High-contrast visualization of human skin cancers with combined reflectance confocal and moxifloxacin-based two-photon microscopy: An ex vivo study.

BACKGROUND AND OBJECTIVES: Precise determination of cancer margin during skin cancer surgery is crucial for complete resection and further clinical prognosis. Although reflection confocal microscopy (RCM) has been used for perioperative guiding, its reflection contrast has limitations in detecting cancer cells in the dermis. We previously developed combined reflection confocal (RC) and moxifloxacin-based two-photon (MB-TP) microscopy for sensitive cancer detection by using multiple contrast mechanisms. In this study, the performance of combined microscopy was characterized in various skin cancer specimens and compared with standard methods. MATERIALS AND METHODS: Seven human skin specimens in total including two normal ones, three basal cell carcinomas (BCCs), and two squamous cell carcinomas (SCCs) were collected and imaged in fresh condition. Moxifloxacin ophthalmic solution was topically instilled for cell labeling for 3-5 minutes, then mosaic imaging with the combined microscopy was conducted. The imaged specimens were imaged again after exogenous nuclear labeling for comparison and then processed for standard hematoxylin and eosin histology. RESULTS: Combined RC and MB-TP microscopy visualized both cell and extracellular matrix structures of the skin specimens with multiple contrasts of reflection, moxifloxacin fluorescence, autofluorescence, and second harmonic generation. It distinguished normal cell structures in the skin dermis such as hair follicles, sebaceous and eccrine glands from BCC nests, and SCCs based on cell organization. Normal cell structures had organized cell arrangements for their functions, while cancer cell structures had dense and disorganized cell arrangements. Cellular features found by combined microscopy images were confirmed by both TP microscopy with nuclear labeling and histological examination. CONCLUSIONS: The imaging results showed the potential of combined microscopy for sensitive cancer detection and in vivo guiding of skin cancer surgery.

Long-acting GLP-1RAs: An overview of efficacy, safety, and their role in type 2 diabetes management.

Over recent decades, an improved understanding of the pathophysiology of type 2 diabetes mellitus (T2DM) and glucose regulation has led to innovative research and new treatment paradigms. The discovery of the gut peptide glucagon-like peptide-1 (GLP-1) and its role in glucose regulation paved the way for the class of GLP-1 receptor agonist compounds, or GLP-1RAs. The long-acting GLP-1RAs (dulaglutide, exenatide extended-release, liraglutide, semaglutide [injectable and oral]) are classified as such based on a minimum 24-hour duration of clinically relevant effects after administration. In phase 3 clinical trial programs of long-acting GLP-1RAs, A1C typically was reduced in the range of 1% to 1.5%, with reductions close to 2% in some studies. GLP-1RAs when used alone (without sulfonylureas or insulin) have a low risk of hypoglycemia because, like endogenous GLP-1, their insulinotropic effects are glucose-dependent. In addition to local actions in the gastrointestinal (GI) tract, GLP-1RAs stimulate receptors in the central nervous system to increase satiety, resulting in weight loss. All long-acting GLP-1RAs have, at minimum, been shown to be safe and not increase cardiovascular (CV) risk and most (liraglutide, semaglutide injectable, dulaglutide, albiglutide) have been shown in CV outcomes trials (CVOTs) to significantly reduce the risk of major cardiac adverse events. The class has good tolerability overall, with generally transient GI adverse events being most common. The weekly injectable agents offer scheduling convenience and may promote treatment adherence. One long-acting GLP-1RA is available as an oral daily tablet, which may be preferable for some patients and providers.

Long-acting GLP-1RAs: An overview of efficacy, safety, and their role in type 2 diabetes management.

Over recent decades, an improved understanding of the pathophysiology of type 2 diabetes mellitus (T2DM) and glucose regulation has led to innovative research and new treatment paradigms. The discovery of the gut peptide glucagon-like peptide-1 (GLP-1) and its role in glucose regulation paved the way for the class of GLP-1 receptor agonist compounds, or GLP-1RAs. The long-acting GLP-1RAs (dulaglutide, exenatide extended-release, liraglutide, semaglutide [injectable and oral]) are classified as such based on a minimum 24-hour duration of clinically relevant effects after administration. In phase 3 clinical trial programs of long-acting GLP-1RAs, A1C typically was reduced in the range of 1% to 1.5%, with reductions close to 2% in some studies. GLP-1RAs when used alone (without sulfonylureas or insulin) have a low risk of hypoglycemia because, like endogenous GLP-1, their insulinotropic effects are glucose-dependent. In addition to local actions in the gastrointestinal (GI) tract, GLP-1RAs stimulate receptors in the central nervous system to increase satiety, resulting in weight loss. All long-acting GLP-1RAs have, at minimum, been shown to be safe and not increase cardiovascular (CV) risk and most (liraglutide, semaglutide injectable, dulaglutide, albiglutide) have been shown in CV outcomes trials (CVOTs) to significantly reduce the risk of major cardiac adverse events. The class has good tolerability overall, with generally transient GI adverse events being most common. The weekly injectable agents offer scheduling convenience and may promote treatment adherence. One long-acting GLP-1RA is available as an oral daily tablet, which may be preferable for some patients and providers.