Direct-To-Consumer Internet Prescription Platforms Overlook Crucial Pathology Found During Traditional Office Evaluation of Young Men With Erectile Dysfunction.

OBJECTIVE: To determine comorbidities in young men with erectile dysfunction (ED) who are increasingly targeted by direct-to-consumer (DTC) internet platforms that sell phosphodiesterase-5 (PDE-5) inhibitors without comprehensive clinical evaluation; and, further, to characterize the portrayal of DTC platforms by popular news media. METHODS: We retrospectively reviewed all men age ≤40 evaluated for ED at an andrology clinic during January 2016-March 2019 to obtain demographics, exam and lab findings, and treatments. Five news sources were analyzed during the study period to characterize whether articles about DTC platforms were positive, critical, or balanced/neutral. RESULTS: We identified 388 patients, with age 29.5 ± 5.0 years, 15% rate of obesity, 20% prediabetes or diabetes, 54% dyslipidemia, and 20% hypogonadism. Serum lab findings associated with subfertility were found in 11%. Semen analysis was conducted in 64 men, of whom 40% were abnormal. Varicoceles were found in 35%. PDE-5 inhibitor was prescribed to 328 men (88%). Off-label empiric therapies included clomiphene (32.9%) or aromatase inhibitor (12.1%). Testosterone replacement was initiated in 9.7%. Analysis of news coverage revealed 18 articles, of which 61% portrayed DTC platforms exclusively in a positive light. CONCLUSION: Office consultation identified young men with significant comorbidities that would be missed by DTC platforms, which employ only questionnaires for health screening. DTC platforms present themselves as medical authorities without following AUA Guidelines, yet garner mostly positive press coverage. Patients engaging these platforms may falsely believe they are receiving adequate medical assessment. Urologists may do well to incorporate telemedicine to enfranchise young men with evidence-based evaluation.

Decisional Conflict and Knowledge Among Patients With Varicocele Seeking Treatment for Infertility.

OBJECTIVE: To study disease-specific knowledge and decisional quality in men with varicocele being counseled for infertility. MATERIALS AND METHODS: An instrument designed to measure decisional quality by evaluating disease-specific knowledge, decisional conflict, and the impression that shared decision-making was administered to 92 men identified to have a varicocele seeking their initial infertility consultation. Mean scores on disease-specific knowledge questionnaire, prevalence of decisional conflict, and impact of consultation on preferred infertility treatment were analyzed. RESULTS: Fifty-five percent of patients were found to have decisional conflict. Compared to those with decisional conflict, men without decisional conflict scored higher on the infertility knowledge assessment (63% vs 53% correct) and were more likely to feel that they discussed treatment options with their physician in detail (98% vs 82%) (all P <0.01). Prior to consultation, 28% of all patients preferred assisted reproductive technologies and 2% preferred varicocelectomy as the primary treatment for infertility. Following consultation, 12% and 17% preferred assisted reproductive technologies and varicocelectomy, respectively. The increase in preference for varicocelectomy was greater in men without decisional conflict (5%-31%) than those with conflict (0%-8%) (P = 0.03). CONCLUSION: Infertile men with varicocele have limited knowledge of their disease and high rates of decisional conflict. Before consultation, men with varicoceles showed preference for assisted reproductive technology over varicocele surgery; this trend reversed after consultation. Men with decisional conflict were less likely to prefer varicocelectomy, even after consultation.

A modified technique for intralesional injection of collagenase Clostridium histolyticum for Peyronie's disease results in reduced procedural morbidity using a standardized hematoma classification rubric.

PURPOSE: Early clinical trials of injectable collagenase Clostridium histolyticum (CCh) for Peyronie's disease (PD) demonstrated safety and efficacy. Since then, modified injection protocols have been proposed. Adverse events-such as bruising, swelling, hematoma, and corporal rupture-exceed 50% in many studies, but lack of standardization of hematoma severity limits conclusions about the relative safety of protocols. We propose a modification of the standard injection technique that aims to decrease the rates of adverse events. We further describe a hematoma classification rubric that may standardize safety assessment. METHODS: A modified injection procedure, termed the "fan" technique, was employed in the treatment of PD. All men receiving CCh from January 2016 through January 2019 at a single institution were included in an institutional review board (IRB) approved database. Treatment outcomes and adverse events were retrospectively assessed. A three-tiered hematoma classification rubric was devised to standardize reporting of hematoma, which was defined as concurrent bruising and swelling at the site of injection without loss of erection. RESULTS: Using the fan technique, 152 patients received 1323 injections. Eight hematomas (5.3% of all patients, 0.6% of all injections) were observed. The number of grade I, grade II, and grade III hematomas were 3, 2, and 3, respectively. Bruising or swelling not meeting the definition of hematoma was seen in 54.6% and 27.0% of patients, respectively. There were zero corporal ruptures. CONCLUSION: A modified injection technique results in reduced procedural morbidity. A hematoma classification system provides clarity and standardization to the assessment of safety in PD treatment. Further clinical studies with control arms are required to verify these findings.

Safety of Collagenase Clostridium histolyticum Injection Therapy for Peyronie Disease in Patients Continuing Antiplatelet or Anticoagulant Therapy.

INTRODUCTION: The initial clinical trials for intralesional collagenase Clostridium histolyticum (CCh) injection therapy for Peyronie disease (PD) excluded men on antiplatelet or anticoagulant medications except those on low-dose aspirin. Men with PD who take such medications present a challenging clinical scenario because of a lack of evidence regarding the safety of CCh while on these drugs. AIM: To evaluate safety outcomes among patients continuing anticoagulant and antiplatelet therapy during ongoing intralesional CCh injection treatment for PD. METHODS: An institutional review board approved a database of 187 patients treated with CCh at an academic men's health practice from January 2016 through April 2019 was reviewed. Men on antiplatelet/anticoagulant medications were not instructed to stop these agents. Data on patient demographics, comorbidities, CCh injection details, use or nonuse of antiplatelet/anticoagulant medications, and adverse events were extracted from the electronic medical record. Rates of hematoma formation, bruising, swelling, and corporal rupture were determined. Univariate statistical analysis compared clinical data and adverse events between men on or off antiplatelet/anticoagulant medications. MAIN OUTCOME MEASURE: Statistical comparison of adverse events in those taking or not taking antiplatelet or anticoagulant medications while undergoing intralesional CCh injection therapy for PD. RESULTS: Of 187 men undergoing CCh treatment, 33 (17.6%) were on concomitant antiplatelet or anticoagulant therapy. Aspirin 81 mg alone was the most common pharmacologic agent (58% of men on antiplatelet/anticoagulants); medications also included other antiplatelet drugs, warfarin, and novel oral anticoagulants (NOACs). Men taking blood thinners during intralesional CCh injection therapy experienced no statistical difference in rates of bruising, swelling, or hematoma formation compared with men not on antiplatelet/anticoagulants. No corporal ruptures were observed in either group. Men on antiplatelet or anticoagulant therapy were more likely to be older (64 vs 58 years old, P = 0.005), have hypertension (P = 0.025), and have hyperlipidemia (0.009). CLINICAL IMPLICATIONS: Intralesional CCh injection therapy may be offered to men on antiplatelet/anticoagulant medications without increased risk of adverse events. STRENGTH & LIMITATIONS: This study evaluated the experience of a single surgeon, with a systematic evaluation of adverse events captured in a robust electronic medical record. The retrospective nature of this study limits conclusions but builds upon work performed in the initial clinical trials for CCh. CONCLUSION: Our findings suggest that antiplatelet and anticoagulant medications do not increase the risk of adverse events during intralesional CCh injection therapy for PD. Amighi A, Regets KV, Nork JJ, et al. Safety of Collagenase Clostridium histolyticum Injection Therapy for Peyronie Disease in Patients Continuing Antiplatelet or Anticoagulant Therapy. J Sex Med 2020;17:353-356.

Discontinuation from Collagenase Clostridium histolyticum Therapy for Peyronie's Disease: Review and Single-Center Cohort Analysis.

INTRODUCTION: Intralesional injection therapy with collagenase Clostridium histolyticum (CCh) is an effective treatment option for Peyronie's disease (PD), but it carries risks, costs, and the need for multiple visits, which may cause patients to discontinue therapy prematurely. AIMS: To identify and summarize the current literature on CCh discontinuation and present our experience with CCh discontinuation. METHODS: We performed a PubMed review of existing literature on discontinuation from CCh therapy and retrospectively analyzed our prospectively maintained Institutional Review Board-approved CCh database for January 2016-December 2018. Demographic information, clinical outcomes, and communication logs were collected. Reasons for discontinuation of therapy were assessed. A logistic regression to identify factors influencing dropout was performed. MAIN OUTCOME MEASURES: Documentation of discontinuation statistics in published literature, and rates of and reasons for discontinuation in a single-institution cohort. RESULTS: Our literature review identified 15 studies with specified cohort sizes. Of these, 10 specifically quantified discontinuation rates, which ranged from 13% to 56%. Combined, these studies show a 20% dropout rate. Dissatisfaction with therapy was the most common reason for dropout. In our cohort, 100 men completed a course of 8 CCh injections. Twelve men (10.7%) discontinued therapy, including 4 due to relocation, 3 due to cost, 1 due to a hematoma, 1 due to early satisfaction, 2 due to no perceived improvement, and 1 due to a demanding work schedule. Hematoma formation was a predictor of dropout in our cohort (odds ratio 8.74; P = .037). CONCLUSION: Additional focus must be placed on quantifying and evaluating CCh discontinuation. Our findings show that a majority of men complete a full course of 8 injections; most of the few men who dropped out of therapy did so due to relocation. Counseling to reduce CCh discontinuation should focus on initial sexual function, adverse events, and expectations. Amighi A, Eleswarapu SV, Mendhiratta N, et al. Discontinuation from Collagenase Clostridium histolyticum Therapy for Peyronie's Disease: Review and Single-Center Cohort Analysis. Sex Med Rev 2019;7:690-698.

Enhanced-acceptor fluorescence-based single cell ATP biosensor monitors ATP in heterogeneous cancer populations in real time.

Current methods to monitor cellular ATP do not provide spatial or temporal localization of ATP in single cells in real time or they display imperfect specificity to ATP. Here, we have developed a single cell, Enhanced Acceptor Fluorescence (EAF)-based ATP biosensor to visualize ATP in real time. This biosensor utilizes a modified mimic of the ε-subunits of the Bacillus subtilis F(0)F(1) synthase and is coupled to the EAF fluorophores pairs, GFP and YFP. The sensor was then used to monitor ATP in a heterogeneous glioblastoma multiform cancer cell population. We anticipate that this innovative technology and our better understanding of the ATP machinery will have substantial influence on future translational studies.

Fluorescence resonance energy transfer (FRET)-based biosensors: visualizing cellular dynamics and bioenergetics.

Förster (or fluorescence) resonance energy transfer (FRET) is a process involving the radiation-less transfer of energy from a "donor" fluorophore to an "acceptor" fluorophore. FRET technology enables the quantitative analysis of molecular dynamics in biophysics and in molecular biology, such as the monitoring of protein-protein interactions, protein-DNA interactions, and protein conformational changes. FRET-based biosensors have been utilized to monitor cellular dynamics not only in heterogeneous cellular populations, but also at the single-cell level in real time. Lately, applications of FRET-based biosensors range from basic biological to biomedical disciplines. Despite the diverse applications of FRET, FRET-based sensors still face many challenges. There is an increasing need for higher fluorescence resolution and improved specificity of FRET biosensors. Additionally, as more FRET-based technologies extend to medical diagnostics, the affordability of FRET reagents becomes a significant concern. Here, we will review current advances and limitations of FRET-based biosensor technology and discuss future FRET applications.

ENTPD5-mediated modulation of ATP results in altered metabolism and decreased survival in gliomablastoma multiforme.

Gliomablastoma multiforme (GBM) is the most aggressive of brain cancers in humans. Response to current therapies remains extremely poor, with dismal survival statistics. Recently, the endoplasmic reticulum UDPase, ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5), was identified as a key component in the Akt/phosphatidylinositol 3-kinase/phosphatase and tensin homolog regulatory loop, capable of synergizing aerobic glycolysis and cancer cell proliferation in vitro. Utilizing a novel enhanced acceptor fluorescence-based single-cell adenosine 5'-triphosphate (ATP) biosensor, we analyzed ENTPD5-mediated modulation of cytosolic ATP. Here, ENTPD5-dependent modulation of cellular ATP in GBM results in altered metabolic kinetics in vitro, increasing the catabolic efficiencies of aerobic glycolysis and fatty acid oxidation. Additionally, an upregulation of ENTPD5 in both GBM mouse xenografts and in GBM patient tumors was identified, resulting in dramatically reduced survival. Therefore, these results not only provide new tools to monitor ATP flux and cellular metabolism kinetics but also identified a novel therapeutic target for GBM.