The mutational landscape of melanoma brain metastases presenting as the first visceral site of recurrence

Brain metastases are a major cause of melanoma-related mortality and morbidity. We undertook whole-exome sequencing of 50 tumours from patients undergoing surgical resection of brain metastases presenting as the first site of visceral disease spread and validated our findings in an independent dataset of 18 patients. Brain metastases had a similar driver mutational landscape to cutaneous melanomas in TCGA. However, KRAS was the most significantly enriched driver gene, with 4/50 (8%) of brain metastases harbouring non-synonymous mutations. Hotspot KRAS mutations were mutually exclusive from BRAF^V600, NRAS and HRAS mutations and were associated with a reduced overall survival from the resection of brain metastases (HR 10.01, p = 0.001). Mutations in KRAS were clonal and concordant with extracranial disease, suggesting that these mutations are likely present within the primary. Our analyses suggest that KRAS mutations could help identify patients with primary melanoma at higher risk of brain metastases who may benefit from more intensive, protracted surveillance.Subject terms: CNS cancer, Metastasis, Melanoma, Tumour biomarkers, Cancer     

Examining the vulnerability of ambivalent young adults to e-cigarette messages

Abstract

This study used a randomized online experiment to understand the interrelationships between e-cigarette benefit and harm perceptions, e-cigarette use ambivalence, and e-cigarette message exposure and perceived effectiveness. A high prevalence of ambivalent attitudes toward e-cigarettes at baseline was reported. Ambivalent individuals reported significantly higher benefits and lower harm perceptions compared to univalent individuals. Contrary to past findings, ambivalence was not responsive to persuasive messages in this study. This study situates e-cigarette use perceptions in a realistic setting. High baseline ambivalence in this study calls for more unequivocal messages from the FDA about the risks of e-cigarette use.     

New,Immunomodulatory, Oral Nutrition Formula for Use Prior to Surgery in Patients With Head and Neck Cancer: An Exploratory Study

Background: The perioperative use of immunomodulatory nutrition formulas in patients with head and neck cancer reduces the number of postoperative infections and the length of hospital stay. Objective: An exploratory, randomized, controlled, blind, clinical trial was designed to examine the effect of the preoperative consumption of a new, immunomodulatory, oral nutrition formula in patients with head and neck cancer. Methods: Thirty‐eight patients were randomized to receive either 400 mL/d of either the new immunomodulatory formula (IF) or that commonly used in clinical practice (CF) over 10 days prior to surgery. Thirty‐three patients completed the study. Compliance, tolerance, the length of hospital stay, the incidence of infections and noninfectious complications before discharge, and the same up to 15 and 30 days after discharge were recorded. Results: The percentage of patients who developed infections before discharge was significantly lower in the IF than in the CF group (P = .013), as was the number of infections/100 patients/d (P = .035). The length of hospital stay was significantly shorter in the IF group (P = .001). Both formulas were safe and well tolerated. No other differences were detected. These results suggest preoperative consumption of the new formula to be beneficial for patients with neck and head cancer. Further trials are needed to confirm these results and to test the efficacy of the formula in patients with other conditions. Conclusion: The new formula can be safely prescribed as part of the preoperative treatment of patients with head and neck cancer and might reduce the problem of postoperative infection.