Impact of Sun Exposure and Tanning Patterns on Next-Generation Sequencing Mutations in Melanoma.

BACKGROUND: For the past 30 y, the incidence rate of malignant melanoma has risen steadily. Ultraviolet radiation exposure has been identified as the most prevalent modifiable risk factor for melanoma. Here, next-generation sequencing was used to analyze the relationship between multiple sun exposure factors and select cancer-related genes to determine the relationship of sun exposure on the molecular profiles of melanomas. METHODS: The collection and analysis of study samples were approved by the institutional review board. The patient cohort consisted of 173 patients whose melanoma tissue samples underwent next-generation sequencing analysis for somatic mutations of 50 cancer-related genes. Univariate and multivariate analyses were conducted. RESULTS: Patients with a history of blistering sunburn had an absolute mutation incidence of 1.67 mutations per patient, compared with patients without a history of blistering sunburn, who had an absolute mutation incidence of 1.16 mutations per patient (P = 0.028). A BRAF mutation was found in more tumors of patients who reported visiting a tanning salon (57.14%), compared with those who had not (18.75%; P = 0.0463). Patients with a previous history of skin cancer were more likely to have a CDKN2A mutation (20.83%), compared with those without a previous history of skin cancer (7.76%; P = 0.0292). CONCLUSIONS: The trends seen in the molecular profiles of melanomas with respect to various sun exposure factors suggest that sun exposure impacts genetic makeup. Considering the increase in absolute mutation incidence in patients with a history of blistering sunburn suggests that additional genes may contribute to the pathology of malignancy. Future studies will use the unique molecular profiles of melanomas to personalize patient treatments.

COVID-19-Related Circumstances for Hospital Readmissions: A Case Series From 2 New York City Hospitals.

OBJECTIVE: The aim of the study was to determine the main factors contributing to hospital readmissions and their potential preventability after a coronavirus disease 2019 (COVID-19) hospitalization at 2 New York City hospitals. METHODS: This was a retrospective study at 2 affiliated New York City hospitals located in the Upper East Side and Lower Manhattan neighborhoods. We performed case reviews using the Hospital Medicine Reengineering Network framework to determine potentially preventable readmissions among patients hospitalized for COVID-19 between March 3, 2020 (date of first case) and April 27, 2020, and readmitted to either of the 2 hospitals within 30 days of discharge. RESULTS: Among 53 readmissions after hospitalization for COVID-19, 44 (83%) were deemed not preventable and 9 (17%) were potentially preventable. Nonpreventable readmissions were mostly due to disease progression or complications of COVID-19 (37/44, 84%). Main factors contributing to potentially preventable readmissions were issues with initial disposition (5/9, 56%), premature discharge (3/9, 33%), and inappropriate readmission (1/9, 11%) for someone who likely did not require rehospitalization. CONCLUSIONS: Most readmissions after a COVID-19 hospitalization were not preventable and a consequence of the natural progression of the disease, specifically worsening dyspnea or hypoxemia. Some readmissions were potentially preventable, mostly because of issues with disposition that were directly related to challenges posed by the ongoing COVID-19 pandemic. Clinicians should be aware of challenges with disposition related to circumstances of the COVID-19 pandemic.

Primary tumor characteristics and next-generation sequencing mutations as biomarkers for melanoma immunotherapy response.

INTRODUCTION: Considerable advances in melanoma have been realized through immunotherapy. The principal aim was to determine whether primary tumor characteristics or next-generation sequencing (NGS) could serve as markers of immunotherapy response. METHODS AND RESULTS: The study cohort consisted of 67 patients who received immunotherapy for recurrent or metastatic melanoma and for whom primary tumor biopsies and pathology reports were available. A subset of 59 patient tumors were profiled using an NGS panel of 50 cancer-related genes. Objective response rate to immunotherapy was assessed using RECIST v1.1 criteria. Progression-free survival (PFS) and overall survival (OS) were used as endpoints. Lymphovascular invasion (LVI) strongly correlated with an increased proportion of immunotherapy responders (p = .002). PFS interval (p = .003) and OS (p = .036) were significantly higher in patients with LVI. NRAS mutation was more strongly correlated with an increased proportion of immunotherapy responders (p =.050). PFS was significantly higher in patients with NRAS mutation (p = .042); no difference in OS (p = .111). DISCUSSION: This analysis demonstrates an association between lymphovascular invasion and immunotherapy response. Additionally, NGS mutation analysis demonstrated a potential association between NRAS mutations and immunotherapy response.