessing VUR. Patients completed Ureteric Stent Symptoms Questionnaires (USSQ) before placement (baseline), postop day 1, and day of removal., Results: Twenty RELIEF stents were placed (11 female and 9 male). 95% demonstrated no VUR following placement. No unexpected adverse complications occurred; 1 patient opted for early stent removal for significant discomfort. Average total USSQ scores demonstrated statistically significant improvement between first and third surveys (P < .001). Statistically significant improvement in body pain, general health, and work performance scores were noted as well (P < .05)., Conclusion: The RELIEF stent eliminates VUR with similar stent-related morbidity and overall well-tolerance. RELIEF-associated USSQ scores were below published mean symptom scores for standard double-J stents and appear safe in this preliminary clinical trial., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Due to the historic lack of transparency in healthcare pricing in the United States, the degree of price variation for vasectomy is largely unknown. Our study aims to assess characteristics of hospitals reporting prices for vasectomy as well as price variation associated with hospital factors and insurance status. A cross-sectional analysis was performed in October, 2022 using the Turquoise Database which compiles publicly available hospital pricing data. The database was queried for vasectomy prices to identify the cash (paid by patients not using insurance), commercial (negotiated by private insurers) and Medicare and Medicaid prices for vasectomies. Hospital characteristics of those that reported a price for vasectomy and those that did not were compared and pricing differences based on hospital ownership and reimbursement source were determined using multivariable linear regression analysis. Overall, only 24.7% (1657/6700) of hospitals reported a price for vasectomy. Those that reported a price had more beds (median 117 vs 80, p < 0.001), more physicians (median 1745 vs 1275, p < 0.001). They were also more likely to be nonprofit hospitals (77% vs 14%, p < 0.001) and to be in well-resourced areas (ADI 91.7 vs 94.4, p < 0.001). Both commercial prices and cash prices for vasectomy were lower at nonprofit hospitals than at for-profit hospitals (commercial: $1959.47 vs $2861.56, p < 0.001; cash: $1429.74 vs $3185.37, p < 0.001). Our study highlights the current state of pricing transparency for vasectomy in the United States. Patients may be counseled to consider seeking vasectomy at a nonprofit hospital to reduce their costs, especially when paying with cash. These findings also suggest a need for new policies to target areas with decreased price transparency to reduce price disparities., (© 2024. The Author(s).)

Objective: Current literature demonstrates low rates of compliance with postvasectomy semen analysis (PVSA). This study sought to determine factors that correlate with noncompliance with PVSA., Methods: A retrospective chart review was conducted for patients who underwent vasectomy within our institution. ArcGIS was used to securely calculate the shortest driving time from each patient's home to the single PVSA drop-off site. Kruskal-Wallis and chi-square tests analyzed characteristics of patients who did and did not submit PVSA samples, and odds ratios were calculated via multivariable logistic regression., Results: Overall, 515 of 850 patients met inclusion criteria and 219 (42.5%) of these had no recorded PVSA. Of those with a PVSA, 59% were completed within 16 weeks. Compliance with PVSA was associated with a shorter median driving time (30.6 minutes vs 34.2 minutes), more vasectomy in the operating room (19% vs 10%), and attending a follow-up appointment (40% vs 17%) (P < .005 for all). Age at vasectomy, race, ethnicity, BMI, paternity, and location of preoperative consultation did not significantly differ between the groups. Each 30 minutes of driving time was associated with a 48% reduction in the odds of a patient submitting PVSA at any time (OR 0.52 [0.37, 0.73])., Conclusion: As driving time to a drop-off center appears to be a significant barrier to PVSA compliance, providers should consider alternative collection methods such as at-home or in-office semen analysis., Competing Interests: Declaration of Competing Interest The authors have no relevant conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To assess the feasibility and safety of delayed primary closure (DPC) in Fournier's gangrene (FG) patients with large genital defects., Methods: A single institution retrospective review was performed from October 2020 to December 2022 of adult males that underwent DPC for FG. All patients underwent standard medical management and were assessed for DPC eligibility by the urology service. Clinical data on patient factors and outcomes were collected, and descriptive statistics were assessed., Results: Of 16 patients that underwent DPC, the average age was 61.1years and body mass index was 34.6 kg/m 2 . Median Charlson Comorbidity Index was 3.5 (IQR 2-5.3) and Fournier's Gangrene Severity Index was 6.5 (IQR 4.8-8). Median number of debridements was 2.5 (IQR 2-3), with a time to closure of 6.5days (IQR 3-11) and length of stay of 13days (IQR 9-16.3). Mean genital defect size was 119 cm 2 (range 44-346 cm 2 ). Eight patients (50%) were closed using scrotal flaps alone while other patients had advancement flaps using the inner thigh, lower abdomen, and perineum. The majority of patients were discharged home directly (63%). There were four Clavien-Dindo III complications: two partial flap necrosis, one wound dehiscence, and one instance of bleeding. Of patients with follow-up, 6/15 (40.0%) had no known complications., Conclusion: DPC is safe and effective for a range of patients presenting with FG. Patients with large defects may benefit from less complex wound management and direct discharge home., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To describe the racial and socioeconomic characteristics of men using mail-in semen testing kits for their fertility care in the United States over 3 years., Methods: A cross-sectional analysis was conducted of men who used mail-in semen analyses from a single direct-to-consumer (DTC) fertility platform between 2020 and 2022. Age, race/ethnicity, place of residence, and education level of men using mail-in semen analysis kits was collected from user questionnaires. Zip code level socioeconomic status was estimated using the Area Deprivation Index (ADI). These characteristics were compared to the overall population of the United States., Results: 4342 men used mail-in semen analyses from a single DTC fertility company between 2020 and 2022 and completed the questionnaire. The median age of this cohort was 36 (IQR: 32,40) years. The group consisted of predominantly white men (72%), with 7.9% Asian and only 5.1% Black, 3.2% Hispanic, 0.4% Indian American, 0.1% pacific islander, 5.8% mixed race, and 2.8% other groups. 45.8% of the group had completed college, 22% had a master's degree, and 9% had a doctoral degree. The mean ADI was 83.47 (SD 21.44) compared to the average ADI of 100 for the general US population (P < .005)., Conclusion: DTC mail-in semen analyses have the potential to improve access to affordable fertility care. Racial and ethnic minorities and lower socioeconomic classes are underrepresented for men seeking DTC fertility testing as they are for men presenting for in-office fertility care. Additional studies are needed to determine the factors responsible for these discrepancies., Competing Interests: Declaration of Competing Interest Ramy Abou Ghayda is the chief medical officer of Give Legacy. Give Legacy Inc. did not intervene nor influence the design, outcomes, materials, methods, or results of this manuscript. All the other authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The impact of ejaculatory abstinence on semen parameters using in-office semen analyses has been well-established; however, their variability has not been evaluated in men using mail-in semen analysis kits. Our study aims to describe how the sperm parameters using mail-in semen analysis tests change with abstinence and validate their equivalence to those seen with in-office semen analysis tests. We retrospectively reviewed the semen analysis results of men using mail-in semen analysis tests provided by Give Legacy, Inc (Legacy) facilities from 2019 to 2021. We collected their demographic information, abstinence duration, and semen parameters (conventional and kinematic) from their records. Semen samples were categorized as normozoospermic and oligozoospermic based on concentration. The shape of the relationship between abstinence duration and semen parameters was assessed via generalized additive models. We have collected 3,469 unique samples provided by 2,609 (75%) normozoospermic men and 860 (25%) oligozoospermic from all over the United States. In normozoospermic men, longer periods of sexual abstinence were linked to higher levels of sperm concentration, total sperm count, and total motile sperm. However, there was a decline in both total and progressive motility. Conversely, in oligozoospermic men, extended periods of abstinence led to a rapid decline in total motile sperm, as well as total and progressive motility. There was no significant correlation observed between sexual abstinence and variations in sperm morphology. Our study shows that variability of sperm parameters with abstinence, as measured through mail-in semen analysis tests, is comparable to the patterns observed with conventional in-office sperm testing.

Patients may turn to social media websites, such as Reddit, for information on erectile dysfunction prior to seeking care from a physician. We sought to identify, characterize, and assess the quality of the erectile dysfunction treatments discussed on the highly influential Reddit website. We assessed 2634 comments from two subreddits, r/AskMen and r/ErectileDysfunction, for positive and negative statements regarding treatments for erectile dysfunction. A total of 45 unique treatments were discussed and consisted of changes in sexual behavior (30%), lifestyle changes (29%), medical interventions (23%), talking with a partner about ED (10%), and use of supplements (8%). Only 24.4% of all treatments discussed are in line with current American Urological Association guidelines. Only 43.8% of all positive statements made endorsed a guidelines-based treatment, indicating a high rate of self-proclaimed success with alternative therapies. Our results indicate that there is active discussion of erectile dysfunction treatment on Reddit with a wide range of therapies recommended, however, the majority of the recommendations are not supported by strong clinical evidence., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To project the number and proportion of women in the urology workforce using recent demographic trends and develop an app to explore updated projections using future data., Methods: Demographic data were obtained from AUA Censuses and ACGME Data Resource Books. The proportion of female graduating urology residents was characterized with a logistic growth model. "Stock and Flow" models were used to project future population numbers and proportions of female practicing urologists, accounting for trainee demographics, retirement trends, and growth in the field., Results: Assuming growth in urology graduate numbers and continued logistic growth in the proportion of women, 10,957 practicing urologists (38%) will be female by 2062. If the rate of women entering urology residency stagnates, 7038 urologists (24%) will be female. If the retirement rates for women in urology change to mirror those of men and the proportion of female residents continues to experience logistic growth, 11,178 urologists (38%) will be female. An interactive app was designed to allow for a range of assumptions and future data: https://stephenrho.shinyapps.io/uro-workforce/., Conclusion: Workforce projections should incorporate recent growth in numbers of female residents. If current growth continues, 38% of urologists will be female by 2062. The app allows for exploration of different scenarios and can be updated with new data. The projections demonstrate the need for targeted efforts to recruit women into urology, address disparities within the field, and work toward retaining female urologists. We must continue working toward an equitable future workforce that can address the impending shortage of urologists., Competing Interests: DECLARATION OF COMPETING INTEREST None Declared., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Gender-affirming surgery leads to high satisfaction for patients; however, patients often require revision surgery. Revision labiaplasty is one of the most common surgeries following vaginoplasty. The labia minora commonly become incorporated into the labia majora and lose definition even after revision leading to patient dissatisfaction., Description of Technique: We propose a technique of incorporating cadaveric costal cartilage allograft into the revised labia minora to increase the definition., Patient and Methods: The procedure was demonstrated in a 38-year-old MTF patient who had previously undergone inversion vaginoplasty. The cartilage allograft was incorporated within the labia minora flaps dur ing labiaplasty., Results: The patient had lasting definition of her labia minora post-operatively at 6 weeks without adverse effects., Conclusion: We believe that this technique may be effective and safe in patients requesting more defined labia minora after vaginoplasty.

Testosterone deficiency is known to affect men with increasing incidence throughout their lifespan. The clinical manifestations of testosterone deficiency, in turn, negatively impact men's quality of life and perception of overall health. The interaction of chronic systemic disease and androgen deficiency represent an area for potential intervention. Here, we explore the topic of testosterone deficiency amongst men with end-stage organ failure requiring transplantation in order to elucidate the underlying pathophysiology of androgen deficiency of chronic disease and discuss whether intervention, including testosterone replacement and organ transplantation, improve patients' outcomes and quality of life., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Direct-to-consumer telemedicine platforms have expanded their reach to include services for the evaluation and treatment of testosterone deficiency., Aim: We aim to (i) evaluate the treatment practices and costs associated with receiving testosterone therapy through direct-to-consumer telemedicine platforms; (ii) compare these practices to the American Urological Association guidelines; and (iii) compare the cost of receiving similar care at a tertiary center., Methods: Google was queried to identify telemedicine platforms offing testosterone therapy. Websites were analyzed for information regarding the initial consultation, initial laboratory evaluation, follow up, treatment monitoring regimen, and associated costs of receiving testosterone therapy. The costs for similar services at a tertiary care center were estimated using a single institution's online cost estimator for a patient with no insurance, private insurance, or Medicare., Outcomes: Evaluation and treatment practices of each platform were compared to the American Urological Association guidelines, and a cost analysis was completed for the cost of (i) undergoing an initial evaluation, and (ii) receiving 12 months of treatment through each platform and at a tertiary center., Results: Three online platforms met inclusion criteria: Hone, Regenex Health, and TRT Nation. The initial evaluation and follow up of patients on TTh were similar between the online platforms and practice guidelines. The costs of the initial consultation were lowest for the patient with Medicare at a tertiary center and via the telemedicine platforms. Conversely, the cost of 12 months of intramuscular testosterone treatment was highest via the telemedicine platforms, ranging from $1,586 to $4,200, as compared to the tertiary center, which ranged from $134.01 to $1,333.04 with varying insurance models. Costs of ongoing treatment with transdermal testosterone are similarly higher via DTC platforms., Clinical Implications: Patients with private insurance or Medicare should be counseled that ongoing treatment through telemedicine platforms will likely incur a greater cost than receiving such care at a tertiary center that can utilize insurance coverage., Strengths & Limitations: Practice and cost comparisons include accurate, up-to-date information based on each platform's website. Limitations include the analysis of only three telemedicine platforms, and the ability to describe only the information provided on each website. In addition, cost estimates for the tertiary center only include a single type of private and public insurance, limiting generalizability., Conclusion: This observational study indicates that direct-to-consumer telemedicine platforms are largely following practice guidelines in the evaluation and treatment of testosterone, however, there is a high cost associated with ongoing treatment. Jesse E, Sellke N, Rivero M-J, et al. Practice Comparison and Cost Analysis of Direct-to-Consumer Telemedicine Platforms Offering Testosterone Therapy. J Sex Med 2022;19:1608-1615., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: To highlight and review encouraging preliminary studies behind several alternative products and interventions for erectile dysfunction (ED)., Recent Findings: Alternative treatments for ED are becoming more prevalent with increased consumer interest. "Natural" products are sold online, and numerous clinics offer various off-label and investigational interventions. These alternative treatments have demonstrated varying degrees of efficacy in randomized trials and meta-analyses, but none of these interventions has robust enough evidence to be considered first-line therapy. These treatments may find a role in combination with guideline treatments or may be used in novel penile rehabilitation research protocols. With growing interest in alternative treatment for men's health, an awareness of the literature is imperative for patient counsel. Alternative treatments, like L-arginine, have a growing body of evidence for efficacy in combination with PDE5i, and low-intensity shock wave therapy and stem cell therapy continue to demonstrate encouraging outcomes in ED trials.

Objective: Cardioplegic arrest (CP) and cardiopulmonary bypass (CPB) are associated with vasomotor dysfunction of coronary arterioles in patients with diabetes (DM) undergoing cardiac surgery. We hypothesized that DM may up-regulate vasopressin receptor expression and alter the contractile response of coronary arterioles to vasopressin in the setting of CP/CPB., Methods: Right atrial tissue samples of patients with DM and without (ND) (n = 8 in each group) undergoing cardiac surgery were harvested before and after CP/CPB. The isolated coronary arterioles (80-150 μm) dissected from the harvested right atrial tissue samples were cannulated and pressurized (40 mm Hg) in a no-flow state. The changes in diameter were measured with video microscopy. The protein expression/localization of vasopressin 1A receptors (V1A) and vasopressin 1B receptors (V1B) in the atrial tissue were measured by immune-blotting and immunohistochemistry., Results: The pre-CP/CPB contractile responses of the coronary arterioles to vasopressin were significantly increased post-CP/CPB in both the ND and DM groups. This effect was more pronounced in the vessels from patients in the DM group than that of vessels from patients in the ND group (P < .05). Vasopressin-induced contractile response of the coronary arterioles was inhibited in the presence of the specific V1A antagonist SR 49059 (10 -7  M) in both ND and DM vessels (P < .05). The post-CP/CPB protein levels of V1A were significantly increased compared with pre-CP/CPB values in both the ND and DM groups (P < .05), whereas this increase was greater in DM than that of ND (P < .05). Immunohistochemistry staining further indicates that V1B were mainly expressed in the myocardium but not in vascular smooth muscle., Conclusions: CP/CPB and DM are both associated with up-regulation in V1 receptor expression/localization in human myocardium. Vasopressin may induce coronary arteriolar constriction via V1A. This alteration may lead to increased coronary arteriolar spasm in patients with DM undergoing CP/CPB and cardiac surgery., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: We have previously found that hyperkalemic cardioplegic arrest in the setting of cardiopulmonary bypass (CP/CPB) is associated with impairment of the coronary arteriolar response to phenylephrine in nondiabetic (ND) patients. We hypothesized that diabetes may alter coronary arteriolar response to alpha-1 adrenergic agonist in the setting of CP/CPB. In this study, we further investigated the effects of diabetes on the altered coronary arteriolar response to phenylephrine in patients undergoing cardiac surgery., Methods: Coronary arterioles (90-150 μm in diameter) were harvested pre- and post-CP/CPB from the ND and diabetic mellitus (DM) patients (n = 8/group) undergoing cardiac surgery. In-vitro microvascular reactivity was examined in response to phenylephrine. The protein expression/localization of the alpha-1 adrenergic receptors in the atrial myocardium was measured by Western blotting and immunohistochemistry., Results: Phenylephrine (10 -9 to 10 -4  M) induced a dose-dependent contractile response in both ND and DM vessels pre- and post-CP/CPB. There was no significant difference in the pre-CP/CPB contractile responses to phenylephrine between ND and DM groups. The post-CP/CPB contractile response was significantly diminished in both ND and DM groups compared with the respective pre-CP/CPB response (P < 0.05 versus pre-CP/CPB). This diminished contractile response was more pronounced in vessels from DM patients compared with vessels from ND patients (P < 0.05 versus ND). There were no significant differences in the protein expression of alpha-1A and alpha-1B receptors in the atrial myocardium between the ND and DM groups or tissue harvested pre- or post-CP/CPB., Conclusions: Diabetes is associated with a decreased contractile response of coronary arterioles to phenylephrine in the setting of CP/CPB versus that observed in ND patients. This alteration may contribute to the vasomotor dysfunction of coronary microcirculation seen early after CP/CPB in patients with diabetes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: We investigated the changes in adherens junction proteins, such as vascular endothelial-cadherin and β-catenin, of skeletal muscle and vessels in patients with or without diabetes in the setting of cardiopulmonary bypass and cardiac operation., Methods: Skeletal muscle tissue samples were harvested pre- and post-cardiopulmonary bypass from nondiabetic (hemoglobin A1c: 5.4 ± 0.1), controlled diabetic (hemoglobin A1c: 6.3 ± 0.1), and uncontrolled diabetic patients (hemoglobin A1c: 9.6 ± 0.3) undergoing coronary artery bypass grafting operation (n = 8 per group). The expression/phosphorylation of adherens junction proteins vascular endothelial-cadherin and β-catenin were assessed by immunoblotting and immuno-histochemistry. Endothelial function of skeletal muscle arterioles was determined by videomicroscopy in response to the vasodilator substance P., Results: The protein expression of total vascular endothelial-cadherin was not changed at baseline or between pre-and post-cardiopulmonary bypass among groups. The pre-cardiopulmonary bypass level of phospho-vascular endothelial-cadherin was found to be significantly increased in the uncontrolled diabetic patients group compared with the nondiabetic or controlled diabetic groups (P < .05). The post-cardiopulmonary bypass levels of phospho-vascular endothelial-cadherin were significantly increased compared with pre-cardiopulmonary bypass in all groups (P < .05 each), and this increase was greater in the uncontrolled diabetic patients group than that of the nondiabetic or controlled diabetic groups (P < .05). Expression of basal β-catenin protein in the uncontrolled diabetic group was decreased compared with nondiabetic or controlled diabetic groups (P < .05). There were significant decreases in the β-catenin protein expression between pre- and post-cardiopulmonary bypass in all 3 groups (P < .05 each), and this decrease was greater in the uncontrolled diabetic patients group than the nondiabetic group (P < .05). There were decreases in the relaxation response of skeletal muscle arterioles to substance P after cardiopulmonary bypass in all 3 groups (P < .05), and this alteration was more pronounced in the uncontrolled diabetic patients (P < .05)., Conclusion: Uncontrolled diabetes causes inactivation and reduction in the expression of endothelial adherens junction proteins in the arterioles of skeletal muscle early after cardiopulmonary bypass. The enhanced phosphorylation of vascular endothelial-cadherin and degradation of β-catenin indicate deterioration of these proteins and damage of the cell-cell endothelial junctions, specifically in the diabetic peripheral vessels. These alterations may contribute to the increases in peripheral vascular permeability and endothelial dysfunction., Competing Interests: Confliction of interest None declared, (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: We tested the short-term effects of completely nonpulsatile versus pulsatile circulation after ventricular excision and replacement with total implantable pumps in an animal model on peripheral vascular permeability., Methods: Ten calves underwent cardiac replacement with two HeartMate III continuous-flow rotary pumps. In five calves, the pump speed was rapidly modulated to impart a low-frequency pulse pressure in the physiologic range (10-25 mm Hg) at a rate of 40 pulses per minute (PP). The remaining five calves were supported with a pulseless systemic circulation and no modulation of pump speed (NP). Skeletal muscle biopsies were obtained before cardiac replacement (baseline) and on postoperative days (PODs) 1, 7, and 14. Skeletal muscle-tissue water content was measured, and morphologic alterations of skeletal muscle were assessed. VE-cadherin, phospho-VE-cadherin, and CD31 were analyzed by immunohistochemistry., Results: There were no significant changes in tissue water content and skeletal muscle morphology within group or between groups at baseline, PODs 1, 7, and 14, respectively. There were no significant alterations in the expression and/or distribution of VE-cadherin, phospho-VE-cadherin, and CD31 in skeletal muscle vasculature at baseline, PODs 1, 7, and 14 within each group or between the two groups, respectively. Although continuous-flow total artificial heart (CFTAH) with or without a pulse pressure caused slight increase in tissue water content and histologic damage scores at PODs 7 and 14, it failed to reach statistical significance., Conclusions: There was no significant adherens-junction protein degradation and phosphorylation in calf skeletal muscle microvasculature after CFTAH implantation, suggesting that short term of CFTAH with or without pulse pressure did not cause peripheral endothelial injury and did not increase the peripheral microvascular permeability., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Cyclooxygenase-2 inhibitors have been implicated in adverse cardiac events. We hypothesize that hypercholesterolemia and ischemia may alter the myocardial response to the cyclooxygenase-2 inhibitor celecoxib., Methods: Yorkshire swine fed normal chow (CX, n = 6) or high-cholesterol diet (HCX, n = 6) underwent placement of an Ameroid constrictor on the left circumflex artery and were started on celecoxib (200 mg/day). After 7 weeks, ischemic and nonischemic myocardium was analyzed for thrombogenic ratio (thromboxane content divided by prostacyclin content), total protein oxidative stress, and expression of prostacyclin synthase, thromboxane synthase, myeloperoxidase, and superoxide dismutase. Cardiac function, tissue perfusion, and vessel density were measured., Results: HCX animals were significantly hypercholesterolemic compared with CX animals. Thrombogenic ratio was significantly higher in the HCX group than in the CX group, but prostacyclin and thromboxane synthase expression was similar in all tissues. Myocardial perfusion was decreased in the HCX group compared with the CX group. Total oxidative stress, myeloperoxidase, and superoxide dismutase were increased in ischemic tissue compared with nonischemic tissues, but there was no diet-induced difference between groups. There was no difference in capillary or arteriolar density between groups. Left ventricular contractility was greater in the HCX group than in the CX group, but there was no significant difference in heart rate, mean arterial pressure, or left ventricular pressure., Conclusions: Hypercholesterolemic patients using celecoxib may be at higher risk for thrombotic events than those with normal cholesterol, but the relationship between dyslipidemia, ischemia, and cyclooxygenase-2 inhibition is likely much more complicated than originally thought., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)