Search

Summary Objective Weight management pharmacotherapies can improve metabolic diseases through weight‐dependent and weight‐independent effects. Lorcaserin is a selective 5‐hydroxytryptamine 2C receptor agonist. The objective of this analysis is to quantify the relative contribution of weight loss to the treatment effects of lorcaserin 10 mg twice a day on key metabolic parameters. Methods This retrospective analysis evaluated 6,897 patients with overweight or obesity (with or without diabetes mellitus) across three randomized, placebo‐controlled, double‐blind, 52‐week clinical trials that evaluated lorcaserin 10 mg twice daily (BID; NCT00395135, NCT00603902, and NCT00603291); 509 patients from only one of the studies had type 2 diabetes mellitus. A mediation analysis was applied to help rank the relative contribution of weight loss to metabolic study outcomes. Results According to this mediation analysis, lorcaserin 10 mg BID improved a spectrum of adiposopathic metabolic abnormalities with varying contributions attributable to weight loss. Improvements in waist circumference and blood pressure were almost exclusively attributable to weight loss. Less than 50% of the improvement in glucose parameters (fasting blood glucose and haemoglobin A1c) were attributable to weight loss. Conclusions Across Phase III clinical trials, lorcaserin 10 mg BID improved multiple cardiometabolic parameters through both weight‐loss dependent and independent mechanisms.

The authors present the clinical, histopathologic, and immunomorphologic data of 13 intracranial gangliogliomas. Preoperative computed tomography scans showed a commonly cystic tumor of variable density. Six tumors were completely excised and seven were subtotally resected. After a mean follow-up of 4.5 +/- 2.6 years, 11 patients are asymptomatic or only slightly incapacitated. All tumors were examined with a panel of neuronal and neuroendocrine markers. Immunoreactivity (IR) to anti-neurofilament polypeptide (clone 2F11) was observed in neuronal processes in ten cases and in neuronal perikarya in five. With anti-synaptophysin (clone SY38), IR was present along the lining of ganglion cell perikarya and processes in 11 tumors whereas staining of the perinuclear cytoplasm was prominent in two. IR to anti-chromogranin A (clone LK2H10) was observed within the neuronal perikarya in eight cases. Only one ganglioglioma of the brain stem showed IR for tyrosine-hydroxylase (clone 2/40/15) and dopamine-beta-hydroxylase in some neoplastic ganglion cells. In this study, synaptophysin was the most reliable neuronal marker. For immunocytochemical identification of neoplastic neurons in ganglioglioma as well as other tumors with neuronal differentiation the authors propose a panel of well-characterized monoclonal antibodies against neurofilament polypeptides, synaptophysin, and chromogranin A to support the histomorphologic diagnoses.