Faculty Bibliography

BACKGROUND:Transcervical arterial ligation has been studied as a useful procedure to prevent bleeding events after transoral robotic surgery (TORS). METHODS:A systematic review of English-language literature on arterial ligation in TORS from 2005 to 2019 was conducted using Cochrane, PubMed, Web of Science (WoS), and ScienceDirect databases. Studies evaluating ligation and rates of postoperative hemorrhage were included. Meta-analysis of included studies was performed to assess impact of ligation on postoperative hemorrhage. RESULTS:Five studies with 2008 patients were included. History of radiation (odds ratio [OR] = 2.26, P = .02) and advanced tumor stage (OR = 1.93, P = .02) were found to predispose patients to postoperative hemorrhage. Arterial ligation was protective against severe hemorrhage in the mixed primary surgical modality cohort (OR = 0.33, P = .03) and in the TORS-only subgroup (OR = 0.21, P = .02), but did not significantly impact overall odds of postoperative hemorrhage. CONCLUSION:Transcervical arterial ligation offers protection against major/severe postoperative hemorrhage in patients undergoing TORS. LEVEL OF EVIDENCE:II.

Despite the success of immune checkpoint blockade therapy, few strategies sufficiently overcome immunosuppression within the tumor microenvironment (TME). Targeting regulatory T cells (T_regs) is challenging, because perturbing intratumoral T_reg function must be specific enough to avoid systemic inflammatory side effects. Thus, no T_reg-targeted agents have proven both safe and efficacious in patients with cancer. Neuropilin-1 (NRP1) is recognized for its role in supporting intratumoral T_reg function while being dispensable for peripheral homeostasis. Nonetheless, little is known about the biology of human NRP1⁺ T_regs and the signals that regulate NRP1 expression. Here, we report that NRP1 is preferentially expressed on intratumoral T_regs across six distinct cancer types compared to healthy donor peripheral blood [peripheral blood lymphocyte (PBL)] and site-matched, noncancer tissue. Furthermore, NRP1⁺ T_reg prevalence is associated with reduced progression-free survival in head and neck cancer. Human NRP1⁺ T_regs have broad activation programs and elevated suppressive function. Unlike mouse T_regs, we demonstrate that NRP1 identifies a transient activation state of human T_regs driven by continuous T cell receptor (TCR) signaling through the mitogen-activated protein kinase pathway and interleukin-2 exposure. The prevalence of NRP1⁺ T_regs in patient PBL correlates with the intratumoral abundance of NRP1⁺ T_regs and may indicate higher disease burden. These findings support further clinical evaluation of NRP1 as a suitable therapeutic target to enhance antitumor immunity by inhibiting T_reg function in the TME.

INTRODUCTION/BACKGROUND:YouTube is an unregulated platform that patients are using to learn about treatment options. AIM/OBJECTIVE:To assess the reliability of YouTube videos (YTVs) related to male hypogonadism and testosterone therapy. METHODS:Searching on YouTube by relevance and view count, we analyzed the top 10 videos (80 videos total) for the following search terms: low testosterone, testosterone replacement therapy, AndroGel, and hypogonadism. MAIN OUTCOME MEASURE/METHODS:We recorded the number of views for each video, evaluated videos using the DISCERN score (DS) criterion, and compared the DS for videos including board-certified physicians and videos without. A second comparison was made between videos with board-certified physicians in urology, endocrinology, other MD, and those without any physician. RESULTS:The YTVs analyzed received a total of 38,549,090 views, a median of 25,201 and 17.30 views/day. Videos that featured physicians had significantly fewer views/day than videos that did not (39.48 CI 9,72 vs 1,731 CI 330, 3,132; P = .019). Most YTVs studied were unreliable. The median DS across all videos was 2. However, most videos created by physicians were found to be reliable with a median DS of 4. In addition, YTVs that did not feature a physician were found to be significantly less reliable than videos that featured a physician (3.22 CI 3.06, 4.09 vs 1.87 CI 1.56, 2.18; P < .001). There was no significant difference in the reliability or viewership of YTVs stratified by physician type. CONCLUSION/CONCLUSIONS:Most YTVs related to male hypogonadism/testosterone therapy were unreliable, but there are reliable YTVs available. Reliable videos usually feature a physician and receive fewer views than unreliable YTVs. Physicians and academic societies should work to provide verified videos to provide patients with reliable information about male hypogonadism and testosterone therapy. CJ Warren, J Wisener, B Ward, et al. YouTube as a Patient Education Resource for Male Hypogonadism and Testosterone Therapy. Sex Med 2021;9:100324.

Epilepsy is a common neurological disorder affecting over 70 million people worldwide, with a high rate of pharmaco-resistance, diverse comorbidities including progressive cognitive and behavioural disorders, and increased mortality from direct (e.g. sudden unexpected death in epilepsy, accidents, drowning) or indirect effects of seizures and therapies. Extensive research with animal models and human studies provides limited insights into the mechanisms underlying seizures and epileptogenesis, and these have not translated into significant reductions in pharmaco-resistance, morbidities or mortality. To help define changes in molecular signalling networks associated with seizures in epilepsy with a broad range of aetiologies, we examined the proteome of brain samples from epilepsy and control cases. Label-free quantitative mass spectrometry was performed on the hippocampal cornu ammonis 1-3 region (CA1-3), frontal cortex and dentate gyrus microdissected from epilepsy and control cases (n = 14/group). Epilepsy cases had significant differences in the expression of 777 proteins in the hippocampal CA1 - 3 region, 296 proteins in the frontal cortex and 49 proteins in the dentate gyrus in comparison to control cases. Network analysis showed that proteins involved in protein synthesis, mitochondrial function, G-protein signalling and synaptic plasticity were particularly altered in epilepsy. While protein differences were most pronounced in the hippocampus, similar changes were observed in other brain regions indicating broad proteomic abnormalities in epilepsy. Among the most significantly altered proteins, G-protein subunit beta 1 (GNB1) was one of the most significantly decreased proteins in epilepsy in all regions studied, highlighting the importance of G-protein subunit signalling and G-protein-coupled receptors in epilepsy. Our results provide insights into common molecular mechanisms underlying epilepsy across various aetiologies, which may allow for novel targeted therapeutic strategies.

BACKGROUND Invasive mucormycosis is a rare, life-threatening infection that requires urgent medical management. Here we describe a patient who developed invasive mucormycosis after receiving only a short course of dexamethasone. The purpose is to highlight this atypical presentation of a rare disease. CASE REPORT A 74-year-old woman with a medical history of diabetes mellitus (DM), hypertension, hyperlipidemia, and small cell lung cancer with metastasis to the brain presented to the Emergency Department with altered mental status and a hyperosmolar hyperglycemic state. Three weeks before, she had been diagnosed with DM (hemoglobin A1c [HbA1c] 6.5%) and was started on dexamethasone to treat cerebral edema. On admission, her HbA1c was 10.8%, although she had received only a short course of dexamethasone. Her physical exam was concerning for left eyelid swelling and ophthalmoplegia. Computed tomography of the head and neck revealed signs of left ocular proptosis and invasive rhinomaxillary fungal disease. The patient underwent urgent surgical debridement; subsequent magnetic resonance imaging revealed extensive fungal disease extending into her left inferior frontal lobe. A surgical pathology report was positive for Rhizopus oryzae and Stenotrophomonas maltophilia. Her blood cultures were positive for methicillin-susceptible Staphylococcus aureus. She was treated with antibiotics and amphotericin B. Her clinical course was complicated by hypokalemia. She eventually recovered and was discharged from the hospital. CONCLUSIONS This case highlights an atypical presentation of mucormycosis. Clinicians should remain vigilant for this rare complication of dexamethasone use even when the therapy is given for a short time.

OBJECTIVES:Sinonasal mucosal melanoma (SNMM) is an aggressive cancer usually managed with surgical resection. This study evaluates the impact of treatment modality and positive surgical margin (PSM) on survival following resection of SNMM. STUDY DESIGN:Retrospective study of a national cancer registry. METHODS:The National Cancer Database was queried for cases of SNMM from 2010 to 2015. Data regarding patient demographics, tumor staging, and treatment modality were obtained. Survival rates were compared by margin status: PSM, negative (NSM), and no operation (0SM) using Kaplan-Meier analysis and log rank test. RESULTS:A total of 446 patients met inclusion criteria. Most cases were elderly (>66 years-old) (67.3%), female (54.3%), and white (89.5%). Cases of SNMM most commonly involved the nasal cavity (81.6%), were Stage 3 (60.0%), and underwent surgical resection at an academic center (65.0%). NSM and PSM were present in 59.0% and 26.9% of cases, respectively, while 14.1% of cases did not undergo surgical resection (0SM). Factors predictive of PSM included resection at a community hospital (OR 2.47) and Stage 4 disease (OR 2.07). The 2-year survival rates were 72.1% (95% CI 69.4-75.4%), 36.3% (95% CI 22.0-48.9), and 16.0% (95% CI 8.2-25.4%) for NSM, PSM and 0SM, respectively. Survival was statistically significant between NSM and PSM (Log rank <0.001) but not between 0SM and PSM (Log rank = 0.062). CONCLUSION:Our study emphasizes the need for NSM for SNMM as PSM did not demonstrate any significant improvement in survival when compared to 0SM. Our findings suggest that cases of SNMM are best managed at academic centers. LEVEL OF EVIDENCE:4 Laryngoscope, 131:2429-2435, 2021.