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Melanoma brain metastasis (MBM) frequently occurs in patients with advanced melanoma; yet, our understanding of the underlying salient biology is rudimentary. Here, we performed single-cell/nucleus RNA-seq in 22 treatment-naive MBMs and 10 extracranial melanoma metastases (ECMs) and matched spatial single-cell transcriptomics and T cell receptor (TCR)-seq. Cancer cells from MBM were more chromosomally unstable, adopted a neuronal-like cell state, and enriched for spatially variably expressed metabolic pathways. Key observations were validated in independent patient cohorts, patient-derived MBM/ECM xenograft models, RNA/ATAC-seq, proteomics, and multiplexed imaging. Integrated spatial analyses revealed distinct geography of putative cancer immune evasion and evidence for more abundant intra-tumoral B to plasma cell differentiation in lymphoid aggregates in MBM. MBM harbored larger fractions of monocyte-derived macrophages and dysfunctional TOX+CD8+ T cells with distinct expression of immune checkpoints. This work provides comprehensive insights into MBM biology and serves as a foundational resource for further discovery and therapeutic exploration.

Introduction: This study evaluates the feasibility of using a volunteer research associate (RA) to administer two separate health literacy assessment tools in the emergency department (ED), specifically in an older population of patients. The outcomes measured were administration time and interruptions.Methods: Using a prospective, cross-sectional study with a convenience sample, adult patients over the age of 55 presenting between June–August 2018 to one urban, academic ED were evaluated by a volunteer RA using either the Newest Vital Sign (NVS) or the Short Assessment of Health Literacy (SAHL). All patients 55 years of age or older who consented to participate were included. We excluded from this study the following: patients with dementia or other disability involving reading, speech, or cognitive function, as noted in their medical record or by their attending physician; prisoners; and those subjectively deemed in extremis or too ill to participate by their attending physician.Results: Health literacy was assessed in 202 patients using either the NVS or SAHL. Mean time of administration was 214.0 seconds for the NVS, and 206.8 for the SAHL. The maximum time of administration for the NVS was 563 seconds, compared to 607 seconds for the SAHL. We found that 95.2% of NVS and 93.9% of SAHL tests incurred no interruptions during administration.Conclusion: No significant difference was found between the length of time needed to administer the NVS or SAHL to older patients in the ED. Both tools averaged an administration time of around three to four minutes, and neither incurred regular interruptions to its administration by a volunteer RA. Further study is needed to assess validity of these tools in an ED setting.

Introduction: This study evaluates the feasibility of using a volunteer research associate (RA) to administer two separate health literacy assessment tools in the emergency department (ED), specifically in an older population of patients. The outcomes measured were administration time and interruptions.Methods: Using a prospective, cross-sectional study with a convenience sample, adult patients over the age of 55 presenting between June–August 2018 to one urban, academic ED were evaluated by a volunteer RA using either the Newest Vital Sign (NVS) or the Short Assessment of Health Literacy (SAHL). All patients 55 years of age or older who consented to participate were included. We excluded from this study the following: patients with dementia or other disability involving reading, speech, or cognitive function, as noted in their medical record or by their attending physician; prisoners; and those subjectively deemed in extremis or too ill to participate by their attending physician.Results: Health literacy was assessed in 202 patients using either the NVS or SAHL. Mean time of administration was 214.0 seconds for the NVS, and 206.8 for the SAHL. The maximum time of administration for the NVS was 563 seconds, compared to 607 seconds for the SAHL. We found that 95.2% of NVS and 93.9% of SAHL tests incurred no interruptions during administration.Conclusion: No significant difference was found between the length of time needed to administer the NVS or SAHL to older patients in the ED. Both tools averaged an administration time of around three to four minutes, and neither incurred regular interruptions to its administration by a volunteer RA. Further study is needed to assess validity of these tools in an ED setting.