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BackgroundUnmarried women who report less recent sexual intercourse (>30 days from survey enumeration) are largely excluded from global health monitoring and evaluation efforts. This study investigated level and contextual factors in modern contraceptive utilization and unmet need within this overlooked female subpopulation in Kenya from 2014 to 2019.MethodsThis study analyzed data from the Performance Monitoring and Accountability (PMA) survey in Kenya, a nationally representative survey of female respondents, to understand the level and contextual factors for family planning utilization and unmet need within female subgroups including married, unmarried sexually active (defined as sexual intercourse within 30 days of survey enumeration), and unmarried with less recent sexual intercourse (defined as sexual intercourse 1-12 months prior to survey enumeration). The analysis included multilevel regression modeling to assess correlates on outcomes of modern contraceptive prevalence rate (mCPR), unmet need, and recent emergency contractive pill (ECP) use, which is a unique PMA question: "Have you used emergency contraception at any time in the last 12 months?".ResultsCumulatively, the surveys enumerated 19,161 women and this weighted analysis included 12,574 women aged 15-49 from three female subgroups: 9,860 married women (78.4%), 1,020 unmarried sexually active women (8.1%), and 1,694 unmarried women with less recent sexual intercourse (13.5%). In 2019, while controlling for covariates, unmarried women with less recent sexual intercourse exhibited statistically significant differences (p-valueConclusionIn Kenya, unmarried women with less recent sexual intercourse exhibited significantly different contraceptive utilization, unmet need, and recent emergency contraceptive use. Moreover, changes over time in key family planning indicators were asymmetrical by female subgroup. This study identifies an important monitoring gap regarding unmarried women with less recent sexual intercourse. Evidence dissemination by the global measurement community for these unmarried women is exceedingly scarce; therefore, developing an inclusive research agenda and actionable information about these marginalized women is needed to enable targeted planning and equitable service delivery.

Lyme disease (also known as Lyme borreliosis) is the most common vector-borne disease in the United States with an estimated 476,000 cases per year. While historically, the long-term impact of Lyme disease on patients has been controversial, mounting evidence supports the idea that a substantial number of patients experience persistent symptoms following treatment. The research community has largely lacked the necessary funding to properly advance the scientific and clinical understanding of the disease, or to develop and evaluate innovative approaches for prevention, diagnosis, and treatment. Given the many outstanding questions raised into the diagnosis, clinical presentation and treatment of Lyme disease, and the underlying molecular mechanisms that trigger persistent disease, there is an urgent need for more support. This review article summarizes progress over the past 5 years in our understanding of Lyme and tick-borne diseases in the United States and highlights remaining challenges.

# Background In 2012, the UN Commission on Life Saving Commodities (UNCoLSC) articulated a series of recommendations to expand access to 13 life-saving reproductive, maternal, newborn and child health (RMNCH) commodities with the greatest potential to reduce preventable deaths. We conducted a five-year longitudinal assessment of progress towards achieving these recommendations among countries in sub-Saharan Africa and Southeast Asia. # Methods Between 2013 and 2017, national reviews were undertaken at two time points among 14 countries with a high burden of preventable maternal-child deaths who were receiving support from a multi-UN agency RMNCH technical support and financing mechanism. Data were drawn from national health documentation (e.g. strategic plans, policies, guidelines); logistics management information systems; national household and health facility surveys; and interviews with governments and development partners. # Results Over time, the percent of health facilities with stock availability showed a statistically significant increase of five percentage points from 69% to 74% (median). Recent training at health facility also displayed a significant increase of eight percentage points from 38% to 46% (median). National RMNCH coordination mechanisms, treatment guidelines, and national training curricula and job-aids were near fully redressed. However, countries continue to face persistent supply chain challenges including national stock-outs, tracking commodities throughout the supply chain, and strengthening medicine control laboratories. # Conclusions While substantial progress has been made in improving access to life-saving commodities, including stock availability and workforce training at health facilities, additional efforts are required to improve regulatory efficiency, enhance commodity quality and safety, and reduce supply chain fragmentation.

Background: In September, 2012, the UN Commission on Life Saving Commodities (UNCoLSC) outlined a plan to expand availability and access to 13 life saving commodities. We profile global and country progress against these recommendations between 2012 and 2015. Methods: For 12 countries in sub-Saharan Africa that were off-track to achieve the Millennium Development Goals for maternal and child survival, we reviewed key documents and reference data, and conducted interviews with ministry staff and partners to assess the status of the UNCoLSC recommendations. The RMNCH fund provided short-term catalytic financing to support country plans to advance the commodity agenda, with activities coded by UNCoLSC recommendation. Our network of technical resource teams identified, addressed, and monitored progress against cross-cutting commodity-related challenges that needed coordinated global action. Findings: In 2014 and 2015, child and maternal health commodities had fewer bottlenecks than reproductive and neonatal commodities. Common bottlenecks included regulatory challenges (ten of 12 countries); poor quality assurance (11 of 12 countries); insufficient staff training (more than half of facilities on average); and weak supply chains systems (11 of 12 countries), with stock-outs of priority commodities in about 40% of facilities on average. The RMNCH fund committed US$175·7 million to 19 countries to support strategies addressing crucial gaps. $68·2 million (39·0%) of the funds supported systems-strengthening interventions with the remainder split across reproductive, maternal, newborn, and child health. Health worker training ($88·6 million, 50·4%), supply chain ($53·3 million, 30·0%), and demand generation ($21·1 million, 12·0%) were the major topics of focus. All priority commodities are now listed in the WHO Essential Medicines List; appropriate price reductions were secured; quality manufacturing was improved; a fast-track registration mechanism for prequalified products was established; and methods were developed for advocacy, quantification, demand generation, supply chain, and provider training. Slower progress was evident around regulatory harmonisation and quality assurance. Interpretation: Much work is needed to achieve full implementation of the UNCoLSC recommendations. Coordinated efforts to secure price reductions beyond the 13 commodities and improve regulatory efficiency, quality, and supply chains are still needed alongside broader dissemination of work products. Funding: Governments of Norway (NORAD) and the UK (DFID).

Multidrug-resistant tuberculosis (MDR TB) in Africa may be more prevalent than previously appreciated. Factors leading to development of drug resistance need to be understood to develop appropriate control strategies for national programs. We gathered estimates of MDR TB rates for 39 of 46 countries in Africa. The relationship between MDR TB rates and independent factors was analyzed by using correlation and linear regression models. Our findings indicate that drug resistance surveys in Africa are critically needed. MDR TB rates must be assessed in countries without these surveys. In countries that have conducted a drug resistance survey, a new survey will determine evolution of drug resistance rates. We found no correlation between high MDR rates and TB incidence, HIV/TB co-infection rates, or year of introduction of rifampin. Results show that the retreatment failure rate was the most predictive indicator for MDR TB. Current category II drug regimens may increase MDR TB.

INTRODUCTION: Ziehl-Neelsen (ZN) bright-field microscopy is time-consuming, with poor sensitivity, even under optimal conditions. Introduction of Primo StariLED fluorescent microscopy (FM) may improve TB case finding at referral hospitals in Rwanda.The study aimed to determine the acceptability and effectiveness of iLED in a low resource setting. METHODS: between June 2009 and May 2010, the Rwandan TBProgramand National Reference Laboratorycarried out demonstration studies with iLED at a referral hospital in the capital,Kigali, and a rural district hospital in Nyamata, takingconventional FM as Gold Standard. RESULTS: agreement between the iLED and rechecking at the Reference Laboratory were deemed �almost perfect� (kappa = 0.81-1.00) across three of four site-phase combinations. The exception was Nyamata District Hospital during the validation phase, which was deemed �substantial�agreement (kappa = 0.61-0.80). However, the 100% concordance at both demonstration sites during the continuation phase shows technicians' rapid command of the new iLED microscope in a relatively short time. The lower overall positivity rate obtained in the rural clinicis not related to the performance of the microscope (or technicians), but is attributable to a significant increase in total number of patients and samples screened through active case finding. CONCLUSIONS: laboratory technicians demonstrated high acceptance ofiLED. Additionally, fluorescent microscopy reduces the time necessary for examination by more than half. The high level of agreement between iLED and FMduring implementation in both sites provides initial evidence for iLED to replace current methods.

The gamma-herpesviruses persist as latent episomes in a dynamic lymphocyte pool. Their consequent need to express a viral episome maintenance protein presents a potential immune target. The glycine-alanine repeat of the Epstein-Barr virus episome maintenance protein, EBNA-1, limits EBNA-1 epitope presentation to CD8+ T lymphocytes (CTLs). However, CTL recognition occurs in vitro, so the significance of such evasion for viral fitness is unclear. We used the murine gamma-herpesvirus-68 (MHV-68) to define the in vivo contribution of cis-acting CTL evasion to host colonisation. Although the ORF73 episome maintenance protein of MHV-68 lacks a glycine-alanine repeat, it was equivalent to EBNA-1 in conferring limited presentation on linked epitopes. This was associated with reduced protein synthesis and reduced protein degradation. We bypassed the cis-acting evasion of ORF73 by using an internal ribosome entry site to express in trans-a CTL target from the same mRNA. This led to a severe, MHC class I-restricted and CTL-dependent reduction in viral latency. Thus, despite MHV-68 encoding at least two trans-acting CTL evasion proteins, cis-acting evasion during episome maintenance was essential for normal host colonisation.

Sarcomas are a rare classification of tumor derived from tissues of mesenchymal origin including bone, fat, muscle, cartilage, and blood vessels. These tumors often grow rapidly and have limited treatment options with few significant therapeutic advances in recent years. Liposarcomas (LPSs), the most common type of malignant soft tissue sarcoma, are derived from mesenchymal progenitors that have undergone an adipogenic lineage commitment compared to their multipotent counterparts. Interestingly, the grade of differentiation within LPS can vary highly, and the differentiation status of these tumors can drastically affect prognosis and likelihood of metastasis, making tumor differentiation a potential mechanism to target in liposarcoma development. Here, we show that overexpression of the Hedgehog transcription factor Gli2 in dedifferentiated liposarcoma (DDLPS) cells represses adipogenic differentiation while simultaneously activating markers of osteoblast differentiation in vitro . In addition, we observed marked differences in cytokine expression and secretion, prompting us to perform orthotopic fat pad injections of control and Gli2 overexpressing DDLPS cells. Using flow cytometry, we observed distinct changes in fat pad macrophage populations, with a particular increase in M2-like macrophages. Taken together, we find that overexpression of Gli2 in DDLPS cells alters their differentiation capacity and interactions between tumor cells and macrophages, highlighting a novel role for this developmental transcription factor in liposarcoma pathogenesis.

The establishment and progression of bone metastatic breast cancer is supported by immunosuppressive myeloid populations that enable tumor growth by dampening the innate and adaptive immune response. Much work remains to understand how to target these tumor-myeloid interactions to improve treatment outcomes. Noncanonical Hedgehog signaling is an essential component of bone metastatic tumor progression, and prior literature suggests a potential role for Hedgehog signaling and its downstream effector Gli2 in modulating immune responses. In this work, we sought to identify if inhibition of noncanonical Hedgehog signaling alters the cytokine profile of osteolytic breast cancer cells and the subsequent communication between the tumor cells and myeloid cells. Examination of large patient databases revealed significant relationships between Gli2 expression and expression of markers of myeloid maturation and activation as well as cytokine expression. We found that treatment with HPI-1 reduced tumor cell expression of numerous cytokine genes, including CSF1 , CSF2 , and CSF3 , as well as CCL2 and IL6 . Secreted CSF-1 (M-CSF) was also reduced by treatment. Changes in tumor-secreted factors resulted in polarization of THP-1 monocytes toward a proinflammatory phenotype, characterized by increased CD14 and CD40 surface marker expression. We therefore propose M-CSF as a novel target of Hedgehog inhibition with potential future applications in altering the immune microenvironment in addition to its known roles in reducing tumor-induced bone disease., Competing Interests: 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., (© 2024 The Authors.)

Social media (SoMe) offers great potential to expand access to health information, but a significant proportion of users consume its content instead of consulting a physician. We sought to quantify the volume and characterize the accuracy of men's health-related content on TikTok and Instagram. We searched TikTok and Instagram for the terms: testosterone, erectile dysfunction, male infertility, semen retention, Peyronie's disease, and vasectomy. The top 10 hashtags for each term were used to estimate the total impressions for each term on each platform, and posts were then characterized by creator type, content type, and accuracy (1 to 5 scale). TikTok had 2,312,407,100 impressions and Instagram had 3,107,300 posts across all topics. Semen retention had the most impressions on TikTok (1,216,074,000) and posts on Instagram (1,077,000). Physicians created only a small portion of total TikTok and Instagram posts (10.3% and 12.9%, respectively). Across all topics, the accuracy of content was poor (2.6 ± 1.7), however, physician posts were more accurate than non-physician posts (mean 4.2 ± 1.2 vs 2.3 ± 1.6, p < 0.001, respectively). Men's health content is popular on TikTok and Instagram but is not accurate. We recommend that physicians actively engage in SoMe to address misinformation., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Low-intensity shockwave therapy (LiSWT) for erectile dysfunction (ED) continues to gain popularity in both clinical practice and the academic literature. The majority of trials and meta-analysis studies have shown LiSWT to be low risk with a trend toward positive improvements in International Index of Erectile Function (IIEF) scores. However, there is still debate over the clinical utility of LiSWT and there is no agreed upon optimal treatment protocol. In this review article we summarize published meta-analysis studies of LiSWT for ED, and review the treatment protocols from randomized sham-control trials published in the last 10 years. We found the most common device settings were an energy of 0.09 mJ/mm² and a frequency of 5 Hz. Shock number and location varied, but the most common protocol was 1,500 shocks per session, with 900 shocks to the penis (shaft, base, or hilum) and 600 shocks to the proximal corpora/crura. Protocols ranged from 4 to 12 treatment sessions. We also describe our institutional experience with LiSWT, including patient counseling and treatment protocol., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Purpose To evaluate the prevalence of elevated blood pressure (EBP), hypertension (HTN), and obesity among men presenting for fertility evaluation. Methods We retrospectively evaluated all men presenting for male infertility consultation at a single institution from 2000 to 2018. Blood pressure (BP) measurements were abstracted from the electronic health record, and EBP/HTN was defined according to American Heart Association/American College of Cardiology guidelines (systolic blood pressure (SBP) ≥ 120 mmHg or diastolic blood pressure (DBP) ≥ 80 mmHg). Descriptive statistics were used to compare demographic and clinical characteristics of men with and without EBP/HTN or obesity (BMI ≥ 30 kg/m 2 ), and logistic regression was utilized to determine associations with EBP/HTN. Results Among 4,127 men, 1,370 (33.2%) had a recorded SBP and DBP within one year of their initial visit. EBP/HTN was noted in 857 (62.6%) men. A total of 249 (18.2%) men were obese, 863 (63.0%) were non-obese, and 258 (18.8%) did not have BMI recorded. HTN and obesity were jointly present in 195 (17.5%) men. There was no significant difference in age, ethnicity, or total motile sperm count between men with and without EBP/HTN. On multivariable analysis, BMI was significantly associated with EBP/HTN (OR: 1.13, 95% CI: 1.08-1.18, p < 0.001). Conclusion More than half of men presenting for initial fertility consultation have either EBP, obesity, or both. Reproductive urologists should consider routinely screening for these conditions and encourage men to seek further evaluation and treatment, when appropriate., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Greenberg et al.)

We sought to characterize the prevalence of sexual dysfunction and barriers to treatment among male physicians. Between June and December 2022, male physicians were invited to complete a questionnaire regarding sexual function. Surveys were disseminated electronically via social media and professional medical societies using Qualtrics (Provo, UT). In totla, 235 responses were included in the final analysis. The mean age of respondents was 36.3 ± 7.4 years (range 23-72). 27 (11.5%) reported having seen a doctor for sexual health. Of these 27, 40.7% saw a physician for erectile dysfunction, 29.6% for low libido, 22.2% for premature ejaculation, 7.4% for delayed ejaculation, and 33.3% for other concerns. An additional 29 (12.3%) considered establishing care for sexual issues but didn't, mostly due to being too busy. 46 (19.6%) respondents reported having taken medication to improve erectile function. Therefore, in a cohort of young male physicians, 23.8% had seen or considered seeing a doctor for sexual health concerns, and nearly 1 in 5 had taken medication for erectile dysfunction. Male physicians appear to be at higher risk for sexual dysfunction than the general population and face significant and unique barriers in access to care for sexual dysfunction., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The characteristics of men who use direct-to-consumer (DTC) men's health services are not well understood. We conducted an online survey of adult men via ResearchMatch, assessing sociodemographic data, health behaviors, and concern for low testosterone and infertility. Logistic regression estimated the association between participant characteristics and familiarity with and reported use of DTC services such as Hims® and Roman®. Among 1276 men surveyed, 62.2% were concerned about low testosterone. While almost half (48.5%) were familiar with men's DTC health services, only 37 (2.9%) reported using these services. On multivariable analysis, men who used DTC men's health services were more likely to be younger (age 18-39: odds ratio [OR] 2.94, 95% confidence interval [CI] 1.03-8.38, p = 0.04; age 40-59: OR 3.26, CI 1.17-9.10, p = 0.02; referent age ≥60), have annual income between $75k and $100k (OR 5.25, CI 1.39-19.87.45, p = 0.02), and be concerned about low testosterone (OR 3.81, CI 1.46-9.96, p = 0.01). In conclusion, younger men and those with mid-range incomes were more likely to use online DTC men's health services compared to older or wealthier men. Likewise, men with concerns about low testosterone were more likely to use DTC services, but other health-conscious behaviors and frequency of doctor visits did not predict use., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Our study sought to evaluate the rates of successful sperm retrieval following microdissection testicular sperm extraction (mTESE) in patients with a prior history of cryptozoospermia, compared to patients with non-obstructive azoospermia (NOA)., Methods: A retrospective chart analysis evaluating all mTESE procedures was performed from January 2004 to August 2018. Inclusion criteria involved all males >18 years of age with a diagnosis of cryptozoospermia and/or NOA that underwent a mTESE. The patient's genetic profile, hormonal profile, semen analysis, testicular volumes, pathology and comorbidities were analyzed., Results: We identified 40 patients with cryptozoospermia and 221 patients with NOA. Successful mTESE occurred in 34/40 (85%) cryptozoospermic males compared to 104/221 (48%) NOA males ( p < 0.001). In univariate and multivariate analyses, patients with cryptozoospermia were more likely to undergo a successful mTESE than patients with NOA (OR 5.56 [1.79-17.29], p = 0.003; OR 5.41 [1.94-15.08], p = 0.0013), respectively. Factors that were associated with a statistically significant lower chance of successful mTESE included Sertoli-cell only pathology, pre-operative testosterone < 300 ng/dL and FSH > 7.6 mIU/mL., Conclusion: Despite patients with a history of cryptozoospermia having a significantly higher chance of a successful sperm retrieval than patients with NOA, couples should be counselled on the possibility of an unsuccessful sperm extraction, in order to optimize the pre-operative IVF planning and to manage operative expectations.

Objective: To investigate whether the minimal cyclophosphamide equivalent dose (mCED), a novel approach for estimating alkylating agent exposure, is associated with the sperm retrieval rates by microdissection testicular sperm extraction (mTESE) in azoospermic postchemotherapy cancer survivors., Design: A retrospective cohort study conducted between 2002 and 2017., Setting: An academic medical center., Patients: A total of 28 azoospermic postchemotherapy cancer survivors who underwent mTESE., Interventions: Chemotherapy exposure and mCED calculation., Main Outcome Measures: The primary outcome was the association between the mCED and sperm retrieval rate using mTESE. The mCED value for each patient's regimen received was estimated using the lowest recommended dosing regimen from the range of recommended doses at the time of administration., Results: Spermatozoa were successfully retrieved in 11 (39.3%) of the patients. Age at the time of receiving chemotherapy and mCED were significant factors associated with sperm retrieval. An mCED of <4,000 mg/m 2 had a higher sperm retrieval rate (10/14, 71.4%) than an mCED of >4,000 mg/m 2 (0/8, 0). The hormone levels were not significantly different when comparing patients with and without successful sperm retrieval. Seminoma, nonseminomatous germ cell tumor, and acute lymphoblastic leukemia had favorable sperm retrieval rates-100% (2/2), 66.7% (2/3), and 66.7% (2/3), respectively-although the numbers of patients in each group were small., Conclusion: Among this cohort of patients with cancer who required chemotherapy regimens, successful sperm retrieval by mTESE was only noted among cancer survivors receiving an mCED of <4,000 mg/m 2 ., Competing Interests: I-S.H. has nothing to disclose. R.J.F. has nothing to disclose. J.A.H. has nothing to disclose. J.W. has nothing to disclose. N.E.B. has nothing to disclose. M.N.P. has nothing to disclose. A.S. has nothing to disclose. W.J.H. has nothing to disclose. R.E.B. has nothing to disclose., (© 2023 The Authors.)

Due to the cellular plasticity that is inherent to cancer, the acquisition of resistance to therapy remains one of the biggest obstacles to patient care. In many patients, the surviving cancer cell subpopulation goes on to proliferate or metastasize, often as the result of dramatically altered cell signaling and transcriptional pathways. A notable example is the Hedgehog (Hh) signaling pathway, which is a driver of several cancer subtypes and aberrantly activated in a wide range of malignancies in response to therapy. This review will summarize the field's current understanding of the many roles played by Hh signaling in drug resistance and will include topics such as non-canonical activation of Gli proteins, amplification of genes which promote tolerance to chemotherapy, the use of hedgehog-targeted drugs and tool compounds, and remaining gaps in our knowledge of the transcriptional mechanisms at play., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Miller, Bennett and Rhoades.)

Objective: To compare the prevalence of abnormal hormone parameters among men with and without oligospermia to determine the value of universal hormonal screening during initial fertility evaluation., Materials and Methods: We retrospectively evaluated men who underwent semen analysis and hormonal evaluation (morning testosterone [T] and follicle-stimulating hormone [FSH]) between January 2002 and May 2021. Sperm concentration was dichotomized at 15 million/mL according to World Health Organization (WHO) criteria. We compared median and interquartile range (IQR) T and FSH levels according to sperm concentration using Kruskal-Wallis test. Differences in prevalence of low testosterone (<300 ng/dL) and abnormal FSH (>7.6mIU/mL) were determined using chi-square test., Results: 1164 men had a morning serum T. There was no difference in median T among men with normal vs abnormal sperm concentration (316 ng/dL, IQR 250-399 vs 316 ng/dL, IQR 253-419; P = .52). FSH was measured in 1261 men. Median FSH was higher among men with sperm concentration <15 million/mL (6.0IU/mL, IQR 3.9-10.7 vs 3.8IU/mL, IQR 2.7-5.7; P < .001). Among men with ≥15 million/mL concentration, 44.1% were found to have low T (P = .874) and 10.8% had an FSH ≥7.6 mIU/mL (P < .001). Among men with ≥15 million/mL sperm concentration who underwent both T and FSH evaluation, 43.6% had at least 1 hormonal abnormality., Conclusion: Almost half of men with normal sperm concentration had low T. As low T may have long-term implications for both fertility and overall health, providers should consider universal T screening in men presenting for fertility evaluation., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Liposarcomas are the most diagnosed soft tissue sarcoma, with most cases consisting of well-differentiated (WDLPS) or dedifferentiated (DDLPS) histological subtypes. While both tumor subtypes can have clinical recurrence due to incomplete resections, DDLPS often has worse prognosis due to a higher likelihood of metastasis compared to its well-differentiated counterpart. Unfortunately, targeted therapeutic interventions have lagged in sarcoma oncology, making the need for molecular targeted therapies a promising future area of research for this family of malignancies. In this work, previously published data were analyzed to identify differential pathways that may contribute to the dedifferentiation process in liposarcoma. Interestingly, Gli-mediated Hedgehog signaling appeared to be enriched in dedifferentiated adipose progenitor cells and DDLPS tumors, and coincidentally Gli1 is often co-amplified with MDM2 and CDK4, given its genomic proximity along chromosome 12q13-12q15. However, we find that Gli2, but not Gli1, is differentially expressed between WDLPS and DDLPS, with a noticeable co-expression signature between Gli2 and genes involved in ECM remodeling. Additionally, Gli2 co-expression had a noticeable transcriptional signature that could suggest Gli-mediated Hedgehog signaling as an associated pathway contributing to poor immune infiltration in these tumors.

When breast cancer metastasizes to bone, treatment options are limited. Failure to treat bone metastases is thought to be due to therapy-resistant features of the bone marrow microenvironment. Using a murine model of bone metastatic mammary carcinoma, we demonstrate that systemic delivery of polymer nanoparticles loaded with cyclic dinucleotide (CDN) agonists of stimulator of interferon genes (STING) inhibited tumor growth and bone destruction after 7 days of treatment. Each dose of STING-activating nanoparticles trafficked to the bone marrow compartment and was retained within the tumor microenvironment for over 24 hours, enhancing antitumor immunity through proinflammatory cytokine production and early T-cell activation. While acquired resistance mechanisms, including increased levels of immunosuppressive cytokines and the infiltration of regulatory T cells, ultimately limited antitumor efficacy after 2 weeks of treatment, bone protective effects remained. Overall, these studies demonstrate that STING pathway activation, here enabled using a nanomedicine approach to enhance CDN delivery to bone metastatic sites, can reprogram the immune contexture of the bone marrow to an antitumor phenotype that inhibits bone colonization of metastatic breast cancer cells and protects from tumor-mediated bone destruction., Significance: Bone metastases are difficult to treat due to the inaccessibility of the bone marrow compartment and the immunosuppressive microenvironment that protects resident stem cells. Packaging a STING agonist into a nanoparticle that enables systemic administration and drug accumulation at tumor sites overcomes both barriers to stymie metastatic breast cancer growth., Competing Interests: N.E. Bennett reports grants from NIH during the conduct of the study. A.R. Merkel reports grants from Verteran's Administration and non-financial support from Vanderbilt University Medical Center during the conduct of the study; grants from NIH Clinical and Translational Science Award and National Center for Advancing Translational Sciences outside the submitted work. M.A. Fischer reports grants from Incyte Corporation during the conduct of the study. M.R. Savona reports grants from ALX Oncology, Astex, Incyte, Takeda, TG Therapeutics; personal fees from BMS, CTI, Forma, Geron, Novartis, Sierra Oncology, Taiho; personal fees and other from Ryvu and Karyopharm outside the submitted work. J.A. Rhoades reports grants from Veterans Administration during the conduct of the study. S.A. Guelcher reports grants from Incyte Corporation during the conduct of the study. J.T. Wilson reports a patent to 10,696,985 issued and a patent to PCT/US2019/058945 pending. No disclosures were reported by the other authors., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Direct-to-consumer genetic services allow companion animal guardians to purchase a DNA test and receive detailed results about their pet's ancestry, health, and traits results. In collaboration with Wisdom Panel, we present novel findings about consumer motivations, perceptions, and responses to their use of canine genomic services. Wisdom Panel customers were invited to complete an online survey anonymously in which they were asked about their reasons for using a genetic test for their dog, how they perceived the test's results, and how they responded to the results they received. Participant data revealed most utilized a test that provided more ancestry/breed results (75.9%) as compared to health-related results. The majority of participants perceived the breed test results as accurate (52.0% strongly agree, 27.6% somewhat agree) and the genetic services provided as having great value (49.6% strongly agree, 32.7% somewhat agreed). In responding to their dog's results, participants indicated they shared the information with family (88.1%) and friends (84.2%). Collectively, our study indicates consumers are more focused on their dog's ancestry than other test results. Using these findings and previous literature on human direct-to-consumer genetic testing, human-animal dyads, and identity construction, we consider the possibility of "breed options theory" and future areas of research.

Purpose: Priapism is a persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation and results in a prolonged and uncontrolled erection. Given its time-dependent and progressive nature, priapism is a situation that both urologists and emergency medicine practitioners must be familiar with and comfortable managing., Methodology: A comprehensive search of the literature on acute ischemic priapism and non-ischemic priapism (NIP) was performed by Emergency Care Research Institute for articles published between January 1, 1960 and May 1, 2020. A search of the literature on NIP, recurrent priapism, prolonged erection following intracavernosal vasoactive medication, and priapism in patients with sickle cell disease was conducted by Pacific Northwest Evidence-based Practice Center for articles published between 1946 and February 19, 2021. Searches identified 4117 potentially relevant articles, and 3437 of these were excluded at the title or abstract level for not meeting inclusion criteria. Full texts for the remaining 680 articles were ordered, and ultimately 203 unique articles were included in the report., Results: This Guideline provides a clinical framework for the treatment (non-surgical and surgical) of NIP, recurrent ischemic priapism, and priapism in patients with sickle cell disease. The treatment of patients with a prolonged erection following intracavernosal vasoactive medication is also included. The AUA guideline on the diagnosis of priapism and the treatment of acute ischemic priapism was published in 2021., Conclusions: All patients with priapism should be evaluated emergently to identify the sub-type of priapism (acute ischemic versus non-ischemic) and those with an acute ischemic event should be provided early intervention when indicated. NIP is not an emergency and treatment must be based on patient objectives, available resources, and clinician experience. Management of recurrent ischemic priapism requires treatment of acute episodes and a focus on future prevention of an acute ischemic event. Sickle cell disease patients presenting with an acute ischemic priapism event should initially be managed with a focus on urologic relief of the erection; standard sickle cell assessment and interventions should be considered concurrent with urologic intervention. Treatment protocols for a prolonged, iatrogenic erection must be differentiated from protocols for true priapism.

Objective: To examine the association between selective serotonin reuptake inhibitor (SSRI) use and semen quality., Methods: We performed a retrospective review of all men undergoing semen analysis (SA) for fertility evaluation from 2002-2020 at a single academic medical center. Men were excluded if they had prior exposure to spermatotoxic medications, clomiphene citrate, gonadotropins, selective estrogen receptor modulators, or medical conditions known to impact male fertility. SSRI exposure was defined by an outpatient prescription within 90 days prior to any semen test. Differences between men with and without SSRI exposure were assessed with Wilcoxon rank sum for continuous variables and chi-squared testing for proportions. Univariable and multivariable linear regression models were fit to evaluate the relationship between SSRI use and individual semen parameters, controlling for age at the time of the semen analysis and non-SSRI drug use., Results: A total of 8861 men were identified, of whom 153 men (1.7%) were exposed to SSRIs prior to SA. Median age was 35 years (interquartile range: 32-39) and was similar between groups (P = .999). Non-SSRI medication use was significantly higher in men taking SSRIs (78.4% vs 23.3%, < .001). On univariable and multivariable analyses, SSRI exposure was not associated with differences in semen volume, sperm concentration, motility, total motile sperm count, or normal morphology., Conclusion: In adult men undergoing fertility evaluation, SSRI exposure was not associated with impaired semen parameters. These data may help inform reproductive counseling and medical decision-making regarding SSRI use in men seeking paternity., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To evaluate the predictors of establishing care with a reproductive urologist (RU) among men with abnormal semen analyses (SAs) ordered by nonurologists and examine patient perceptions of abnormal SAs in the absence of RU consultation., Design: Retrospective cohort study with cross-sectional survey., Setting: Large, integrated academic healthcare system during 2002-2019., Patient(s): We identified adult men undergoing initial SAs with nonurologists who had abnormalities. Patients with index SAs during 2002-2018 were included for the analysis of RU consultation. Men tested in 2019 were recruited for cross-sectional survey., Intervention(s): Cross-sectional survey., Main Outcome Measure(s): RU consultation and accurate perception of abnormal SAs., Result(s): A total of 2,283 men had abnormal SAs ordered by nonurologists, among whom 20.5% underwent RU consultation. Mixed-effect logistic regression modeling identified oligospermia as the strongest predictor of RU care (odds ratio, 3.08; 95% confidence interval, 2.43-3.90) with a significant provider-level random intercept. We observed substantial provider-level heterogeneity among nonurologists with provider-specific rates of RU evaluation ranging from 3.7% to 35.8%. We contacted 310 men who did not undergo RU consultation with a 27.2% survey response rate. Of respondents, 6.7% reported receiving an RU referral. Among men with abnormal SAs not evaluated by RU, 22.7% appropriately perceived an abnormal SA., Conclusion(s): In men with abnormal SAs diagnosed by nonurologists, the rate of RU consultation was low and associated with substantial provider-level variation among ordering providers. Patients without RU consultation reported inaccurate perceptions of their SA. Multidisciplinary efforts are needed to ensure that subfertile men receive appropriate RU evaluation., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

This study examined the relationship between stimulant medications used for the treatment of attention deficit hyperactivity disorder and semen parameters. We performed a retrospective cohort study at a large, academic institution between 2002 and 2020. We included men with a semen analysis without prior spermatotoxic medication use, empiric medical therapy exposure or confounding medical diagnoses (varicocele, Klinefelter's syndrome, cryptorchidism, cystic fibrosis, diabetes, cancer or cancer-related treatment, and azoospermia). Men were stratified by stimulant exposure (methylphenidate or amphetamines). A multivariable linear regression was fit to assess the association between individual semen parameters, age, stimulant exposure and non-stimulant medication use. Of 8,861 men identified, 106 men had active prescriptions for stimulants within 90 days prior to semen testing. After controlling for age and exposure to non-stimulant medications, stimulant use was associated with decreased total motile sperm count (β: -18.00 mil/ejaculate and standard error: 8.44, p = 0.033) in the setting of decreased semen volume (β: -0.35 ml, and standard error: 0.16, p = 0.035), but not sperm concentration, motility and morphology. These findings suggest a role for reproductive physicians and mental health providers to consider counselling men on the potential negative impact of stimulants prescribed for attention deficit hyperactivity disorder on semen volume during fertility planning., (© 2021 Wiley-VCH GmbH.)

Purpose of Review: The COVID-19 pandemic has led to devastating health outcomes across the world. Initially thought to primarily affect the respiratory system, there is now clear and abundant evidence that COVID-19 can impact upon the male genitourinary system and overall men's health. In this review article, we explore the potential mechanisms by which COVID-19 specifically affects men and we review the literature examining the adverse effects of the disease on men's health., Recent Findings: Studies suggest that men are at higher risk for severe COVID-19 infection and death. COVID-19 infection has a negative impact on men's health including worsening semen parameters, potentially lower testosterone levels, and an increased risk of erectile dysfunction., Summary: COVID-19 is a highly pathogenic virus that exerts adverse effects upon the male genitourinary system in myriad ways. The COVID-19 infection can impact serum testosterone, fertility, sexual function, and mental health. Fortunately, the COVID-19 vaccine is safe and effective in preventing COVID-19 infection and many of these sequelae., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Mars Petcare introduced the first direct-to-consumer domestic dog genetic test in 2009 and Basepaws introduced the first direct-to-consumer cat genetic test in 2016. Social science research has evaluated numerous aspects of the human direct-to-consumer market, yet no such exploration has evaluated the occurrence of pet owners pursuing pet genetic tests. Using a mixed methods approach, we conducted an exploratory content analysis of direct-to-consumer pet genetic company webpages and consumer reviews shared on Amazon. Initial data reviews indicated some companies may be key industry players, relative to others. Our results present content frequency for each group (key industry players, all other companies), though the primary themes for each remained the same. Analysis showed genetic companies are primarily sharing product and purchasing information, along with trustworthiness to establish the merit of the company and their products. Companies also used statements directed towards pet owners that are suggestive of both pets and "pet parents" benefiting from the test results. The primary themes identified in consumer reviews involved consumers sharing their perception about the tests (e.g., accuracy), what aspects of the test results they focused on (e.g., breed information), and experiences with using the test (e.g., ease of use). Amazon reviews were primarily positive, though the companies with smaller review numbers had higher percentages of negative and ambiguous sentiments. Of interest, reviews most often indicated tests were being used to determine a pet's breed identity, while companies most frequently promoted the health advantages of using their products. Reviews revealed some consumers respond to tests by sharing their pet's results with someone or by altering their pet's care. Considering these results in addition to the growing popularity of this industry and the advancements of genomic technology, further research is needed to determine the role pet genetic testing may have in society and on human-animal relationships., Competing Interests: The authors have declared that no competing interests exist.

Objective: To determine prevalence of hyperprolactinemia and prolactinoma among men presenting for initial fertility evaluation., Methods: We performed a retrospective review of men presenting for initial fertility evaluation at a tertiary care, academic health system between 1999 and 2018. Men with measured prolactin levels were analyzed to determine prevalence of hyperprolactinemia and prolactinoma. We compared clinical characteristics of men with and without hyperprolactinemia. Univariable and multivariable analysis were used to determine factors associated with hyperprolactinemia. We assessed effects of hyperprolactinemia and prolactinoma on testosterone levels, semen parameters and pregnancy outcomes after treatment., Results: A total of 3101 men had serum prolactin level measured. 65 (2.1%) had hyperprolactinemia. Patients with hyperprolactinemia had lower testosterone (median 280 ng/dL vs 313 ng/dL, P = 0.038) and lower total motile sperm count (median 7.0 million vs 34.7 million, P = 0.001) compared to men without hyperprolactinemia. 43.1% of men with hyperprolactinemia had oligospermia vs 21.5% of men without hyperprolactinemia (P<0.001). Univariable analysis demonstrated that men with elevated luteinizing hormone (LH) (OR 1.077, P = 0.001) and follicle-stimulating hormone (FSH) (OR 1.032, P = 0.002) were more likely to have hyperprolactinemia. Men with oligospermia were more likely to have hyperprolactinemia (OR 2.334, P = 0.004). On multivariable analysis, neither hormone parameters nor oligospermia were associated with elevated prolactin (P>0.05). Of the 65 men with hyperprolactinemia, 11 (17%) were diagnosed with a prolactinoma, resulting in an overall prevalence of 11 in 3101 (0.35%)., Conclusion: The overall prevalence of prolactinoma in our cohort of men undergoing fertility evaluation was 35-fold higher than the prevalence in the general male population., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To determine whether health-conscious men are more likely to be concerned about infertility and self-initiate semen analysis at a laboratory/clinic or through a direct-to-consumer at-home product without a health care provider recommendation., Methods: Cross-sectional survey conducted online via ResearchMatch.org between November 2019 and January 2020. Men age 18 and older without children (n = 634) were included for analysis. Outcomes were likelihood of self-initiating a semen analysis, prevalence of infertility concern., Results: Of the 634 participants, 186 expressed concern about infertility but only 29% were likely to discuss these concerns with a health care provider. More men would self-initiate a semen analysis using an at-home product than through a traditional laboratory/clinic (14.2% vs 10.4%, P = .04). Odds of self-initiating a traditional semen analysis were higher for men concerned about low testosterone (odds ratio [OR] 2.30, 95% confidence interval [CI] 1.12-4.74, P = .023) and infertility (OR 3.91, 95% CI 2.14-7.15, P <.001). Self-initiating an at-home semen analysis was associated with concern for low testosterone and infertility as well as middle age (age 40-59: OR 3.02, 95% CI 1.16-7.88, P = .024) and fitness tracker use (OR: 1.95, 95% CI 1.12-3.39, P = .018)., Conclusion: Many men were unlikely to discuss infertility concerns with a health care provider. Middle aged men and those who used fitness trackers were more likely to self-initiate fertility evaluation through at-home semen analysis. Concern about low serum testosterone was pervasive and strongly associated with concern for being infertile and self-initiating a semen analysis of any kind., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Extensive research has evaluated the involvement of the neuropeptide oxytocin (OT) in human social behaviors, including parent-infant relationships. Studies have investigated OT's connection to human attachment to nonhuman animals, with the majority of the literature focusing on domestic dogs ( Canis lupis familiaris ). Utilizing what is known about OT and its role in maternal-infant and human-dog bonding, we apply these frameworks to the study of human-domestic cat ( Felis catus ) interactions., Methods: We investigated changes in salivary OT levels in 30 U.S. women of reproductive age before and after two conditions: reading a book (control) and interacting with their pet cat. Participant and cat behavioral patterns during the cat interaction condition were also quantified to determine if differences in women's OT concentrations were associated with specific human and cat behaviors., Results: Our results revealed no changes in women's OT levels during the cat interaction, relative to the control condition, and pre-cat interaction OT levels. However, differences in women's OT concentrations were correlated with some human-cat interactions ( e.g. , positively with petting cat and cat approach initiation, negatively with cat agonistic behavior) but not all observed behaviors ( e.g. , use of gentle or baby voice) coded during human-cat interactions., Discussion: This study is the first to explore women's OT in response to interactions with their pet cat and has identified distinct human and cat behaviors that influence OT release in humans., Competing Interests: The authors declare there are no competing interests., (©2021 Johnson et al.)

Purpose: Priapism is a persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation and results in a prolonged and uncontrolled erection. Given its time-dependent and progressive nature, priapism is a situation that both urologists and emergency medicine practitioners must be familiar with and comfortable managing. Acute ischemic priapism, characterized by little or no cavernous blood flow and abnormal cavernous blood gases (ie, hypoxic, hypercarbic, acidotic) represents a medical emergency and may lead to cavernosal fibrosis and subsequent erectile dysfunction., Materials and Methods: A comprehensive search of the literature was performed by Emergency Care Research Institute for articles published between January 1, 1960 and May 1, 2020. Searches identified 2948 potentially relevant articles, and 2516 of these were excluded at the title or abstract level for not meeting inclusion criteria for any key question. Full texts for the remaining 432 articles were reviewed, and ultimately 137 unique articles were included in the report., Results: This Guideline was developed to inform clinicians on the proper diagnosis and surgical and non-surgical treatment of patients with acute ischemic priapism. This Guideline addresses the role of imaging, adjunctive laboratory testing, early involvement of urologists when presenting to the emergency room, discussion of conservative therapies, enhanced data for patient counseling on risks of erectile dysfunction and surgical complications, specific recommendations on intracavernosal phenylephrine with or without irrigation, the inclusion of novel surgical techniques (eg, tunneling), and early penile prosthesis placement., Conclusions: All patients with priapism should be evaluated emergently to identify the sub-type of priapism (acute ischemic versus non-ischemic) and those with an acute ischemic event should be provided early intervention. Treatment of the acute ischemic patient must be based on patient objectives, available resources, and clinician experience. As such, a single pathway for managing the condition is oversimplified and no longer appropriate. Using a diversified approach, some men may be treated with intracavernosal injections of phenylephrine alone, others with aspiration/irrigation or distal shunting, and some may undergo non-emergent placement of a penile prosthesis.

To determine the relationship between popular diets and erectile function we queried the National Health and Nutrition Examination Survey, a cross-sectional dataset, between 2001 and 2004. All men aged 18-85 who answered the prostate and dietary questionnaires were included. Diets were categorized as Mediterranean, low-fat, low-carbohydrate, or nonrestrictive. Multivariable models were created to determine the relationship between erectile function and each diet. Among 4027 men, 649 (16.1%) met criteria for a low-fat diet, 1085 (26.9%) for a Mediterranean diet, and 0 (0%) for a low-carbohydrate diet. 1999 men (49.6%) had some degree of erectile dysfunction. Men with nonrestrictive diets were more likely to endorse normal erectile function compared with those adhering to the Mediterranean or low-fat diets (both p < 0.05) on univariable analysis. Multivariable analysis controlling for age, comorbidities, activity level, and body mass index showed no differences in erectile function among men adhering to a low-fat, Mediterranean diet, or nonrestrictive diet. There was no association between specific diets and erectile function. While additional prospective research is required to corroborate these findings, these data support the notion that individualized diets should be tailored toward goals of weight loss and reduction of comorbidity., (© 2020. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To characterize the epidemiology of male factor infertility and identify which types of providers are treating infertile men in the United States., Materials and Methods: The National Ambulatory Medical Care Survey was queried between 2006 and 2016 for all ambulatory care visits. Men with a diagnosis of infertility were identified by international classification of disease coding. Comorbidities, demographic and visit information were abstracted from the patients' medical record by a combination of trained surveyors and physicians. The survey data was weighted to create nationally representative estimates, and a combination of Chi-squared and Student's t-tests were utilized to determine significance., Result(s): Among the 8.7 billion patient visits between 2006 and 2016, there were 3,422,000 male encounters with a diagnosis of male factor infertility. The most common provider type for male factor infertility encounters was urology (42.12%) followed by primary care (39.79%), gynecology (7.05%) and all other provider types (11.01%). A significant number of men seen for infertility had comorbidities such as cancer (115,000 men, 3.36%) diabetes (267,000 men, 7.81%), depression (301,000 men, 8.8%), and active tobacco use (857,000 men, 30.3%)., Conclusion: In a nationally representative sample, more than 50% of ambulatory care visits for male factor infertility were not seen by urologists. These men also had a significant number of comorbidities for a relatively young cohort, emphasizing the importance of multidisciplinary care for men with a diagnosis of infertility., (Published by Elsevier Inc.)

The relationship between testosterone and premature mortality has caused recent controversy. While previous studies have demonstrated mixed results, this is partly because of variable patient populations, different testosterone thresholds, and the use of antiquated techniques to measure serum testosterone. Using the National Health and Nutrition Examination Survey we analyzed a cohort representative of men in the USA to explore the relationship between serum testosterone and premature mortality using contemporary guidelines and testosterone measurements. We found that men with low testosterone (<300 ng/dl) were at higher risk (odds ratio 2.07, 95% confidence interval 1.30-3.32; p  < 0.01) of premature death compared to men with normal testosterone. Furthermore, men with low testosterone were also more likely to have treatable comorbid conditions that were independently predictive of premature mortality. Both testosterone and these comorbid conditions are also modulated by lifestyle modifications, rendering this an important therapeutic approach in men with either or both conditions., Patient Summary: We explored the relationship between testosterone levels and premature death in a large US population. We found that low testosterone is associated with both premature death and related disease processes such as obesity, both of which can be initially treated with diet and exercise.

Background: Direct-to-consumer (DTC) Internet-based prescription and pharmacy platforms offer electronic consultation for evaluation and pharmacologic treatment of erectile dysfunction (ED) without a physical exam or in-person visit, presenting a potentially dramatic shift in care for this condition., Aim: To characterize the extent to which DTC prescribing sites for ED generate traffic and attract individual users., Methods: Using SEMRush, a marketing software platform that provides analytics regarding website traffic, we examined online site visits to 6 major DTC prescribing websites offering ED evaluation and treatment from October 2017 through December 2019., Outcomes: We recorded trends in the number of unique visitors over time, visitor referral patterns, and the proportion of overall visitors to individual sites., Results: During the study period, the total number of unique, quarterly visitors increased by 1,688% from 655,733 in the 4th quarter (Q4) 2017 to over 11 million in Q4 2019. In 2019, there were on average 4,971,674 visits to all sites combined each month. For the 2 largest sites (Hims and Roman), visitors predominantly reached the site via direct web address (27.3%) or search engine referral (27.3%)., Clinical Implications: An increasingly large number of potential patients are utilizing DTC prescribing platforms for the diagnosis and treatment of ED, which do not require physical exams or treatment of other comorbid conditions., Strength & Limitations: Demonstrates high demand for ED DTC prescribing services using independent market research software and characterizes the number of visits for the first time. Limitations include the lack of individual demographics and lack of information regarding what proportion of unique visits lead to evaluation and treatment using the services., Conclusion: The dramatic increase in visits to DTC prescribing sites that treat ED represents a paradigm shift in ED care, and it is imperative that clinicians and researchers work to understand how patients utilize online telemedicine, the safety and efficacy of online management of ED, and the potential downstream implications of its widespread use. Wackerbarth JJ, Fantus RJ, Darves-Bornoz A, et al. Examining Online Traffic Patterns to Popular Direct-To-Consumer Websites for Evaluation and Treatment of Erectile Dysfunction. Sex Med 2021;9:100289., (Published by Elsevier Inc.)

Objectives: To evaluate the extent to which erectile dysfunction (ED) is managed by urologists versus non-urologists. We sought to characterize the epidemiology, diagnosis, and outpatient treatment of ED using a nationally representative cohort., Methods: We examined all male patient visits between 2006 and 2016 in the National Ambulatory Medical Care Survey, a survey designed to provide a nationally representative estimate of ambulatory visits in the United States. Distribution of ED diagnoses among physician specialties was determined. Demographic, clinical, and treatment characteristics of men with ED seeing urologists versus non-urologists were compared using chi-squared tests., Results: Among the 170,499 patient visits analyzed, 1.2% were associated with a diagnosis of ED, which translated into 3,409,244 weighted visits annually. Visits for ED were predominantly seen by urologists (58.0%) and family practitioners (26.2%). Men visiting non-urologists for ED were more likely to be younger than 65 (77.4% vs 52.9%, P < .05). Men seeing urologists for ED more frequently had an active cancer diagnosis (24.2% vs 2.8%, P < .05). Non-urologists more readily ordered or reordered phosphodiesterase-5 inhibitors for men with ED (66.62% vs 50.77%, P < .05). Advanced therapies such as intracavernosal injections and intra-urethral agents were almost exclusively ordered by urologists compared to non-urologists (2.72% vs 0.25%, P < .05)., Conclusion: Almost half of all ED visits were seen by non-urologist providers, who were much less likely than urologists to order advanced pharmacologic therapies. This difference in prescribing patterns presents an opportunity for interdisciplinary collaboration and education to ensure that all patients seeking treatment for ED are receiving guideline-based care., (Published by Elsevier Inc.)

Background: Exercise and weight loss have been shown to improve serum testosterone (T) in obese individuals. However, the association between low T levels and guideline-based exercise thresholds has not been determined., Objective: Using the recently updated Physical Activity Guidelines Advisory Committee (PAGAC) recommendations, we sought to investigate the relationship between recommended activity levels and the prevalence of low T levels., Materials and Methods: The2011-2016 National Health and Nutrition Examination Survey (NHANES) was used to identify men ages 18 to 80 years who answered the physical activity questionnaire and underwent serum T testing. Men were categorized based on PAGAC activity level: less than recommended, recommended and greater than recommended. Multivariable logistic regressions were used to determine the association between low T (<300 ng/dL) and activity level across body mass index (BMI) categories while adjusting for potential confounders., Results: Of the 7372 men who met the inclusion criteria, the majority (4372, 59.3%) exceeded the recommended amount of activity, whereas only 2326 (31.6%) exercised less than the recommended amount. On multivariable analysis, obese men whose activity exceeded the recommended amount were less likely to have low T (OR 0.523, 95% CI 0.409-0.669, P < .001) compared with men who did not meet the recommended activity level., Discussion and Conclusions: Using a large, nationally representative cohort, we demonstrated that obese men whose activity exceeded PAGAC recommendations had a decreased likelihood of having low T levels. Given the numerous benefits of exercise, these data provide a basis for counseling obese patients regarding the association between exercise and decreased prevalence of low T., (© 2020 American Society of Andrology and European Academy of Andrology.)

Objective: To investigate internet search results available to couples searching for a male factor infertility specialist., Design: Cross-sectional., Setting: Online search engine., Patients: The phrase "male infertility specialist " was searched in Google for 50 states and Washington D.C. The top 10 results (i.e., first page) of each search were evaluated for website content., Interventions: None., Main Outcome Measures: The first page of each search was evaluated for provider type (urology vs. obstetrics and gynecology), level of training (fellowship vs. none), male factor fertility information provided, and procedures offered. We compared search position rank (1-10) to determine the likelihood of finding an urologist versus a practitioner in obstetrics and gynecology., Results: A total of 419 results were identified; the majority were obstetrics and gynecology-related (N = 229, 54.7%). Urology-related results appeared higher than obstetrics and gynecology-related results (median, 4 vs. 5). Andrology fellowship-trained urologists were identified in 153 (36.5%) results. Among 229 obstetrics and gynecology results, 152 unique practices were identified. A small portion (N = 38, 16.6%) of these practices had a fellowship-trained urologist identified on the website. Most obstetrics and gynecology websites did not mention vasectomy reversal (N = 116, 76.3%) or varicocele repair (N = 93, 61.2%). A minority of practices offered referral to urologists for sperm extraction (N = 23, 15.1%) or offered sperm retrieval themselves (N = 23, 15.1%)., Conclusions: When searching online for a male factor infertility specialist, most results identified obstetrics and gynecology physicians. A large proportion of obstetrics and gynecology websites lacked information on male factor fertility treatments and did not offer these treatments. These data indicate the need for a more robust online presence of male reproductive urologists to optimize online access.

Introduction: Recent studies place the risk of infection following inflatable penile prosthesis (IPP) implantation at 1-2%. This risk may be underestimated due to the exclusion of high-risk patients, such as patients undergoing multiple revisions or revision following IPP infection, from data., Aim: To calculate the rate of postoperative complications for all patients undergoing IPP implantation and revision, and to determine the risk factors predictive of complications following virgin implantation and revision independently., Methods: The charts of 280 patients undergoing 331 IPP implantations performed over the last 20 years at a large academic medical center were reviewed for postoperative complications and suspected preoperative and operative risk factors., Main Outcome Measure: This included the prevalence of adverse operative outcomes including postoperative infection and device malfunction., Results: 63 (20.7%) surgeries resulted in postoperative complications: 38 (12.5%) resulting in device malfunction and 25 (8.20%) resulting in infection. Smoking (odds ratio [OR] = 4.14, P = .00) was associated with overall postoperative complications. Within subgroups, concomitant procedures (OR = 4.77, P = .03) were associated with infection for those undergoing virgin implantation, but not those undergoing revision procedures. Alternatively, diabetes mellitus (DM) (OR = 28.3, P = .02) was associated with postoperative infection for those undergoing revision procedures, but not those undergoing virgin implantation., Conclusion: The rate of postoperative infection for all patients undergoing IPP was found to be 8.20%, a higher estimate than historically recorded. To varying degrees, smoking, concomitant procedures, and DM were associated with adverse operative outcomes. Subset analyses revealed significant associations between postoperative infections and either concomitant procedures or DM in those undergoing virgin implantations or revision surgeries, respectively. Miller JA, Bennett NE. Comparing Risk Factors for Adverse Outcomes in Virgin Inflatable Penile Prosthesis Implantations and Revisions: A Retrospective Cohort Study. J Sex Med 2020;8:388-395., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To describe trends in the characteristics of urologic surgeons performing vasectomy over time., Methods: We performed a retrospective, cross-sectional study examining surgeon characteristics for case logs from the American Board of Urology between 2004 and 2013. We used generalized estimating equations with a log link and negative binomial distribution to examine demographic differences (gender, rural location, and surgeon volume) in the number of vasectomies surgeons performed over time., Results: Between 2004 and 2013, 5316 urologists had case logs collected within the 7-month certification window. The majority of these surgeons self-identified as general urologists (82.8%), and a small proportion identified as andrology and infertility specialists (1.7%). Across all years, the median number of vasectomies performed per certifying surgeon during the study period was 14 (interquartile range 6-26). The majority of vasectomies were performed by high-volume surgeons (≥ 26 vasectomies) ranging from 49.2% to 66.9% annually, whereas the proportion performed by low-volume (≤ 5 vasectomies) surgeons ranged from 3.3% to 6.6% annually. Male surgeons performed vasectomies 2.20 times more frequently than female surgeons (95% confidence interval 1.93-2.49; P <.0001) across the study period with no evidence to suggest this gap changed over time (gender-year interaction 1.01 [95% confidence interval: 0.97-1.06; p = .576])., Conclusion: While the majority of urologists performing vasectomy identify as general urologists, there appears to be a focus on vasectomy practice among a small number of high-volume surgeons. Furthermore, while the number of female surgeons performing vasectomies increased, a gender gap persists in the proportion of vasectomies performed by females., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To compare the efficacy of men's and women's cancer awareness campaigns using internet relative search volume (RSV) as a surrogate for public interest., Methods: We utilized Google Trends to determine the RSV for "breast cancer," "prostate cancer," and "testicular cancer" from 2010 to 2017. Baseline annual RSV for each cancer was calculated as the median annual RSV, exclusive of the awareness month period. RSV was then determined for each cancer-specific awareness month and compared to baseline. The primary outcome was 2-fold rise in RSV above baseline., Results: Breast Cancer Awareness Month led to a significant increase in cancer-specific RSV in October each year during the study period (mean increase 180.1%). In contrast, none of the men's cancer awareness campaigns led to a significant increase in cancer-specific RSV in any year during the study period. RSV for prostate cancer increased by 2.4% and 4.1% in September and November, respectively. RSV for testicular cancer increased by 9.3% and 6.2% in April and November, respectively., Conclusion: Men's cancer awareness campaigns did not increase cancer-specific RSV, whereas Breast Cancer Awareness Month consistently increased RSV. While additional metrics are needed to evaluate the efficacy of public health campaigns, the current data suggest the need for new approaches to generate public interest in male-specific malignancies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Recent data have suggested that short-term NSAID use induces a state of compensated hypogonadism. Our aim was to investigate the association between chronic, regular NSAID use and compensated hypogonadism in a large, nationally representative cohort, the US National Health and Nutrition Examination Survey (NHANES) database. Men 20-80 years who answered the analgesic use questionnaire and underwent hormonal testing were included. Multivariable regression was utilised to determine the relationship between NSAID use and serum testosterone (T), anti-Mullerian hormone (AMH) and T:AMH ratio. Among 3,749 men, 505 (13.5%) reported regular NSAID use and 3,244 (86.5%) did not. Regular users had lower T (440.7 ± 27.0 vs. 557.0 ± 24.9 ng/dl, p = .005) and albumin (43.8 ± 0.2 vs. 45.1 ± 0.1, p < .001) compared to nonregular users. On multivariable analysis, only active smoking was significantly associated with T, AMH and T:AMH ratio (p < .001, p = .036 and p = .005 respectively). Regular NSAID use was not associated with T, AMH or T:AMH ratio (p = .523, p = .974, and p = .872 respectively). In this nationally representative sample of US men, regular and chronic NSAID use was not associated with alterations in T or compensated hypogonadism. These data should reassure patients and clinicians regarding the safety of NSAID use with respect to the risk of alteration in the hypothalamic-pituitary-gonadal axis., (© 2020 Blackwell Verlag GmbH.)

Objective: To determine the proportion of men presenting for fertility evaluation who reported having an established primary care physician (PCP)., Design: Retrospective, observational study., Setting: Academic health center., Patients: All men presenting for initial male factor infertility consultation with a single reproductive urologist between 2002 and 2018., Interventions: Men were asked to provide the name of their PCP at the time of initial visit., Main Outcome Measures: Descriptive statistics characterized the proportion of men with a PCP at the time of evaluation and associations between PCP status and clinical characteristics., Results: Among 4,127 men presenting for initial fertility consultation, 844 (20.5%) reported having an established PCP, 480 (11.6%) reported no PCP, and 2,803 (67.9%) did not have data available. Among 1,302 men who had a prior primary care visit within our healthcare system, 414 (31.8%) had been seen within 1 year before their fertility evaluation. Men with an established PCP were slightly older than those without a PCP, with higher body mass index, and lower systolic blood pressure. Hormonal profiles were similar across groups, but men with an established PCP had a significantly higher total motile sperm count than those without a PCP, median 53 (interquartile range, 11-109) versus 35 (interquartile range, 8-98)., Conclusions: More than one third of men presenting for fertility evaluation did not have an established PCP. Reproductive urologists are uniquely positioned to facilitate the critical relationship between young men and PCPs, which should be a key component of the male fertility treatment paradigm., (© 2020 The Author(s).)

Background: The purpose of this study is to evaluate the prognostic factors for sperm retrieval and determine if Y chromosome deletion is associated with deleterious effects on spermatogenesis in non-mosaic Klinefelter patients. Whether Y chromosome deletion determines the sperm retrieval rate in non-mosaic Klinefelter patients has not yet been addressed., Methods: We retrospectively collected medical records of azoospermic patients from Sep 2009 to Dec 2018, and enrolled 66 non-mosaic 47, XXY patients who were receiving mTESE. The predictive values of patients age, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, prolactin, estradiol and Y chromosome deletion were assessed for successful sperm recovery., Results: Testicular sperm recovery was successful in 24 (36.4%) of 66 men. The mean age (36.0 vs. 36.6 years), and levels of FSH (30.0 vs 36.9 IU/L), LH (17.7 vs 21.9 IU/L), testosterone (2.4 vs. 2.1 ng/ml), prolactin (9.1 vs. 8.8 ng/ml), and estradiol (19.4 vs. 22.3 pg/ml) did not show any significant difference when comparing patients with and without successful sperm retrieval. Partial deletion of azoospermic factor c (AZFc) was noted in 5 (20.8%) of 24 patients with successful sperm retrieval, including three b2/b3 and two gr/gr deletion cases, whereas 4 (9.5%) of 42 patients with unsuccessful sperm retrieval were noted to have AZFc partial deletion (one b2/b3, one sY1206 and two gr/gr deletion), though the difference was not statistically significant (p = 0.27)., Conclusion: According to present results, age and AZFc partial deletion status should not be a deterrent for azoospermic males with non-mosaic Klinefelter syndrome to undergo mTESE.