Patient Preferences Regarding Virtual Visits in Cutaneous Surgery in the Era of COVID-19.

BACKGROUND: The COVID-19 pandemic has caused an increasing shift toward the utilization of telehealth services. There are limited data on patient preferences for these services in dermatologic surgery. OBJECTIVE: To evaluate patient preferences regarding telehealth in dermatologic surgery for pre- and postsurgical care. METHODS: A survey was administered to patients in an academic dermatology practice. RESULTS: Two hundred twenty-four patients participated. An in-person presurgical consultation was preferred by 62.1%, and a postsurgical in-person visit was preferred by 67.7%. The most commonly cited reason was desire for physical interaction with their surgeon. For each 10-year increase in age, there was a 1.26-fold and 1.12-fold increase in preference for in-person consultation and follow-up, respectively. Eighty-seven percent felt safe during office visit, and 41% reported no anxiety regarding fear of contracting COVID-19. The proportion of patients preferring in-person pre- or postsurgical visits was similar regardless of sex, presence of an immunocompromising condition, prior dermatologic surgery, anxiety level for contracting COVID-19, and perceived level of office safety. CONCLUSION: A majority of patients prefer in-person visits for pre- and postsurgical care. Older patients have a greater preference for in-person care. Anxiety level regarding COVID-19 and perceived level of office safety were not related to preference for in-person visits.

Survival differences in acral lentiginous melanoma according to socioeconomic status and race.

BACKGROUND: Relationships of socioeconomic status (SES) and race to survival in acral lentiginous melanoma (ALM) are poorly characterized. OBJECTIVE: To compare disease-specific survival in ALM across SES and race. METHODS: Retrospective cohort study using the Surveillance, Epidemiology, and End Results database, 2000 to 2016. RESULTS: We identified 2245 patients with a first ALM diagnosis. Five-year disease-specific survival was 77.8% (95% CI, 75.9%-79.9%). After adjustment, patients in the lowest and second-to-lowest SES quintile had 1.33 (95% CI, 0.90-1.96) and 1.42 (95% CI, 1.03-1.97) times the risk of death, respectively, compared to highest quintile patients. Hispanic White and Black patients had 1.48 (95% CI, 1.10-1.99) and 1.25 (95% CI, 0.88-1.79) times the risk of death, respectively, compared to non-Hispanic Whites. Hazard ratios for ALM-specific death decreased in Hispanic White and Black patients after adjusting for SES and American Joint Committee on Cancer stage at diagnosis. LIMITATIONS: Treatments could not be evaluated. SES was measured at the level of the census tract and does not account for individual level factors. CONCLUSION: Differences exist in ALM survival according to socioeconomic status and race. Differences in SES and American Joint Committee on Cancer stage at diagnosis contribute to survival disparities for Hispanic White and Black patients. Understanding factors driving survival disparities related to SES and race may improve ALM outcomes.

Novel immune signatures associated with dysplastic naevi and primary cutaneous melanoma in human skin.

Dysplastic naevi (DN) are benign lesions with atypical features intermediate between that of common melanocytic naevi (CMN) and malignant melanoma (MM). Debate remains over whether DN represent progressive lesions from CMN. Through gene expression profiling and analysis of molecular gene signatures, our study revealed progressive increases in immune activation and regulation, along with pathways implicated in melanomagenesis, from CMN to DN to MM. Using criteria of 1.5-fold change and false discovery rate ≤0.05, we found differential expression of 7186 probes (6370 unique genes) with the largest difference detected between DN and MM from the standpoint of genomic melanoma progression. Despite progressive increases in the T-helper type 1 (Th1)-inducing gene (IL-12), RT-PCR indicated impaired Th1 or cytotoxic T-cell response (decreased IFN-γ) in MM. Concordantly, our results indicated progressive increases in molecular markers associated with regulatory T cells, exhausted T cells and tolerogenic dendritic cells, including detection of increased expression of suppressor of cytokine signalling 3 (SOCS3) in dendritic cells associated with MM. All together, our findings suggest that the increased immunosuppressive microenvironment of melanoma may contribute to unhampered proliferation of neoplastic cells. In addition, the detection of increased markers associated with tolerogenic dendritic cells in MM suggests that targeting these suppressive immune cell types may represent an alternative avenue for future immunotherapy.

Discovery of the IL-23/IL-17 Signaling Pathway and the Treatment of Psoriasis.

Psoriasis vulgaris is a common, heterogeneous, chronic inflammatory skin disease characterized by thickened, red, scaly plaques and systemic inflammation. Psoriasis is also associated with multiple comorbid conditions, such as joint destruction, cardiovascular disease, stroke, hypertension, metabolic syndrome, and chronic kidney disease. The discovery of IL-17-producing T cells in a mouse model of autoimmunity transformed our understanding of inflammation driven by T lymphocytes and associations with human inflammatory diseases, such as psoriasis. Under the regulation of IL-23, T cells that produce high levels of IL-17 create a self-amplifying, feed-forward inflammatory response in keratinocytes that drives the development of thickened skin lesions infiltrated with a mixture of inflammatory cell populations. Recently, the Food and Drug Administration approved multiple highly effective psoriasis therapies that disrupt IL-17 (secukinumab, ixekizumab, and brodalumab) and IL-23 (guselkumab and tildrakizumab) signaling in the skin, thus leading to a major paradigm shift in the way that psoriatic disease is managed.

LIN28 binds messenger RNAs at GGAGA motifs and regulates splicing factor abundance.

LIN28 is a conserved RNA-binding protein implicated in pluripotency, reprogramming, and oncogenesis. It was previously shown to act primarily by blocking let-7 microRNA (miRNA) biogenesis, but here we elucidate distinct roles of LIN28 regulation via its direct messenger RNA (mRNA) targets. Through crosslinking and immunoprecipitation coupled with high-throughput sequencing (CLIP-seq) in human embryonic stem cells and somatic cells expressing exogenous LIN28, we have defined discrete LIN28-binding sites in a quarter of human transcripts. These sites revealed that LIN28 binds to GGAGA sequences enriched within loop structures in mRNAs, reminiscent of its interaction with let-7 miRNA precursors. Among LIN28 mRNA targets, we found evidence for LIN28 autoregulation and also direct but differing effects on the protein abundance of splicing regulators in somatic and pluripotent stem cells. Splicing-sensitive microarrays demonstrated that exogenous LIN28 expression causes widespread downstream alternative splicing changes. These findings identify important regulatory functions of LIN28 via direct mRNA interactions.

Integrative genome-wide analysis reveals cooperative regulation of alternative splicing by hnRNP proteins.

Understanding how RNA binding proteins control the splicing code is fundamental to human biology and disease. Here, we present a comprehensive study to elucidate how heterogeneous nuclear ribonucleoparticle (hnRNP) proteins, among the most abundant RNA binding proteins, coordinate to regulate alternative pre-mRNA splicing (AS) in human cells. Using splicing-sensitive microarrays, crosslinking and immunoprecipitation coupled with high-throughput sequencing (CLIP-seq), and cDNA sequencing, we find that more than half of all AS events are regulated by multiple hnRNP proteins and that some combinations of hnRNP proteins exhibit significant synergy, whereas others act antagonistically. Our analyses reveal position-dependent RNA splicing maps, in vivo consensus binding sites, a surprising level of cross- and autoregulation among hnRNP proteins, and the coordinated regulation by hnRNP proteins of dozens of other RNA binding proteins and genes associated with cancer. Our findings define an unprecedented degree of complexity and compensatory relationships among hnRNP proteins and their splicing targets that likely confer robustness to cells.