Changing Trends in Management Following Artificial Urinary Sphincter Surgery for Male Stress Urinary Incontinence: An Analysis of the National Surgical Quality Improvement Program Database.

OBJECTIVE: To characterize the safety and practice patterns of artificial urinary sphincter (AUS) placement on a population level. Increasingly AUS implantation has shifted to be an outpatient surgery; however, there is a lack of large-scale research evaluating factors associated with early (≤ 24 hours) versus late (>24 hours) discharges and complications in men following AUS placement. We utilized the National Surgical Quality Improvement Program (NSQIP) database to identify and compare factors and outcomes associated with each approach. METHODS: NSQIP database was queried for men undergoing AUS placement between 2007 and 2016. Patients were classified as either early discharge (ED ≤ 24 hours) and late discharge (LD > 24 hours). Baseline demographics, operating time, and complications were compared between the 2 groups. Multivariate logistic regression evaluated factors associated with discharge timing and 30-day complications. RESULTS: A total of 1176 patients were identified and were classified as ED in 232 and LD in 944 patients. Operative time was shorter in ED (83 minutes) compared to LD (95 minutes, P < .001). Hypertension was more prevalent among LD patients (60.3% vs 69.1% for ED and LD respectively, P < .001). The 30-day complication rate was similar in both groups (ED: 4.3% vs LD: 3.4%, P = .498). Multivariable analysis revealed that surgery after 2012 was associated with ED (OR = 3.66, P < .001). CONCLUSION: At the national level, there are no differences in postoperative morbidity between early and late discharges. There is a trend toward more ED, specifically after 2012. A prospective study on the feasibility and safety of outpatient AUS is needed.

The Conception and Evaluation of Sexual Health Literature.

INTRODUCTION: Understanding the appropriate evaluation and development methods for studying the literature as it pertains to sexual health is important for those practicing within the subspecialty. AIM: To further understand the methodology that is necessary to evaluate and design optimal studies in sexual health. METHODS: A PubMed search was performed using the terms urologic study design, urologic validated questionnaires, clinical trials, and study bias. Articles with current and relevant topics in sexual health were selected for evaluation. MAIN OUTCOME MEASURE: Summary of the current state of sexual medicine literature with insights into the evaluation and development of this literature. RESULTS: Most of the urologic and sexual medicine literature consists of retrospective studies that have resulted in low levels of evidence. Case series, case-control studies, cohort studies, and experimental studies are designs commonly used in sexual health. There are numerous types of bias that decrease the validity of the results within the literature. There are multiple validated questionnaires that can decrease bias when collecting data. These instruments are preferred over non-validated questionnaires and can help discern whether an intervention improves a patient's quality of life. The quality of the literature varies and often reflects the incidence of the condition being studied. CONCLUSION: Those caring for patients with sexual dysfunction need to recognize the quality of the literature they read and understand the means of developing the highest quality studies, recommendations, and published literature. DeLay KJ, Voznesensky I, Hellstrom WJG. The Conception and Evaluation of Sexual Health Literature. Sex Med Rev 2017;5:135-145.

Advances in pharmacotherapy for erectile dysfunction and associated cardiac impact.

INTRODUCTION: Cardiovascular disease (CVD) and erectile dysfunction (ED) are two disease processes that affect millions of men. CVD and ED are increasingly recognized as sharing a common pathophysiologic origin. As the nature of this relationship continues to be elucidated, there is growing interest in developing a therapy to effectively target both processes. While researchers have largely focused on phosphodiesterase-5 inhibitors (PDE5Is), the established first-line therapy for ED, newer ED drugs, designed based on better understanding of the physiology of erection, may also show promise. Areas covered: This paper will review the relationship between ED and CVD, as well as the currently available and investigational pharmacologic treatments for ED. The particular focus will be on the role that these therapies play in managing CVD. Expert opinion: PDE5Is, along with the newer ED therapies, are promising candidates for managing ED and concurrently providing cardioprotection. Despite some in vitro success with PDE5Is, maxi-K channel activators, and guanylyl cyclase (GC) stimulators, in vivo studies have either been lacking, or shown conflicting results. More well designed clinical studies are needed in order to characterize an ED pharmacotherapy that offers proven cardioprotection.

An HIV-1 replication pathway utilizing reverse transcription products that fail to integrate.

Integration is a central event in the replication of retroviruses, yet ≥ 90% of HIV-1 reverse transcripts fail to integrate, resulting in accumulation of unintegrated viral DNA in cells. However, understanding what role, if any, unintegrated viral DNA plays in the natural history of HIV-1 has remained elusive. Unintegrated HIV-1 DNA is reported to possess a limited capacity for gene expression restricted to early gene products and is considered a replicative dead end. Although the majority of peripheral blood CD4(+) T cells are refractory to infection, nonactivated CD4 T cells present in lymphoid and mucosal tissues are major targets for infection. Treatment with cytokine interleukin-2 (IL-2), IL-4, IL-7, or IL-15 renders CD4(+) T cells permissive to HIV-1 infection in the absence of cell activation and proliferation and provides a useful model for infection of resting CD4(+) T cells. We found that infection of cytokine-treated resting CD4(+) T cells in the presence of raltegravir or with integrase active-site mutant HIV-1 yielded de novo virus production following subsequent T cell activation. Infection with integration-competent HIV-1 naturally generated a population of cells generating virus from unintegrated DNA. Latent infection persisted for several weeks and could be activated to virus production by a combination of a histone deacetylase inhibitor and a protein kinase C activator or by T cell activation. HIV-1 Vpr was essential for unintegrated HIV-1 gene expression and de novo virus production in this system. Bypassing integration by this mechanism may allow the preservation of genetic information that otherwise would be lost.

Relative contribution of free-virus and synaptic transmission to the spread of HIV-1 through target cell populations.

Human immunodeficiency virus can spread through target cells by transmission of cell-free virus or directly from cell-to-cell via formation of virological synapses. Although cell-to-cell transmission has been described as much more efficient than cell-free infection, the relative contribution of the two transmission pathways to virus growth during multiple rounds of replication remains poorly defined. Here, we fit a mathematical model to previously published and newly generated in vitro data, and determine that free-virus and synaptic transmission contribute approximately equally to the growth of the virus population.

New kinase regulation mechanism found in HipBA: a bacterial persistence switch.

Bacterial persistence is the ability of individual cells to randomly enter a period of dormancy during which the cells are protected against antibiotics. In Escherichia coli, persistence is regulated by the activity of a protein kinase HipA and its DNA-binding partner HipB, which is a strong inhibitor of both HipA activity and hip operon transcription. The crystal structure of the HipBA complex was solved by application of the SAD technique to a mercury derivative. In this article, the fortuitous and interesting effect of mercury soaks on the native HipBA crystals is discussed as well as the intriguing tryptophan-binding pocket found on the HipA surface. A HipA-regulation model is also proposed that is consistent with the available structural and biochemical data.