Circulating Tumor DNA Assay Detects Merkel Cell Carcinoma Recurrence, Disease Progression, and Minimal Residual Disease: Surveillance and Prognostic Implications.

PURPOSE: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a 40% recurrence rate, lacking effective prognostic biomarkers and surveillance methods. This prospective, multicenter, observational study aimed to evaluate circulating tumor DNA (ctDNA) as a biomarker for detecting MCC recurrence. METHODS: Plasma samples, clinical data, and imaging results were collected from 319 patients. A tumor-informed ctDNA assay was used for analysis. Patients were divided into discovery (167 patients) and validation (152 patients) cohorts. Diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed. RESULTS: ctDNA showed high sensitivity, 95% (discovery; 95% CI, 87 to 99) and 94% (validation; 95% CI, 85 to 98), for detecting disease at enrollment, with corresponding specificities of 90% (95% CI, 82 to 95) and 86% (95% CI, 77 to 93). A positive ctDNA during surveillance indicated increased recurrence risk, with hazard ratios (HRs) of 6.8 (discovery; 95% CI, 2.9 to 16) and 20 (validation; 95% CI, 8.3 to 50). The PPV for clinical recurrence at 1 year after a positive ctDNA test was 69% (discovery; 95% CI, 32 to 91) and 94% (validation; 95% CI, 71 to 100), respectively. The NPV at 135 days after a negative ctDNA test was 94% (discovery; 95% CI, 90 to 97) and 93% (validation; 95% CI, 89 to 97), respectively. Patients positive for ctDNA within 4 months after treatment had higher rates of recurrence, with 1-year rates of 74% versus 21% (adjusted HR, 7.4 [95% CI, 2.7 to 20]). CONCLUSION: ctDNA testing exhibited high prognostic accuracy in detecting MCC recurrence, suggesting its potential to reduce frequent surveillance imaging. ctDNA also identifies high-risk patients who need more frequent imaging and may be best suited for adjuvant therapy trials.

Impaired innate and adaptive immune responses to BNT162b2 SARS-CoV-2 vaccination in systemic lupus erythematosus.

Understanding the immune responses to SARS-CoV-2 vaccination is critical to optimizing vaccination strategies for individuals with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here, we comprehensively analyzed innate and adaptive immune responses in 19 patients with SLE receiving a complete 2-dose Pfizer-BioNTech mRNA vaccine (BNT162b2) regimen compared with a control cohort of 56 healthy control (HC) volunteers. Patients with SLE exhibited impaired neutralizing antibody production and antigen-specific CD4+ and CD8+ T cell responses relative to HC. Interestingly, antibody responses were only altered in patients with SLE treated with immunosuppressive therapies, whereas impairment of antigen-specific CD4+ and CD8+ T cell numbers was independent of medication. Patients with SLE also displayed reduced levels of circulating CXC motif chemokine ligands, CXCL9, CXCL10, CXCL11, and IFN-γ after secondary vaccination as well as downregulation of gene expression pathways indicative of compromised innate immune responses. Single-cell RNA-Seq analysis reveals that patients with SLE showed reduced levels of a vaccine-inducible monocyte population characterized by overexpression of IFN-response transcription factors. Thus, although 2 doses of BNT162b2 induced relatively robust immune responses in patients with SLE, our data demonstrate impairment of both innate and adaptive immune responses relative to HC, highlighting a need for population-specific vaccination studies.

Twitch user perceptions, attitudes and behaviours in relation to food and beverage marketing on Twitch compared with YouTube.

Influencer marketing may be amplified on livestreaming platforms (e.g., Twitch) compared with asynchronous social media (e.g., YouTube). However, food and beverage marketing on Twitch has not been evaluated at a user level. The present study aimed to compare users' self-reported exposure to food marketing and associated attitudes, consumption and purchasing behaviours on Twitch compared with YouTube. A survey administered via social media was completed by 621 Twitch users (90 % male, 64 % white, 69 % under 25 years old). Of respondents, 72 % recalled observing at least one food or beverage advertisement on Twitch. There were significant differences in the recall of specific brands advertised on Twitch (P < 0⋅01). After observing advertised products, 14 % reported craving the product and 8 % reported purchasing one. In chat rooms, 56 % observed conversations related to food and 25 % participated in such conversations. There were significant differences in the number of users who consumed various products while watching Twitch (P < 0⋅01). Of users who frequented YouTube (n 273), 65 % reported negative emotions when encountering advertising on YouTube compared with 40 % on Twitch (P < 0⋅01). A higher proportion felt Twitch's advertising primarily supported content creators (79 v. 54 %, P < 0⋅01), while a higher proportion felt that YouTube's advertising primarily supported the platform (49 v. 66 %, P < 0⋅01). The findings support that food marketing exposures on Twitch are noticeable, less bothersome to users and influence consumption and purchasing behaviours. Future studies are needed to examine how the livestreaming environment may enhance advertising effectiveness relative to asynchronous platforms.

Promotion of Meal Premiums in Child-Directed TV Advertising for Children's Fast-food Meals.

BACKGROUND: Fast-food intake is a modifiable obesity risk factor in early childhood, and child-directed fast-food marketing is common. Per self-regulatory guidelines regarding deception, premiums (ie, incentives or toy giveaways) in child-directed advertisements must be secondary to the advertised product. METHODS: Content analyses were performed of all child-directed fast-food television (TV) advertisements aired on four national US children's TV networks, February 1, 2019, through January 31, 2020, to assess the emphasis of premiums relative to food. We quantified the percent of the audio transcript (word count) and visual airtime (seconds) that included premiums or food and the on-screen size of premiums relative to food in randomly selected frames from each advertisement. RESULTS: There were 28 unique child-directed advertisements for children's fast-food meals in the study year; 27 advertisements were from one restaurant and accounted for nearly all (99.8%) of the total airtime for the 28 advertisements. Premiums were present in 27 of the 28 unique advertisements. On average, premiums (versus food) accounted for 53.0% (vs 16.0%) of words in the audio transcript and 59.2% (vs 54.3%) of the visual airtime per advertisement. In the random subset of frames that includes both premiums and food imagery, imagery of premiums accounted for 9.7% (95% CI: 6.4%-13.0%) of the on-screen area, whereas imagery of food accounted for 5.7% (95% CI: 4.4%-7.0%), an average ratio of 1.9:1 within each frame when excluding one large outlier. CONCLUSIONS: Child-directed fast-food TV advertisements emphasize premiums over food in violation of self-regulatory guidelines, counter to childhood obesity prevention efforts.