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Background: Patients with brain metastases (BrMs) from esophageal cancer have poor prognosis, the incidence of which is expected to rise due to improved survival from the primary tumor and increased neuroimaging. We aimed to identify patient and esophageal cancer characteristics associated with shorter survival in patients with BrMs and, secondly, to compare the prognosis of patients with HER2 overexpression., Methods: We retrospectively reviewed patients with BrMs from esophageal cancer at a single institution from 2008-2021. We collected patient demographics, primary tumor and BrM characteristics, and treatment. Our primary outcome was median survival from the time of BrM., Results: The median age at primary diagnosis was 66.5 years and 86% were male. Of the 49 patients, 71% had adenocarcinoma, 20% squamous cell carcinoma and 8% other. In this group, 71% of patients presented with stage III or IV disease, including 16% with synchronous primary metastatis and BrM. The median time to BrM was 10.1 months (interquartile range 1.7-22.8) and the median survival from BrM was 8.4 months (95% CI 4.8-16.8 months). On multivariable analysis, treatment with stereotactic radiosurgery (hazard ratio [HR] = 0.19; P = 0.04), surgical resection (HR 0.24; P = 0.03), and immunotherapy (HR 0.19; P = 0.04) were associated with increased survival while Karnofsky Performance Status (KPS) ≤70 (HR = 13.2; P < 0.001) was associated with decreased survival. HER2 overexpression was found in 22% of patients, but we noted no survival difference (5.2 months HER2+ vs. 9.8 months HER2neg; P = 0.95)., Conclusions: The median survival from esophageal-to-brain metastasis was 8.4 months. Patients with a single lesion, KPS score >70, and treatment with surgical resection was correlated with improved survival. Further, HER2+ patients had distinct patient and BrM characteristics., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: To externally validate the performance of the DeepDx Prostate artificial intelligence (AI) algorithm (Deep Bio Inc., Seoul, South Korea) for Gleason grading on whole-mount prostate histopathology, considering potential variations observed when applying AI models trained on biopsy samples to radical prostatectomy (RP) specimens due to inherent differences in tissue representation and sample size., Materials and Methods: The commercially available DeepDx Prostate AI algorithm is an automated Gleason grading system that was previously trained using 1133 prostate core biopsy images and validated on 700 biopsy images from two institutions. We assessed the AI algorithm's performance, which outputs Gleason patterns (3, 4, or 5), on 500 1-mm 2 tiles created from 150 whole-mount RP specimens from a third institution. These patterns were then grouped into grade groups (GGs) for comparison with expert pathologist assessments. The reference standard was the International Society of Urological Pathology GG as established by two experienced uropathologists with a third expert to adjudicate discordant cases. We defined the main metric as the agreement with the reference standard, using Cohen's kappa., Results: The agreement between the two experienced pathologists in determining GGs at the tile level had a quadratically weighted Cohen's kappa of 0.94. The agreement between the AI algorithm and the reference standard in differentiating cancerous vs non-cancerous tissue had an unweighted Cohen's kappa of 0.91. Additionally, the AI algorithm's agreement with the reference standard in classifying tiles into GGs had a quadratically weighted Cohen's kappa of 0.89. In distinguishing cancerous vs non-cancerous tissue, the AI algorithm achieved a sensitivity of 0.997 and specificity of 0.88; in classifying GG ≥2 vs GG 1 and non-cancerous tissue, it demonstrated a sensitivity of 0.98 and specificity of 0.85., Conclusion: The DeepDx Prostate AI algorithm had excellent agreement with expert uropathologists and performance in cancer identification and grading on RP specimens, despite being trained on biopsy specimens from an entirely different patient population., (© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background and Objective: Hypogonadism and frailty may impact postoperative outcomes for men undergoing radical nephrectomy (RN). We aimed to determine the prevalence of hypogonadism in men undergoing RN and whether hypogonadism and frailty are associated with adverse postoperative outcomes., Methods: We identified men undergoing RN between 2012 and 2021 using the IBM Marketscan database. Frailty was determined using the Hospital Frailty Risk Score (HFRS). Patients were considered to have hypogonadism if diagnosed <5 years before RN. Length of stay (LOS), complications, emergency department (ED) visits, and readmissions were evaluated between men with and without hypogonadism at the time of surgery. Subgroup analysis of men with hypogonadism was performed to determine the effect of testosterone replacement therapy (TRT) on clinical outcomes., Results: Among 13 598 men who underwent RN, 972 (7.1%) had hypogonadism. Men with hypogonadism were more frail compared to men without hypogonadism (HFRS: median: 8.2, interquartile range [IQR]: 5.2-11.7 vs. median: 7.0, IQR: 4.3-10.7, p < 0.001) and had increased incidence of postoperative ileus (13.0% vs. 10.8%, p = 0.045), acute kidney injury (25.5% vs. 21.6% p = 0.005), and cardiac arrest (1.2% vs. 0.6%, p = 0.034). Hypogonadism was not associated with LOS, 90-day ED visit or readmission. However, high-risk frailty was associated with increased risk of 90-day ED visit (hazard ratio [HR]: 2.1, 95% confidence interval [95% CI]: 1.9-2.4, p < 0.001) and 90-day inpatient readmission (HR: 2.6, 95% CI: 2.2-3.1, p < 0.001), compared to low-risk frailty patients. Among men with hypogonadism, TRT was not associated with any postoperative outcomes., Conclusions: Hypogonadism and frailty should be considered in the preoperative evaluation for men undergoing RN as risk factors for adverse postoperative outcomes., (© 2024 Wiley Periodicals LLC.)

Introduction: Hypogonadism is associated with frailty, lower health-related quality of life, decreased muscle mass, and premature mortality, which may predispose patients to poor postoperative outcomes. We aimed to determine the prevalence of hypogonadism in men undergoing radical cystectomy (RC) and whether hypogonadism and frailty are associated with adverse postoperative outcomes., Materials and Methods: The IBM MarketScan database was used to identify men who underwent RC between 2012 and 2021. Frailty was determined using published Hospital Frailty Risk Score ranges. Patients were considered to have hypogonadism if diagnosed within 5 years prior to RC. Length of stay (LOS), complications, emergency department (ED) visits and inpatient readmissions were compared. Sub-group analysis of men with hypogonadism was performed to determine the effect of testosterone replacement therapy (TRT) on clinical outcomes., Results: Among 3,727 men who underwent RC, 226 (6.1%) had a diagnosis of hypogonadism. Overall, 565 (15.2%) men were low-risk frailty, 2,214 (59.4%) intermediate-risk frailty, and 948 (25.4%) were high-risk frailty, and men with hypogonadism were significantly more frail compared to men without hypogonadism (P = 0.027). There was no significant difference in LOS, complications, or rate of ED visits and inpatient readmissions between cohorts (P > 0.05). However, high-risk frailty was associated with an increased risk of 90-day ED visit (HR 1.19, 95%CI 1.00-1.41, P = 0.049) and 90-day readmission (HR 1.60, 95%CI 1.29-1.97, P < 0.001) after RC. Among men with hypogonadism, 58 (25.7%) were on TRT. There was no significant difference in frailty, LOS, complications, or 90-day ED visits or 90-day inpatient readmissions between patient with hypogonadism prescribed TRT and those without TRT., Conclusions: These findings suggest that hypogonadism and preoperative frailty may be important to evaluate prior to undergoing RC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To characterize national trends in and associated outcomes of more often than annual prostate-specific antigen (PSA) screening, which we term "prosteria.", Methods: Men in the Optum Clinformatics Data Mart with ≥2 years from first PSA test to censoring at the end of insurance or available data (January 2003 to June 2019) or following exclusionary diagnoses or procedures, such as PCa treatment, were included. PSAs within 90 days were treated as one PSA. Prosteria was defined as having ≥3 PSA testing intervals of ≤270 days., Results: A total of 9,734,077 PSAs on 2,958,923 men were included. The average inter-PSA testing interval was 1.5 years, and 4.5% of men had prosteria, which increased by 0.53% per year. Educated, wealthy, non-White patients were more likely to have prosteria. Men within the recommended screening age (ie 55-69) had lower rates of prosteria. Prosteria patients had higher average PSA values (2.5 vs 1.4 ng/mL), but lower values at PCa diagnosis. Prosteria was associated with biopsy and PCa diagnosis; however, there were comparable rates of treatment within 2 years of diagnosis., Conclusion: In this large cohort study, prosteria was common, increased over time, and was associated with demographic characteristics. Importantly, there were no clinically meaningful differences in PSA values at diagnosis or rates of early treatment, suggesting prosteria leads to both overdiagnosis and overtreatment. These results support current AUA and USPTF guidelines and can be used to counsel men seeking more frequent PSA screening., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Though Wilms tumor (WT) is one of the most common malignancies in children, there is a paucity of epidemiologic studies exploring sociodemographic disparities in treatment and survival. Here, we leveraged a national cancer registry to examine sociodemographic factors associated with receipt of adjuvant therapy, either chemotherapy or radiation, as well as overall survival among pediatric patients with WT., Materials and Methods: Within the Surveillance Epidemiology and End Results database (2000-2016), we identified 2043 patients (≤ 20 years of age) with unilateral WT. Multivariable logistic regression and Cox proportional hazard models were constructed to examine the association of sociodemographic factors with, respectively, adjuvant chemotherapy/radiotherapy and overall survival (OS)., Results: Patients in the lowest SES quintile (OR 0.56, 95% CI 0.33-0.93, p = 0.03) were less likely to receive chemotherapy as compared to those in the highest SES quintile, though this association did not persist in sensitivity analyses including only patients at least 2 years of age and patients with regional/distant disease. In addition, female patients were more likely to receive chemotherapy (OR 1.46, 95% CI 1.08-1.97, p = 0.02) than male patients. Age, race, year of diagnosis, insurance status, and tumor laterality were not associated with receipt of chemotherapy. No sociodemographic variables were associated with receipt of radiotherapy. Lastly, as compared to Non-Hispanic-White patients, Hispanic patients had worse OS (HR 1.59, 95% CI 1.08-2.35, p = 0.02); no other sociodemographic variables were associated with OS., Conclusions: This study suggests multilevel sociodemographic disparities involving ethnicity and SES in WT treatment and survival., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Inactivating mutations in mitochondrial aldehyde dehydrogenase 2 (ALDH2) are highly prevalent. The most common variant allele, ALDH2*2 , is present in 40%-50% of East Asians, and causes acetaldehyde accumulation, flushing and tachycardia after alcohol intake. The relationship between alcohol intake and ALDH2 genotype on semen parameters remains unknown., Materials and Methods: We conducted a cross-sectional study to determine the association between ALDH2 genotype, alcohol consumption and semen parameters among East Asian men. Volunteers completed a survey and submitted a semen sample for analysis. Participants were genotyped to determine ALDH2 status ( ALDH2*1/*1 , ALDH2*1/*2 , ALDH2*2/*2 ), and immunohistochemical staining was used to determine protein expression of ALDH2 in spermatozoa., Results: Of 112 men 45 (40.2%) were ALDH2*2 carriers. Among ALDH2*2 carriers, alcohol consumption was associated with significantly lower total sperm motility (median 20% [interquartile range 11%-42%] vs 43% [IQR 31%-57%], p=0.005) and progressive sperm motility (19% [IQR 11%-37%] vs 36% [IQR 25%-53%], p=0.008). Among alcohol consumers, ALDH2*2 carriers had significantly lower total sperm motility (20% [IQR 11%--42%] vs 41% [IQR 19%-57%], p=0.02), progressive sperm motility (19% [IQR 11%-37%] vs 37% [IQR 17%-50%], p=0.02) and total motile sperm count (28 million [M; IQR 9-79M] vs 71M [IQR 23-150M], p=0.05) compared to ALDH2*1/*1 individuals. Secondly, ALDH2 expression in human spermatozoa was significantly lower in ALDH2*2 carriers ( ALDH2*1/*1 vs ALDH2*1/*2 , p=0.01; ALDH2*1/*1 vs ALDH2*2/*2 , p <0.001)., Conclusions: Our findings suggest genotyping ALDH2, coupled with alcohol cessation counseling, may improve semen parameters among men.

Study Design: Retrospective cohort., Objectives: Delayed ejaculation (DE) is a distressing condition characterized by a notable delay in ejaculation or complete inability to achieve ejaculation, and there are no existing reports of DE following lumbar spine surgery. Inspired by our institutional experience, we sought to assess national rates of DE following surgery of the lumbar spine., Methods: We queried the Optum De-identified Clinformatics Database for adult men undergoing surgery of the lumbar spine between 2003 and 2017. The primary outcome was the development of DE within 2 years of surgery. Multivariable logistic regression was performed to identify factors associated with the development of DE., Results: We identified 117 918 men who underwent 162 646 lumbar spine surgeries, including anterior lumbar interbody fusion (ALIF), posterior lumbar fusion (PLF), and more. The overall incidence of DE was 0.09%, with the highest rate among ALIF surgeries at 0.13%. In multivariable analysis, the odds of developing DE did not vary between anterior/lateral lumbar interbody fusion, PLF, and other spine surgeries. A history of tobacco smoking (OR = 1.47, 95% CI 1.00-2.16, P = .05) and obesity (OR = 1.56, 95% CI 1.00-2.44, P = .05) were associated with development of DE., Conclusions: DE is a rare but distressing complication of thoracolumbar spine surgery, and patients should be queried for relevant symptoms at postoperative visits when indicated.

Background: Biliary cancers are rare, and few reported cases of brain metastases from primary biliary cancers exist, especially describing patients in the United States. This report assesses the proportion and incidence of brain metastases arising from primary biliary cancers [cholangiocarcinoma (CCA) and gallbladder cancer] at Stanford University and the University of California, San Francisco, describes clinical characteristics, and provides a case series., Methods: We queried 3 clinical databases at Stanford and the University of California, San Francisco to retrospectively identify and review the charts of 15 patients with brain metastases from primary biliary cancers occurring between 1990 to 2020., Results: Among patients with brain metastases analyzed at Stanford (3,585), 6 had a primary biliary cancer, representing 0.17% of all brain metastases. Among biliary cancer patients at the University of California, San Francisco (1,055), 9 had brain metastases, representing an incidence in biliary cancer of 0.85%. A total of 15 biliary cancer patients with brain metastases were identified at the two institutions. Thirteen out of 15 patients (86.7%, 95% CI: 59.5-98.3) were female. The median overall survival from primary biliary cancer diagnosis was 214 days (95% CI: 71.69-336.82 days) and subsequent OS from the time of brain metastasis diagnosis was 57 days (95% CI: 13.43-120.64 days). Death within 90 days of brain metastasis diagnosis occurred in 66.67% of patients (95% CI: 38.38-88.17)., Conclusions: Brain metastases from primary biliary cancers are rare, with limited survival once diagnosed. This report can aid health care providers in caring for patients with brain metastases from primary biliary cancers., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-21-818/coif). JLW reports having received payment from MJH Life Sciences for a continuing education presentation regarding treatments for IDH1 mutations in cholangiocarcinoma. RKK reports receiving grant support for the UCSF Hepatobiliary Tissue Bank and Registry from the Bili Project Foundation, Inc and The Cholangiocarcinoma Foundation. RKK reports research support paid to their institution for clinical trial conduct from: Agios, Astra Zeneca, Bayer, BMS, Eli Lilly, EMD Serono, Exelixis, Genentech/Roche, Loxo Oncology, Merck, Novartis, Partner Therapeutics, QED, Relay Therapeutics, Surface Oncology, Taiho. RKK reports consulting fees paid to their institution from: Astra Zeneca, Agios, BMS, Merck, Exelixis, Ipsen. RKK reports serving as a Co-Chair of the Scientific and Medical Advisory Board of Cholangiocarcinoma Foundation and as a Member of the Governance Board of the International Liver Cancer Association. MHG reports grants (U54CA261717 and K08NS901527) to fund research projects from The National Institute of Health. The other authors have no conflicts of interest to declare., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)

Purpose: The literature assessing outcomes of partial adrenalectomy (PA) among patients with pheochromocytoma patients is largely limited to isolated, single-institution series. We aimed to perform a population-level comparison of outcomes between patients undergoing PA versus those undergoing total adrenalectomy (TA)., Methods: The Surveillance, Epidemiology, and End Results (SEER) database (1975-2016) was queried to identify adults with pheochromocytoma who underwent either PA or TA. Survival was assessed using multivariable Cox proportional hazards regression, Fine and Gray competing-risks regression, propensity score matching, Kaplan-Meier analysis, and cumulative incidence plots., Results: 286 patients (PA: 101, TA: 185) were included in this study. As compared to those undergoing TA, patients undergoing PA had fewer tumors ≥ 8 cm in size (28.7% versus 42.7%, p = 0.048) and were more likely to have localized disease (61.4% versus 44.3%, p = 0.01). In multivariable analysis, patients undergoing PA demonstrated similar all-cause mortality (HR = 0.71, 95% CI 0.44-1.14, p = 0.16) and cancer-specific mortality (HR = 0.64, 95% CI 0.35-1.17, p = 0.15) compared to those who underwent TA. Following 1:1 propensity score matching, Kaplan-Meier analysis revealed no difference in overall survival between PA and TA groups (p = 0.26) nor was there a difference in the cumulative incidence of cancer-specific mortality (p = 0.29)., Conclusions: In this first population-level comparison of outcomes among patients with pheochromocytoma undergoing PA and those undergoing TA, we found no long-term differences in any survival metric between groups. PA circumvents the need for lifelong corticoid replacement therapy and remains a promising option for patients with bilateral or recurrent pheochromocytoma., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: International studies have demonstrated increasing rates of sexual dysfunction amidst the coronavirus disease 2019 (COVID-19) pandemic; however, the impact of the pandemic on female sexual function in the United States is unknown., Aim: To assess the impact of the COVID-19 pandemic on female sexual function and frequency in the United States., Methods: A pre-pandemic survey containing the Female Sexual Function Index (FSFI) and demographic questions was completed by adult women in the United States from October 20, 2019 and March 1, 2020. The same women were sent a follow-up survey also containing the FSFI, as well as the Patient Health Questionnaire for Depression and Anxiety with 4 items (PHQ-4), and questions pertaining to mask wearing habits, job loss, and relationship changes. Risk for female sexual dysfunction (RFSD) was defined as FSFI < 26.55., Main Outcome Measure: Differences in pre-pandemic and intra-pandemic female sexual function, measured by the FSFI, and sexual frequency., Results: Ninety-one women were included in this study. Overall FSFI significantly decreased during the pandemic (27.2 vs 28.8, P = .002), with domain-specific decreases in arousal (4.41 vs 4.86, P = .0002), lubrication (4.90 vs 5.22, P = .004), and satisfaction (4.40 vs 4.70, P = .04). There was no change in sexual frequency. Contingency table analysis of RFSD prior to and during the pandemic revealed significantly increased RFSD during the pandemic (P = .002). Women who developed RFSD during the pandemic had higher PHQ-4 anxiety subscale scores (3.74 vs 2.53, P = .01) and depression subscale scores (2.74 vs 1.43, P = .001) than those who did not. Development of FSD was not associated with age, home region, relationship status, mask wearing habits, knowing someone who tested positive for COVID-19, relationship change, or job loss and/or reduction during the pandemic., Conclusion: In this population of female cannabis users, risk for sexual dysfunction increased amidst the COVID-19 pandemic and is associated with depression and anxiety symptoms. Bhambhvani HP, Chen T, Wilson-King AM, et al. Female Sexual Function During the COVID-19 Pandemic in the United States. Sex Med 2021;9:100355., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Following passage of the Affordable Care Act, Medicaid access was expanded in several states beginning in 2014. We sought to determine the oncologic implications by comparing outcomes between testicular germ cell tumor patients with Medicaid and those without insurance, and by assessing for changes in outcomes after 2014., Methods: A total of 18,506 men with seminomatous or nonseminomatous germ cell tumors were identified within the Surveillance, Epidemiology, and End Results database (2007-2016). Multivariable Cox proportional hazards, Fine and Gray competing-risks regression, propensity score matching, cumulative incidence plots and segmented Poisson regression models were used., Results: Compared to no insurance, Medicaid insurance was not associated with differences in all-cause mortality or cancer-specific mortality among seminoma patients (all-cause mortality: HR=1.24, p=0.87; cancer-specific mortality: HR=0.92, p=0.75) or nonseminoma patients (all-cause mortality: HR=1.13, p=0.33; cancer-specific mortality: HR=1.10, p=0.51). Among matched Medicaid and uninsured patients, there was again no difference in cancer-specific mortality for those with seminoma (p=0.81) or nonseminoma (p=0.23). There was a 99% increase in Medicaid enrollment in expansion states in the post-Affordable Care Act era. There was no difference in post-expansion all-cause mortality between expansion states and nonexpansion states for men with seminoma (p=0.42) or nonseminoma (p=0.53)., Conclusions: Medicaid enrollment increased in expansion states following the Affordable Care Act. However, there was no difference in survival between Medicaid patients and uninsured patients, or between patients in expansion states versus nonexpansion states, highlighting the need for population-level policy interventions to improve access and quality of care among testicular cancer patients with Medicaid.

Objective: Although past studies have associated external-beam radiation therapy (EBRT) with higher incidences of secondary neoplasms (SNs), its effect on SN development from pediatric low-grade gliomas (LGGs), defined as WHO grade I and II gliomas of astrocytic or oligodendrocytic origin, is not well understood. Utilizing a national cancer registry, the authors sought to characterize the risk of SN development after EBRT treatment of pediatric LGG., Methods: A total of 1245 pediatric patient (aged 0-17 years) records from 1973 to 2015 were assembled from the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable subdistribution hazard regression models were used to evaluate the prognostic impact of demographic, tumor, and treatment-related covariates. Propensity score matching was used to balance baseline characteristics. Cumulative incidence analyses measured the time to, and rate of, SN development, stratified by receipt of EBRT and controlled for competing mortality risk. The Fine and Gray semiparametric model was used to estimate future SN risk in EBRT- and non-EBRT-treated pediatric patients., Results: In this study, 366 patients received EBRT and 879 did not. Forty-six patients developed SNs after an LGG diagnosis, and 27 of these patients received EBRT (OR 3.61, 95% CI 1.90-6.95; p < 0.001). For patients alive 30 years from the initial LGG diagnosis, the absolute risk of SN development in the EBRT-treated cohort was 12.61% (95% CI 8.31-13.00) compared with 4.99% (95% CI 4.38-12.23) in the non-EBRT-treated cohort (p = 0.013). Cumulative incidence curves that were adjusted for competing events still demonstrated higher rates of SN development in the EBRT-treated patients with LGGs. After matching across available covariates and again adjusting for the competing risk of mortality, a clear association between EBRT and SN development remained (subhazard ratio 2.26, 95% CI 1.21-4.20; p = 0.010)., Conclusions: Radiation therapy was associated with an increased risk of future SNs for pediatric patients surviving LGGs. These data suggest that the long-term implications of EBRT should be considered when making treatment decisions for this patient population.

Introduction: Reduction of opioids is an important goal in the care of patients undergoing radical cystectomy (RC). Liposomal bupivacaine (LB) has been shown to be a safe and effective pain reliever in the immediate postoperative period and has been reported to reduce postoperative opioid requirements. Since the liposomal formulation is predicated on slow systemic absorption, the amount of bupivacaine administered is notably higher than that typically used with standard bupivacaine (SB) formulations. In addition, LB is costly, not universally available, and studies comparing this formulation to SB are lacking. We sought to determine if there is a difference in postoperative opioid requirements in patients who receive LB vs. high dose SB at the time of RC., Methods: In May 2019 we transitioned to administration of high-volume SB injected intraoperatively at the time of RC. This prospective cohort was compared to a historical cohort of patients who received injection of LB at the time of surgery. Primary endpoints included postsurgical opioid use measured in morphine equivalent dose (MED) and patient-reported Numeric Rating Scale (NRS) pain scores and length of stay. All patients were managed using principles of enhanced recovery after surgery (ERAS)., Results: From May 2019 through August 2019, 28 patients underwent RC and met eligibility criteria to receive SB at the time of surgery. They were compared to a historical cohort of 34 patients who received LB between November 2017 and July 2018. There was no difference in MED exposure either in the postanesthesia care unit (SB 9.0 ± 8.9 MED vs. LB 6.5 ± 9.4 MED, P= 0.29) or during the remainder of the hospital stay (SB 36.8 ± 56.9 MED vs. LB 42.1 ± 102.5 MED, P= 0.81), no difference in NRS pain scores on postoperative day 1 (SB 2.6 ± 1.6 vs. LB 2.1 ± 1.7, P= 0.23), day 2 (SB 2.4 ± 1.8 vs. LB 1.9 ± 1.6, P= 0.19), or day 3 (SB 1.9 ± 1.8 vs. LB 1.7 ± 1.7, P= 0.69) and no difference in length of stay (SB 5.0 ± 1.7 days, LB 4.9 ± 3.3 days, P= 0.93). Subgroup analysis of open RC and robotic-assisted RC showed no significant difference in MED or pain scores between LB and SB patients., Conclusions: Among patients undergoing RC under ERAS protocol there was no significant difference in postoperative opioid consumption, NRS pain scores, or length of stay among patients receiving SB compared to LB., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: International studies have suggested that social disruptions caused by the COVID-19 pandemic have led to sexual dysfunction, but the impact on males in the United States is less defined., Aim: To examine changes in male sexual function during the COVID-19 pandemic and to evaluate associated demographic variables., Methods: Prepandemic survey data was collected between October 20, 2019 and March 1, 2020 on adult males in the United States. Follow-up survey data collected for comparison during the COVID-19 pandemic between August 1, 2020 and October 10, 2020 included International Index of Erectile Function (IIEF) scores, Patient Health Questionnaire for Depression and Anxiety with 4 items (PHQ-4) scores, and questions regarding sexual frequency. Questions were also asked about mask-wearing habits, job loss, relationship changes, and proximity to individuals who tested positive for COVID-19., Main Outcome Measures: Differences in prepandemic and pandemic male sexual function assessed by self-reported IIEF domain scores and sexual frequency RESULTS: Seventy six men completed both prepandemic and pandemic surveys with a mean age of 48.3 years. Overall, there were no differences in either overall IIEF score or any subdomain score when comparing men's pre-pandemic and pandemic survey data. There was an increase in sexual frequency during the pandemic with 45% of men reporting sex ten or more times per month during the pandemic compared to only 25% of men prior to the pandemic (P = .03). Among the subgroup of 36 men who reported a decrease in IIEF, the decrease was an average of 3.97, and significantly associated with higher PHQ-4 depression subscale scores (1.78 vs 1.03, P = .02)., Conclusion: The COVID-19 pandemic is associated with increased sexual frequency and no change in overall sexual function in males in the United States. Interventions intended to promote male sexual health during the COVID-19 pandemic should include a focus on mental health. Chen T, Bhambhvani HP, Kasman AM, et al. The Association of the COVID-19 Pandemic on Male Sexual Function in the United States: A Survey Study of Male Cannabis Users. J Sex Med 2021;9:100340., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Previous reports of deep learning-assisted assessment of Mayo endoscopic subscore (MES) in ulcerative colitis have only explored the ability to distinguish disease remission (MES 0/1) from severe disease (MES 2/3) or inactive disease (MES 0) from active disease (MES 1-3). We sought to explore the utility of deep learning models in the automated grading of each individual MES in ulcerative colitis., Methods: In this retrospective study, a total of 777 representative still images of endoscopies from 777 patients with clinically active ulcerative colitis were graded using the MES by two physicians. Each image was assigned an MES of 1, 2, or 3. A 101-layer convolutional neural network model was trained and validated on 90% of the data, while 10% was left for a holdout test set. Model discrimination was assessed by calculating the area under the curve (AUC) of a receiver operating characteristic as well as standard measures of accuracy, specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV)., Results: In the holdout test set, the final model classified MES 3 disease with an AUC of 0.96, MES 2 disease with an AUC of 0.86, and MES 1 disease with an AUC 0.89. Overall accuracy was 77.2%. Across MES 1, 2, and 3, average specificity was 85.7%, average sensitivity was 72.4%, average PPV was 77.7%, and the average NPV was 87.0%., Conclusion: We have demonstrated a deep learning model was able to robustly classify individual grades of endoscopic disease severity among patients with ulcerative colitis., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Male factor infertility (MFI) is a common medical condition which requires high-quality research to guide clinical practice; however, systematic reviews (SRs) and meta-analyses (MAs) often vary in quality, raising concerns regarding the validity of their results. We sought to perform an objective analysis of SRs and MAs in MFI treatment and management and to report on the quality of published literature., Methods: A comprehensive search in PubMed/MEDLINE and Embase was used to identify relevant publications. Primary search terms were male infertility, male sterility, and male subfertility. Two authors independently performed searches, screened citations for eligibility, extracted data for analysis, and graded methodological quality using the validated AMSTAR (A Measurement Tool to Assess Systematic Reviews) instrument, a validated tool used in the critical appraisal of SRs/MAs., Results: Of 27 publications met inclusion criteria and were included in the analysis. Mean AMSTAR score (± SD) among all publications was 7.4 (1.9) out of 11, reflecting "fair to good" quality. Non-pharmacological medical treatment for MFI was the most commonly assessed intervention (n = 13, 48.1%). No publications met all AMSTAR criteria. While the number of SRs/MAs has increased over time (P = 0.037), the quality of publications has not significantly changed (P = 0.72). SRs/MAs of the Cochrane Library had higher AMSTAR score than non-Cochrane SRs/MAs (8.5 vs 6.3, P = 0.002)., Conclusions: The methodological quality of SRs/MAs should be assessed to ensure high-quality evidence for clinical practice guidelines in MFI treatment and management. This review highlights a need for increased effort to publish high-quality studies in MFI treatment and management., (© 2021 American Society of Andrology and European Academy of Andrology.)

Introduction and Objective: Ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL) are standard treatments for intermediate-size (15-20 mm) kidney stones but differ in their postoperative recovery, stone-free rates, and complication risks. We aimed to evaluate what affects patient treatment preferences. Methods: Patients with urinary stone disease completed a choice-based conjoint analysis exercise assessing four treatment attributes associated with URS and PCNL. A sensitivity analysis using a market simulator was performed, and the relative importance of each attribute was calculated. Differences in treatment preferences by demographic subgroup were assessed. Results: A total of 58 patients completed the conjoint analysis exercise. Stone-free rate was the most important treatment attribute, while the length of hospital stay and cosmesis were less important. Overall, sensitivity analysis based on market simulation scenarios predicted an almost equal preference for URS (52.4%) compared with PCNL (47.6%) for treatment of an intermediate-size stone. Older patients (>65 years old) expressed their stronger preferences for lower infection rates and shorter hospital stays, and were more likely to prefer URS (67.2%, 95% confidence interval [CI]: 52% to 82.5%) compared with younger patients (20-34 years old) (20.3%, 95% CI: 0% to 41.5%) who preferred higher procedure success rates and fewer repeat procedures. Conclusion: Conjoint analysis predicts nearly equal patient preference for URS or PCNL for the treatment of intermediate-size kidney stones. Older patients prefer the lower urinary tract infection risk and shorter hospital stay associated with URS, while younger patients prefer higher stone-free rates associated with PCNL. These results can help guide urologists in counseling patients and improve the shared decision-making process.

Background: Though testicular cancer is the most common cancer in young men, there is a paucity of epidemiologic studies examining sociodemographic disparities in adjuvant therapy and outcomes. We examined the associations of sociodemographic factors with retroperitoneal lymph node dissection (RPLND) and survival among patients with nonseminomatous germ cell tumors (NSGCTs)., Methods: Within the Surveillance Epidemiology and End Results database (2005-2015), we identified 8,573 patients with nonseminomatous germ cell tumors. Multivariable logistic regression and Fine-Gray competing-risks regression models were constructed to examine the association of sociodemographic factors (neighborhood SES (nSES), race, and insurance) with, respectively, adjuvant RPLND within 1 year of diagnosis and cancer-specific mortality., Results: Patients in the lowest nSES quintile (OR 0.59, 95% CI = 0.40-0.88, P = 0.01) and Black patients (OR 0.41, 95% CI = 0.15-1.00, P= 0.058) with stage II disease were less likely to receive RPLND compared to those in the highest quintile and White patients, respectively. Stage III patients with Medicaid (OR 0.64, 95% CI = 0.46-0.89, P= 0.009) or without insurance (OR 0.46, 95% CI = 0.27-0.76, P= 0.003) were less likely to receive RPLND compared to patients with private insurance. Lowest quintile nSES patients of all disease stages and Black patients with stage I disease (HR = 2.64, 95% CI = 1.12-6.20, P = 0.026) or stage II disease (HR=4.93, 95% CI = 1.48-16.44, P = 0.009) had higher risks of cancer-specific mortality compared to highest quintile nSES and White patients, respectively., Conclusions: This national study found multilevel, stage-specific sociodemographic disparities in receipt of RPLND and survival., Competing Interests: Conflict of interest The authors declare no potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: When exploring survival outcomes for patients with bladder cancer, most studies rely on conventional statistical methods such as proportional hazards models. Given the successful application of machine learning to handle big data in many disciplines outside of medicine, we sought to determine if machine learning could be used to improve our ability to predict survival in bladder cancer patients. We compare the performance of artificial neural networks (ANN), a type of machine learning algorithm, with that of multivariable Cox proportional hazards (CPH) models in the prediction of 5-year disease-specific survival (DSS) and overall survival (OS) in patients with bladder cancer., Subjects and Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 18 program database was queried to identify adult patients with bladder cancer diagnosed between 1995 and 2010, yielding 161,227 patients who met our inclusion criteria. ANNs were trained and tested on an 80/20 split of the dataset. Multivariable CPH models were developed in parallel. Variables used for prediction included age, sex, race, grade, SEER stage, tumor size, lymph node involvement, degree of extension, and surgery received. The primary outcomes were 5-year DSS and 5-year OS. Receiver operating characteristic curve analysis was conducted, and ANN models were tested for calibration., Results: The area under the curve for the ANN models was 0.81 for the OS model and 0.80 for the DSS model. Area under the curve for the CPH models was 0.70 for OS and 0.81 for DSS. The ANN OS model achieved a calibration slope of 1.03 and a calibration intercept of -0.04, while the ANN DSS model achieved a calibration slope of 0.99 and a calibration intercept of -0.04., Conclusions: Machine learning algorithms can improve our ability to predict bladder cancer prognosis. Compared to CPH models, ANNs predicted OS more accurately and DSS with similar accuracy. Given the inherent limitations of administrative datasets, machine learning may allow for optimal interpretation of the complex data they contain., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Brain metastases from endometrial cancer are rare and poorly described. We aimed to estimate the proportion of brain metastases at our institution that arose from endometrial cancer, and to detail clinicopathologic features and survival outcomes., Methods: We retrospectively identified and reviewed the charts of 30 patients with brain metastases from endometrial cancer seen at Stanford Hospital from 2008 to 2018., Results: Among all patients with brain metastases, the proportion arising from endometrial cancer was 0.84%. The median age at diagnosis was 62 years (range, 39-79 years), and the median overall survival from brain metastasis diagnosis was 6.8 months (range, 1.0-58.2 months). Most patients harbored endometrioid histology (53.3%), and some had concurrent metastases to lung (50.0%), bone (36.7%), and liver (20.0%). The median time from endometrial cancer diagnosis to brain metastasis development was 20.8 months (range, 1.4 months to 11.2 years), and the median number of brain metastases was 2 (range, 1-20). Patients with non-endometrioid histologies had more brain metastases than those with endometrioid histology (6.21 vs. 2.44, P = 0.029). There was no difference in overall survival by histology., Conclusions: We describe the largest cohort to date of patients with brain metastases originating from endometrial cancer. These patients represent a small fraction of all patients with brain metastases and have poor prognoses. These data enable providers caring for patients with brain metastases from endometrial cancer to appropriately counsel their patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Genitourinary rhabdomyosarcoma (GU-RMS) is a rare, pediatric malignancy originating from embryonic mesenchyme. Current approaches to prognostication rely upon conventional statistical methods such as Cox proportional hazards (CPH) models and have suboptimal predictive ability. Given the success of deep learning approaches in other specialties, we sought to develop and compare deep learning models with CPH models for the prediction of 5-year survival in pediatric GU-RMS patients., Methods: Patients less than 20 years of age with GU-RMS were identified within the Surveillance, Epidemiology, and End Results (SEER) database (1998-2011). Deep neural networks (DNN) were trained and tested on an 80/20 split of the dataset in a 5-fold cross-validated fashion. Multivariable CPH models were developed in parallel. The primary outcomes were 5-year overall survival (OS) and disease-specific survival (DSS). Variables used for prediction were age, sex, race, primary site, histology, degree of tumor extension, tumor size, receipt of surgery, and receipt of radiation. Receiver operating characteristic curve analysis was conducted, and DNN models were tested for calibration., Results: 277 patients were included. The area under the curve (AUC) for the DNN models was 0.93 for OS and 0.91 for DSS. AUC for the CPH models was 0.82 for OS and 0.84 for DSS. The DNN models were well-calibrated: OS model (slope = 1.02, intercept = -0.06) and DSS model (slope = 0.79, intercept = 0.21)., Conclusions: A deep learning-based model demonstrated excellent performance, superior to that of CPH models, in the prediction of pediatric GU-RMS survival. Deep learning approaches may enable improved prognostication for patients with rare cancers., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To describe clinical characteristics and identify prognostic factors among men with testicular sarcoma, and to compare survival with other testicular cancers., Methods: The surveillance, epidemiology, and end results (SEER) database (1975-2016) was queried to identify adults with testicular sarcoma. Multivariable Cox proportional hazards, Fine and Gray competing-risks regression, propensity score matching, and Kaplan-Meier analyses were used., Results: 230 men were included in this study. Median age at diagnosis was 58 years (range 18-94), and median OS was 10.3 years. Patients with tumors larger than 8 cm in size had worse OS (HR 1.88, p = 0.016) compared to patients with tumors < 8 cm. Disease with distant metastasis was associated with worse OS (HR 4.70, p < 0.0001) and worse CSS (HR 11.41, p < 0.0001) as compared to disease localized to the testis. Men with rhabdomyosarcoma had worse CSS (HR 3.25, p = 0.03) as compared to men with liposarcoma. Testicular sarcoma patients had worse OS than matched patients with either seminomatous germ cell tumors (GCTs, p < 0.0001) or nonseminomatous GCTs (p = 0.0019), and similar survival to matched patients with sex cord stromal tumors, testicular lymphoma, or sarcomas of the lower limb-the most common anatomic site of origin of soft tissue sarcomas., Conclusions: In the largest cohort of men with testicular sarcoma to date, we identified tumor size, disease extent, and rhabdomyosarcoma histology as independent predictors of worse survival. Stage-adjusted survival was worse as compared to men with GCTs, and similar to men with sex cord stromal tumors, testicular lymphoma, and sarcomas of other primary sites.

INTRODUCTION We sought to describe clinical characteristics and identify prognostic factors among patients with primary malignancies of the epididymis (PMEs)., Materials and Methods: The Surveillance, Epidemiology, and End Results (SEER) database (1975-2015) was queried to identify patients with PME. Descriptive statistics and multivariable Cox proportional hazards models were used., Results: Eighty-nine patients with PME were identified. Median age was 57 years (5-85), and median overall survival (OS) was 16.8 years. The most commonly represented histologies were rhabdomyosarcoma (19.1%), B-cell lymphoma (16.9%), leiomyosarcoma (16.9%), and liposarcoma (12.4%). In multivariable analysis, tumor size ≥ 4 cm was associated with worse OS (HR = 4.46, p = 0.01) compared to tumors < 4 cm. Patients with nonsarcomatoid histology had OS similar to patients with sarcomatoid histology (HR = 0.95, p = 0.92). Disease with regional invasion (HR = 5.19, p = 0.007) and distant metastasis (HR = 29.80, p = 0.0002) had worse OS compared to localized disease. Receipt of radiotherapy was associated with enhanced OS (HR = 0.10, p = 0.006), whereas receipt of chemotherapy was not associated with OS., Conclusions: We describe the largest cohort of PMEs to date. Larger lesions and tumor stage were independently associated with poor overall survival, while receipt of radiotherapy was associated with enhanced overall survival.

Background: Nonsquamous penile cancers comprise 5% of penile malignancies, though their clinicopathologic features and prognostic significance remain unknown. We used a national cancer registry to detail clinical characteristics and compare cancer-specific mortality (CSM) of nonsquamous cancers with squamous cell carcinoma (SCC)., Methods: The Surveillance, Epidemiology, and End Results (SEER) database (1975-2016) was queried to identify adults with nonsquamous penile cancer and penile SCC. Multivariable Fine and Gray competing-risks regression, propensity score matching, and cumulative incidence plots were used., Results: 666 men with nonsquamous penile cancer and 5,894 men with penile SCC were identified. The most commonly represented nonsquamous histological subtypes were Kaposi sarcoma (n = 183, 27.5%), melanoma (n = 74, 11.1%), basal cell carcinoma (n = 65, 9.8%), and extramammary Paget disease (n = 42, 6.3%). Cumulative incidence plots revealed a 10-year CSM rate of 32.6% in the nonsquamous penile cancer group and 25.6% in the matched penile SCC group (P < 0.0001). Among Kaposi sarcoma patients and matched SCC patients, we found a 10-year CSM rate of 29.6% in the Kaposi sarcoma group and 15.3% in the penile SCC group (P = 0.002). Similarly, a comparison of penile melanoma patients with matched SCC patients revealed a 10-year CSM rate of 38.4% in the melanoma group and 16.6% in the SCC group (P = 0.002). There was no difference in CSM between patients with basal cell carcinoma and SCC. In a sensitivity analysis limiting year of diagnosis to 2000 and onward, we found no difference in CSM between the general nonsquamous cohort or the Kaposi sarcoma cohort and matched SCC patients, but contemporary melanoma patients maintained worse CSM with a 10-year rate of 38.4% vs. 15.8% in matched SCC patients (P = 0.045)., Conclusions: The most common nonsquamous penile cancers are Kaposi sarcoma, melanoma, and basal cell carcinoma. Overall, CSM is higher in nonsquamous penile cancers as compared to stage-matched SCC. Outcomes are similar in modern patients, likely due to improved control of systemic HIV in patients with Kaposi sarcoma. However, men with penile melanoma continue to experience a higher rate of CSM., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Immunotherapy for patients with melanoma with brain metastasis has significantly improved outcomes; however, it has also been characterized by potentially dangerous immune-related adverse events (IRAEs). Several reports have suggested that these reactions can precede improved treatment responses. For intracranial disease control, we sought to identify if such an association exists., Methods: We conducted a retrospective chart review of patients with melanoma who underwent immunotherapy treatment after diagnosis of brain metastasis. The study cohort was then stratified into 2 groups based on their history of developing an IRAE that prompted discontinuation of that regimen. The primary outcome variable included intracranial progression-free survival (PFS). Kaplan-Meier and Cox proportional hazard analyses were used to evaluate survival and predictors of outcomes., Results: Fifty-two patients met the inclusion criteria, 17 of whom experienced severe IRAEs that led to discontinuation of immunotherapy. Median intracranial PFS was 19.9 versus 10.5 months (P = 0.053) in patients who did and did not experience severe IRAEs prompting discontinuation, respectively. No additional outcome benefits were identified for systemic PFS or overall survival (mean, 33.1 months and 27.6 months, respectively). Multivariable analysis identified BRAF mutation status as a negative prognosticator of brain progression (P = 0.013; hazard ratio, 3.90). Initial treatment with BRAF inhibitor was also a negative predictor of all-cause mortality (P = 0.015; hazard ratio, 10.73)., Conclusions: Immune-related adverse events may signify an underlying immunogenic response that has intracranial disease control benefits. Despite their associated side effects, immunotherapies continue to show promising outcomes as a first-line agent for melanoma with brain metastasis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Cannabis use has increased in the last decade, and the impact of cannabis on female sexual function remains unclear., Aim: To assess the impact of frequency of use, chemovar (tetrahydrocannabinol, cannabinol, or both) type, and method of consumption on female sexual function among cannabis users., Methods: Adults who visited a single-partner cannabis dispensary's locations were invited to participate in an uncompensated, anonymous online survey October 20, 2019 and March 12, 2020. The survey assessed baseline demographics, health status, cannabis use habits as well as used the validated Female Sexual Function Index (FSFI) to assess sexual function., Main Outcome Measure: The main outcomes of this study are the total FSFI score (sexual dysfunction cutoff <26.55) and subdomain scores including desire, arousal, lubrication, orgasm, satisfaction, and pain., Results: A total of 452 women responded with the majority between the ages of 30-49 years (54.7%) and in a relationship or married (81.6%). Of them,72.8% reported using cannabis more than 6 times per week, usually through smoking flower (46.7%). Women who reported more cannabis use, reported higher FSFI scores (29.0 vs 26.7 for lowest vs highest frequencies of reported use, P = .003). Moreover, an increase in cannabis use frequency by one additional use per week was associated with an increase in total FSFI (β = 0.61, P = .0004) and subdomains including desire domain (P = .02), arousal domain (P = .0002), orgasm domain (P = .002), and satisfaction domain (P = .003). For each additional step of cannabis use intensity (ie, times per week), the odds of reporting female sexual dysfunction declined by 21% (odds ratio: 0.79, 95% confidence interval: 0.68-0.92, P = .002). Method of consumption of cannabis and chemovar type did not consistently impact FSFI scores or odds of sexual dysfunction., Conclusion: Increased frequency of marijuana use is associated with improved sexual function among female users, whereas chemovar type, method of consumption, and reason for use does not impact outcomes. Kasman AM, Bhambhvani HP, Wilson-King G, et al. Assessment of the Association of Cannabis on Female Sexual Function With the Female Sexual Function Index. Sex Med 2020;8:699-708., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate, with pre-COVID-19 data, whether parental exposure to severe systemic infections near the time of conception is associated with pregnancy outcomes., Design: Retrospective cohort study., Setting: Population-based study covering births within the United States from 2009 to 2016., Participants: The IBM MarketScan Research database covers reimbursed health care claims data on inpatient and outpatient encounters that are privately insured through employment-sponsored health insurance. Our analytic sample included pregnancies to paired fathers and mothers., Interventions(s): Parental preconception exposure (0-6 months before conception) to severe systemic infection (e.g., sepsis, hypotension, respiratory failure, critical care evaluation)., Main Outcome Measure(s): Preterm birth (i.e., live birth before 37 weeks) and pregnancy loss., Result(s): A total of 999,866 pregnancies were recorded with 214,057 pregnancy losses (21.4%) and 51,759 preterm births (5.2%). Mothers receiving intensive care in the preconception period had increased risk of pregnancy loss, as did fathers. Mothers with preconception sepsis had higher risk of preterm birth and pregnancy loss, and paternal sepsis exposure was associated with an increased risk of pregnancy loss. Similar results were noted for hypotension. In addition, a dose response was observed for both mothers and fathers between preconception time in intensive care and the risk of preterm birth and pregnancy loss., Conclusion(s): In a pre-COVID-19 cohort, parental preconception severe systemic infection was associated with increased odds of preterm birth and pregnancy loss when conception was soon after the illness., (Copyright © 2020. Published by Elsevier Inc.)

Introduction: We sought to characterize public interest in elective urological procedures amid the COVID-19 pandemic, and specifically after the Centers for Medicare and Medicaid Services and the American Urological Association recommended cessation of all nonessential procedures., Methods: We extracted relative search volumes from Google Trends™ (January 2015 to May 2020) for keywords related to the 4 procedure categories of male infertility, erectile dysfunction, Peyronie's disease and vasectomy. The most popular keywords in each category were used to assess immediate (30 days preceding and following official recommendation from Centers for Medicare and Medicaid Services on March 18, 2020) and long-term (January 1, 2015 to March 18, 2020 vs March 19, 2020 to May 21, 2020) shifts in public interest. Lastly, we assessed geographical variations in public interest during the phase I reopening period from April 24 to May 31, 2020., Results: There was an immediate reduction in interest across all 4 categories following the Centers for Medicare and Medicaid Services recommendation. Long-term post-announcement relative search volume was lower than pre-announcement relative search volume in all categories as well, namely male infertility (54.33% vs 68.74%, p=0.02), erectile dysfunction (45.00% vs 76.74%, p <0.0001), Peyronie's disease (48.33% vs 77.95%, p <0.0001) and vasectomy (51.33% vs 66.73%, p=0.0005). During the phase I reopening period the relative search volume for vasectomy was higher in states that reopened early than in states that reopened late (60.29% vs 50.52%, p=0.029)., Conclusions: Public interest in elective urological procedures decreased following the onset of the COVID-19 pandemic and recommendations from the Centers for Medicare and Medicaid Services. Interest rebounded in May, seemingly driven by states that lifted their stay-at-home order earlier than others.

We determined how often patients with epilepsy presented to the emergency department (ED) for seizure and the frequency and predictors for undergoing emergent neuroimaging during those visits. We conducted a retrospective population-based cohort study using administrative claims' data from 2007 to 2015. Adults with epilepsy were identified based on a diagnosis of epilepsy and an outpatient prescription for an antiepileptic medication. The Bonferroni corrected significance level was 0.0018. We identified 381,362 patients with a mean follow-up period of 1.99 years, of whom 35,015 (9.2%) patients presented to the ED for seizure at least once. Patients with at least one ED visit were younger, more likely to be male, had fewer comorbidities, and had longer follow-up as compared with those with no ED visit (all p < 0.001). Among the 35,015 patients presenting to the ED, 13.6% had neuroimaging, mostly commonly head computed tomography (CT; 95.5%). Patients undergoing neuroimaging were younger (46 versus 48 years) and with higher rates of psychosis (17.4% versus 13.8%) and depression (16.1% versus 12.2%; p < 0.001). This helps to quantify the burden of ED and emergent neuroimaging utilization for patients with epilepsy and can help inform efforts to curtail unnecessary neuroimaging., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

While the majority of brain metastases arise from lung cancer, breast cancer, or melanoma, new treatments and improved prognoses have altered the profile of primary cancers that metastasize to the brain. We sought to determine the proportion of brain metastases from less common primary sites and conduct trend analyses. We reviewed the charts of 3585 patients with brain metastases seen at our institution from 2008 to 2018. We determined the primary site for each of these patients, and the Mann-Kendall test was used to evaluate temporal trends in the yearly proportion of brain metastases originating from each primary cancer. The five most common primary sites were lung (43.0%), breast (19.9%), melanoma (8.2%), renal (5.0%), and colorectal (3.8%). The proportion of yearly brain metastases originating from breast cancer (p = 0.029) and melanoma (p = 0.013) decreased by 23.8% and 46.7%, respectively, from 2008 (0.21 breast, 0.15 melanoma) to 2018 (0.16 breast, 0.08 melanoma), while no change was found in the proportion of brain metastases from lung, renal, and colorectal cancers. Brain metastases arising from rare primary sites, defined as those comprising at most 2% of all brain metastases, increased by 34.4% (p = 0.005). Limited sample size prohibited trend analysis of other individual primary sites. We report a decrease over 11 years in the proportion of brain metastases originating from breast cancer and melanoma at our institution, and an increase in brain metastases from rare primary sites. Further work with larger, multi-center databases will enable additional evaluation of brain metastases from rare primary sites., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Leptomeningeal carcinomatosis is a devastating consequence of late-stage cancer, and despite multimodal treatment, remains rapidly fatal. Definitive diagnosis requires identification of malignant cells in the cerebrospinal fluid (CSF), or frank disease on MRI. Therapy is generally palliative and consists primarily of radiotherapy and/or chemotherapy, which is administered intrathecally or systemically. Immunotherapies and novel experimental therapies have emerged as promising options for decreasing patient morbidity and mortality. In this review, the authors discuss a refined view of the molecular pathophysiology of leptomeningeal carcinomatosis, current approaches to disease management, and emerging therapies., Competing Interests: Disclosure The authors have no conflicts of interest to report. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. M.H. Gephart’s salary is supported in part by NIH grant K08 NS901527., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Cannabis is the most commonly used drug in the United States; however, the effects of cannabis use on male sexual function are poorly understood., Aim: To characterize the contemporary landscape of cannabis use and to assess the associations between male sexual function and the frequency of use, the primary method of consumption, or cannabis chemovar (tetrahydrocannabinol or cannabidiol) among current users., Methods: We surveyed adults who visited a single cannabis dispensary for baseline demographic information, medical history, cannabis use habits, and sexual function as assessed by the International Index of Erectile Function (IIEF). An IIEF-5 < 21 was considered erectile dysfunction., Main Outcome Measures: The main outcome measure of the study was male sexual function via the IIEF domain scores., Results: A total of 325 men completed the survey with a mean age of 46.7 years. 71.1% of the men were Caucasian and 52.6% were married. 13 men (4%) were never users; 29 men (8.9%) used 1-2 times/week; 51 men (15.7%) used 3-5 times/week, and 232 men (71.4%) used 6+ times/week. The average IIEF-5 score was 22.3 with 19.4% of the men having erectile dysfunction. In univariate analysis, men using cannabis more frequently had a higher overall IIEF (65.36 vs 60.52, P = .001), erectile domain (27.32 vs 25.74, P = .03), orgasm domain (9.08 vs 8.12, P < .001), intercourse satisfaction domain (12.42 vs 11.31, P = .006), and overall satisfaction domain (8.11 vs 7.05, P = .002). In multivariable analysis, compared to men who used cannabis 0 times/week, those who used 6 times/week had an increased overall IIEF (69.08 vs 64.64, P-value adjusted = 0.02), intercourse satisfaction domain (P-value adjusted = 0.04), and overall satisfaction domain (P-value adjusted = 0.02). The primary method of consumption (eg, smoking, edibles, etc.) and cannabinoid composition (eg, cannabidiol vs tetrahydrocannabinol dominant) were not associated with sexual function., Conclusion: We report an association between the increased frequency of cannabis use and increased male sexual function. However, while the increased frequency of use was statistically significant with regard to the IIEF scores, the clinical significance of this is likely low, and selection bias may limit the generalizability of these findings. The method of consumption and cannabis chemovar were not associated with sexual function. Bhambhvani HP, Kasman AM, Wilson-King G, et al. A Survey Exploring the Relationship Between Cannabis Use Characteristics and Sexual Function in Men. J Sex Med 2020;8:436-445., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Pediatric cancer survivors suffer indirect long-term effects of their disease; however, there is a paucity of data regarding the effect of pediatric cancer survivorship on sexual function., Aim: To assess the prevalence and risk factors associated with sexual dysfunction among pediatric cancer survivors., Methods: Pediatric cancer survivors were recruited to complete an online survey using the Female Sexual Function Index (FSFI) or the International Index of Erectile Function (IIEF-5), both validated questionnaires to assess female sexual dysfunction (FSD) and erectile dysfunction (ED). Patient demographics, oncologic history, prior treatment, and sexual habits were also queried. Logistic regression was used to evaluate risk factors for sexual dysfunction, and Mann-Whitney U test was used to identify factors associated with individual domains of the FSFI., Outcomes: The main outcome measures were FSFI and IIEF-5 score, which are used to diagnose FSD (FSFI<26.55) and ED (IIEF-5<22)., Results: A total of 21 (72.4%) female respondents and 20 (71.4%) male respondents were sexually active and completed the survey and FSFI or IIEF-5 questionnaire, respectively. Mean (±SD) age was 23.7 (4.1) years, and average age at diagnosis was 9.1 (5.0), with no difference between genders. Overall, 25.0% (5/20) of male and 52.4% (11/21) of female pediatric cancer survivors reported sexual dysfunction (P = .11). Oncologic history and prior treatment were not associated with sexual function. Females who reported difficulty relaxing during intercourse in the last 6 months had higher odds of reporting sexual dysfunction (odds ratio: 13.6, 95% confidence interval: 1.2-151.2, P = .03). Subgroup analysis of FSFI domains found that previous radiation therapy was correlated with decreased lubrication and satisfaction during intercourse, whereas previous treatment to the pelvic region significantly reduced satisfaction and increased pain during intercourse., Clinical Implications: Female pediatric cancer survivors have higher odds of reporting sexual dysfunction after treatment and should be screened appropriately to provide early intervention and to mitigate risk., Strength & Limitations: Our study includes validated questionnaires to assess FSD and ED and queries specific characteristics to assess their association with sexual dysfunction. However, the study is limited by sample size and its cross-sectional survey design., Conclusions: The prevalence of female sexual dysfunction in this cohort is higher than that in the general population of equivalent-aged individuals, and clinicians should be aware of these potential long-term sequelae. Greenberg DR, Khandwala YS, Bhambhvani HP, et-al. Male and Female Sexual Dysfunction in Pediatric Cancer Survivors. J Sex Med 2020;17:1715-1722., (Copyright © 2020 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Migraine headache is a common condition with an estimated lifetime prevalence of greater than 20%. While it is a well-established risk factor for cardiovascular disease and ischemic stroke, its association with subarachnoid hemorrhage is largely unexplored. We sought to compare the incidence of aneurysmal subarachnoid hemorrhage in a cohort of migraine patients with a cohort of patients with tension headache. A cohort comparison study utilizing the MarketScan insurance claims database compared patients diagnosed with migraine who were undergoing treatment with abortive or prophylactic pharmacotherapy (treatment cohort) and patients diagnosed with tension headache who had never been diagnosed with a migraine and who were naïve to migraine pharmacotherapy (control cohort). Patients with major pre-existing risk factors for aSAH were excluded from the study, and minor risk factors such as smoking status and hypertension were accounted for using coarsened exact matching (CEM) and subsequent cox proportional-hazards (CPH) regression. More than 679,000 patients (~125,000 treatment and ~ 550,000 control) with an average follow-up of more than three years were analyzed for aneurysmal subarachnoid hemorrhage. CPH regression on matched data showed that treated migraine patients had a significantly lower hazard of aneurysmal subarachnoid hemorrhage compared with tension headache patients (HR = 0.40, 95% CI: 0.19 - 0.86, p = 0.02). This large cohort comparison study, analyzing more than 679,000 patients, demonstrated that migraine patients undergoing pharmacologic treatment had a lower hazard of aneurysmal subarachnoid hemorrhage than patients diagnosed with tension headaches. Future work specifically focusing on migraine medications may identify the mechanisms underlying this association., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Prevalence and bother of ejaculatory dysfunction (EjD) has yet to be evaluated in a men's health referral population., Aim: To evaluate the prevalence and associated risk factors of EjD in men presenting to a men's health clinic., Methods: A retrospective review examined patients presenting to an outpatient men's health clinic who completed the Sexual Health Inventory for Men and the Male Sexual Health Questionnaire Ejaculatory Dysfunction (MSHQ-EjD) Short Form. Patient factors including demographics, comorbidities, and medication were examined. Descriptive statistics and multivariable logistic regression were used., Main Outcome Measures: The main outcomes of this study are Sexual Health Inventory for Men and MSHQ-EjD scores., Results: A total of 63 (24%) of patients presenting to the urology clinic were characterized as having EjD based on questionnaire responses. The mean age for men with EjD was 53.8 years, while those without was 42.6 years (P < .001). Of men with EjD, 74.6% were at least moderately bothered (MSHQ-EjD ≥3). Men with EjD were more likely to have erectile dysfunction (77.8%) compared with those without (21%, P < .001) as well as a history of a pelvic cancer (20.6% vs 6%, P = .001). On multivariable regression, erectile dysfunction (odds ratio: 15.04, 95% confidence interval: 6.76-35.92, P < .0001) and alpha inhibitor prescription (odds ratio: 6.82, 95% confidence interval: 1.57-30.16, P = .01) were associated with a higher odds of EjD. ED was found to be a mediator of the relationship between EjD and age, as the age association was lost in the ED population on multivariable regression compared with the non-ED population where it remained significant., Conclusions: EjD is common among patients presenting to a men's health clinic and may present at varying ages, though it is more common in those aged 50 years or older; it is independent of age and race. EjD is associated with erectile dysfunction, pelvic cancer history, and use of alpha inhibitors, presenting a population that could be considered for screening. Kasman AM, Bhambhvani HP, Eisenberg ML. Ejaculatory Dysfunction in Patients Presenting to a Men's Health Clinic: A Retrospective Cohort Study. J Sex Med 2020;8:454-460., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Brain metastases (BMs) from hepatocellular carcinoma (HCC) are rare, with a paucity of reported cases. In the present retrospective cohort report, we assessed the proportion of BMs arising from HCC and characterized the related details, including patient demographics, clinical characteristics, treatment modalities, and survival outcomes., Methods: We retrospectively identified and reviewed the medical records of 14 patients with BMs from HCC seen at our institution from 2008 to 2018., Results: Among all patients with BMs, the proportion originating from primary liver cancer was 0.39%. In every case (n = 14), the liver cancer was HCC. The median age at the BM diagnosis was 64 years (range, 37-82 years). The median alpha-fetoprotein level at the diagnosis of BM was 540 ng/mL (range, 3-10,000 ng/mL). The median interval from the HCC diagnosis to the development of BMs was 31.1 months (range, 3.17-107 months). Of the 14 patients, 8 (57%) had had metastases to the brain parenchyma and 6 had had skull or dural metastases. For patients with brain parenchymal metastases, the median number of metastases was 1 (range, 1-5). Of the 14 patients, 13 have died, with a median overall survival after the BM diagnosis of 2.83 months (range, 0.430-24.0 months). At the latest follow-up examination, the survival for the 14th patient was 142 months after the BM diagnosis. Resection of BMs with radiosurgery was associated with increased survival compared with radiosurgery alone (10.9 months vs. 2.8 months; P = 0.04)., Conclusions: HCC BMs are rare and constitute a small fraction of the total incidence of BMs. The prognostic data we have provided can aid medical providers in caring for patients with HCC BMs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Brain metastases from prostate cancer are rare and poorly described. We sought to assess the proportion of brain metastases arising from prostate cancer and to detail clinical characteristics, treatment modalities, and survival outcomes., Methods: We retrospectively identified and reviewed the charts of 31 patients with intraparenchymal brain metastases from prostate adenocarcinoma seen at our institution from 2008 to 2018., Results: Among all patients with brain metastases, the proportion originating from prostate adenocarcinoma was 0.86%. The median age at the time of brain metastasis diagnosis was 69 (range, 57-90). The median original Gleason score was 8 (range, 6-10), and the median prostate-specific antigen at the time of brain metastasis was 60 ng/mL (range, 0.34-4600). The median months from initial cancer diagnosis to brain metastasis was 81 (range, 3-195). The median number of brain metastases was 2 (range, 1-5). Patients had concurrent metastases to bone (100%), lung (48%), and liver (35%). Median overall survival was 3 months (range, 0.4-25.0). Treatment of the brain metastases was correlated with an increase in median survival from 1.2 months to 4.6 months with radiosurgery (hazard ratio = 0.11, P = 0.001) and surgical resection plus radiotherapy to 13 months (hazard ratio = 0.05, P < 0.001). All patients died of advanced, systemic disease and not of their intracranial disease., Conclusions: Brain metastasis from prostate cancer constitutes a small fraction of total brain metastases, but is associated with poor prognosis and is seen in the setting of advanced, castrate resistant disease. These data enable treating physicians to appropriately counsel their patients with prostate adenocarcinoma brain metastasis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Though meningioma is the most common primary brain tumor, there is a paucity of epidemiologic studies investigating disparities in treatment and patient outcomes. Therefore, we sought to explore how sociodemographic factors are associated with rates of gross total resection (GTR) and radiotherapy as well as survival., Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database was queried to identify adult patients with meningioma diagnosed between 2005 and 2015. Socioeconomic status (SES) was determined using a validated composite index in which patients were stratified into tertiles and quintiles. Multivariable logistic regression and Cox proportional hazards analyses were used to identify predictors of treatment and survival, respectively., Results: 71,098 patients met our inclusion criteria. Low SES quintile was associated with reduced odds of receiving GTR (OR 0.76, 95% CI 0.69-0.83, p < 0.0001) and radiotherapy (OR 0.83, 95% CI 0.76-0.91, p < 0.0001) as well as worse survival (HR 1.48, 95% CI 1.41-1.56) as compared to the highest SES quintile. Black patients had reduced odds of GTR (OR 0.74, 95% CI 0.67-0.71, p < 0.0001) and worse survival (HR 1.23, 95% CI 1.18-1.29, p < 0.0001) as compared to white patients., Conclusions: This national study of patients with meningioma found socioeconomic status and race to be independent inverse correlates of likelihood of GTR, radiotherapy, and survival. Limited access to care may underlie these disparities in part, and future studies are warranted to identify specific causes for these findings.

Objectives: To assess the effectiveness of a clinical decision support tool consisting of an electronic medical record best practice alert (BPA) on the frequency of lumbar imaging in patients with acute low back pain in the ambulatory care setting, and to explore why providers order imaging outside of clinical guidelines., Methods: On March 23, 2016, we implemented a BPA pop-up alert that informed the ordering physician of the Choosing Wisely recommendation to not order imaging within the first 6 weeks of low back pain in the absence of red flags. We calculated imaging rates 1 year before and after implementation of the BPA. To override the BPA, providers could ignore the alert or explain their rationale for ordering imaging using either preset options or a free-text submission. We tracked preset options and manually reviewed 125 free-text submissions., Results: Significant decreases in both total imaging rate (9.6% decrease; P = 0.02) and magnetic resonance imaging rate (14.9% decrease; P < 0.01) were observed after implementation of the BPA. No change was found in the rates of X-ray or computed tomography scan orders. Almost two-thirds (64%) of the providers used preset options in overriding the BPA, and 36% of the providers entered a free-text submission. Among those providers using a free-text submission, 56% entered a non-guideline-supported rationale., Conclusions: The present study demonstrates the effectiveness of a simple, low-cost clinical decision support tool in reducing imaging rates for patients with acute low back pain. We also identify reasons why providers order imaging outside of clinical guidelines., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Purpose- Deep vein thrombosis (DVTs) is a common disease with high morbidity if it progresses to pulmonary embolus (PE). Anticoagulation is the treatment of choice; warfarin has long been the standard of care. Early experience with direct oral anticoagulants (DOACs) suggests that these agents may be may be a safer and equally effective alternative in the treatment of DVT/PE. Nontraumatic intracranial hemorrhage (ICH) is one of the most devastating potential complications of anticoagulation therapy. We sought to compare the rates of ICH in patients treated with DOACs versus those treated with warfarin for DVT/PE. Methods- The MarketScan Commercial Claims and Medicare Supplemental databases were used. Adult DVT/PE patients without known atrial fibrillation and with prescriptions for either a DOAC or warfarin were followed for the occurrence of inpatient admission for ICH. Coarsened exact matching was used to balance the treatment cohorts. Cox proportional-hazards regressions and Kaplan-Meier survival curves were used to estimate the association between DOACs and the risk of ICH compared with warfarin. Results- The combined cohort of 218 620 patients had a median follow-up of 3.0 months, mean age of 55.4 years, and was 52.1% women. The DOAC cohort had 26 980 patients and 8 ICH events (1.0 cases per 1000 person-years), and the warfarin cohort had 191 640 patients and 324 ICH events (3.3 cases per 1000 person-years; P<0.0001). The DOAC cohort had a lower hazard ratio for ICH compared with warfarin in both the unmatched (hazard ratio=0.26; P=0.0002) and matched (hazard ratio=0.20; P=0.0001) Cox proportional-hazards regressions. Conclusions- DOACs show superior safety to warfarin in terms of risk of ICH in patients with DVT/PE.

Recent reports suggest abnormalities in the regulation of actin cytoskeletal dynamics in schizophrenia, despite consistent evidence for normal actin expression. We hypothesized that this may be explained by changes in the polymerization state of actin, rather than in total actin expression. To test this, we prepared filamentous actin (F-actin, polymeric) and globular actin (G-actin, monomeric) fractions from postmortem anterior cingulate cortex from 16 patients with schizophrenia and 14 comparison subjects. Additionally, binding of fluorescently-labeled phalloidin, a selectively F-actin-binding peptide, was measured in unfractionated samples from the same subjects. Western blot analysis of fractions revealed decreased F-actin, increased G-actin, and decreased ratios of F-actin/total actin and F-actin/G-actin in schizophrenia. Decreased phalloidin binding to F-actin in parallel experiments in the same subjects independently supports these findings. These results suggest a novel aspect of schizophrenia pathophysiology and are consistent with previous evidence of reduced dendritic spine density and altered synaptic plasticity in schizophrenia, both of which have been linked to cytoskeletal abnormalities.

Schizophrenia is a severe psychiatric disorder that is characterized by a wide array of symptoms and a complex neuropathology. A well-characterized neurobiological feature of schizophrenia is abnormal synaptic plasticity, although the mechanisms underlying this are not fully understood. Numerous studies have demonstrated a link between proper functioning of the cytoskeleton and synaptic plasticity. The actin-related protein-2/3 (Arp2/3) complex is responsible for the nucleation of new actin filaments and elongation of existing actin filaments and is thus crucial to cytoskeletal dynamics, especially actin polymerization and organization. To determine whether the Arp2/3 complex is abnormally expressed in schizophrenia, we measured the protein expression of Arp2 and Arp3, as well as Arp2/3 complex binding partners and associated proteins including cortactin, neuronal-Wiskott-Aldrich syndrome protein (WASP), WASP-family verprolin homologous protein 1 (WAVE1), and Abelson interactor 1 (Abi1) in the superior temporal gyrus of paired schizophrenia and comparison participants. No changes were found in Arp2, Arp3, neuronal-WASP, WAVE1, or Abi1. However, all three isoforms of cortactin were decreased in schizophrenia. Specifically, the 62 kDa isoform was decreased by 43%; the 71 kDa isoform was decreased by 32%; and the 58 kDa isoform was decreased by 35%. Cortactin regulates branching of filamentous actin through its binding and activation of the Arp2/3 complex, and it is thus critical to the formation of stable actin networks. These findings contribute to a growing body of evidence implicating altered cytoskeletal dynamics in schizophrenia.