BackgroundAngiosarcoma is a histologically and molecularly heterogeneous vascular neoplasm with aggressive clinical behavior. Emerging data suggests that immune checkpoint blockade (ICB) is efficacious against some angiosarcomas, particularly cutaneous angiosarcoma of the head and neck (CHN).MethodsPatients with histologically confirmed angiosarcoma treated with ICB-based therapy at a comprehensive cancer center were retrospectively identified. Clinical characteristics and the results of targeted exome sequencing, transcriptome sequencing, and immunohistochemistry analyses were examined for correlation with clinical benefit. Durable clinical benefit was defined as a progression-free survival (PFS) of ≥16 weeks.ResultsFor the 35 patients included in the analyses, median PFS and median overall survival (OS) from the time of first ICB-based treatment were 11.9 (95% CI 7.4 to 31.9) and 42.5 (95% CI 19.6 to 114.2) weeks, respectively. Thirteen patients (37%) had PFS ≥16 weeks. Clinical factors associated with longer PFS and longer OS in multivariate analyses were ICB plus other therapy regimens, CHN disease, and white race. Three of 10 patients with CHN angiosarcoma evaluable for tumor mutational burden (TMB) had a TMB ≥10. Five of six patients with CHN angiosarcoma evaluable for mutational signature analysis had a dominant mutational signature associated with ultraviolet (UV) light. No individual gene or genomic pathway was significantly associated with PFS or OS; neither were TMB or UV signature status. Analyses of whole transcriptomes from nine patient tumor samples found upregulation of angiogenesis, inflammatory response, and KRAS signaling pathways, among others, in patients with PFS ≥16 weeks, as well as higher levels of cytotoxic T cells, dendritic cells, and natural killer cells. Patients with PFS <16 weeks had higher numbers of cancer-associated fibroblasts. Immunohistochemistry findings for 12 patients with baseline samples available suggest that neither PD-L1 expression nor presence of tumor-infiltrating lymphocytes at baseline appears necessary for a response to ICB-based therapy.ConclusionsICB-based therapy benefits only a subset of angiosarcoma patients. Patients with CHN angiosarcoma are more likely to have PFS ≥16 weeks, a dominant UV mutational signature, and higher TMB than angiosarcomas arising from other primary sites. However, clinical benefit was seen in other angiosarcomas also and was not restricted to tumors with a high TMB, a dominant UV signature, PD-L1 expression, or presence of tumor infiltrating lymphocytes at baseline.
Diabetes mellitus can lead to a diverse array of systemic complications. Poorly managed hyperglycemia can result in serious neurological consequences ranging from peripheral neuropathy to seizures and coma. A rare neurologic disorder seen in acute decompensated type 2 diabetes mellitus (T2DM) is hemichorea-hemiballismus (HCHB). HCHB is a movement disorder primarily associated with cerebrovascular accidents of infarct or hemorrhagic origin. It is a condition that can occur in a diabetic patient, especially when no other signs or symptoms of hyperglycemia are present. It is urgent to recognize HCHB movement disorder quickly as it may be the only presenting sign of hyperglycemia and can alert medical personnel to a possible hyperosmolar hyperglycemic state (HHS). We report an unusual case of HCHB in a patient with HHS, whose only presenting sign was unilateral hyperkinesis, which completely resolved after adequate blood glucose control. Prompt treatment and management of hyperglycemia yields an excellent prognosis in HCHB.
Background: The early phase of the coronavirus disease 2019 (COVID-19) pandemic had a negative impact on the wellness of hospitalists and hospital medicine advanced practice providers (APPs). However, the burden of the pandemic has evolved and the change in hospitalist and hospital medicine APP wellness is unknown.Objective: To evaluate the longitudinal trend in wellness of hospitalists and hospital medicine APPs during the COVID-19 pandemic and guide wellness interventions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.