Tips, Trends, and Truths: A Study of Psoriasis Treatment Content on TikTok.

INTRODUCTION: With more than two billion downloads since its launch, TikTok is the fastest-growing video-sharing platform in the world. Many people turn to TikTok for dermatologic medical information. However, there is limited data about psoriasis and psoriasis treatment content on this social media platform. OBJECTIVE: To compare the viewer engagement, content quality, and viewer experience of psoriasis treatment TikTok videos between physicians and non-physicians. METHODS: We searched the terms "psoriasis" and "psoriasis treatment" on TikTok. Video characteristics were collected. Content quality was evaluated using DISCERN. Viewer experience was assessed using the AVA. RESULTS: Viewer engagement did not significantly differ between physicians and non-physician content creators (0.033 plus/minus 0.005 vs 0.047 plus/minus 0.001, P=0.066). Compared to non-physicians, physicians created videos of higher quality (DISCERN: 1.76 plus/minus 0.058 vs 1.44 plus/minus 0.032, P<0.001) and of greater viewer experience (AVA: 2.55 plus/minus 0.183 vs 1.96 plus/minus 0.081, P=0.001). However, there is room for improvement in terms of creating videos of higher quality by both physicians and non-physicians. CONCLUSION: TikTok can be a powerful tool to promote health literacy and dispel misinformation. Dermatologists may consider focusing their efforts on creating comprehensive educational content and incorporating trending features to reach a wider audience. J Drugs Dermatol. 2024;23(2): doi:10.36849/JDD.7050e.

TROPION-Breast01: Datopotamab deruxtecan vs chemotherapy in pre-treated inoperable or metastatic HR+/HER2- breast cancer.

Improving the prognosis for patients with metastatic HR+/HER2- breast cancer remains an unmet need. Patients with tumors that have progressed on endocrine therapy and/or are not eligible for endocrine therapy had limited treatment options beyond chemotherapy. Antibody-drug conjugates are a novel and promising treatment class in this setting. Datopotamab deruxtecan (Dato-DXd) consists of a TROP2-directed humanized IgG1 monoclonal antibody attached via a serum-stable cleavable linker to a topoisomerase I inhibitor payload. TROPION-Breast01 is an ongoing phase III study that is evaluating the efficacy and safety of Dato-DXd compared with investigator's choice of standard-of-care chemotherapy in patients with inoperable or metastatic HR+/HER2- breast cancer who have received one or two prior lines of systemic chemotherapy in the inoperable or metastatic setting. Clinical Trial Registration: NCT05104866 (ClinicalTrials.gov).

Antibody-drug conjugates are a type of drug with two parts: an antibody that directs the drug to the cancer cells and a cancer-cell killing toxic payload. By binding to cancer cells before releasing the payload, treatment is directed to the site of action so there are fewer side effects in the rest of the body. Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugates made up of datopotamab (antibody) and DXd (payload) which are joined together via a stable linker. Datopotamab binds to a protein found on cancer cells called TROP2; it then goes inside and releases the DXd payload to kill the tumor cells. DXd may leak out to surrounding cancer cells and kill those as well. The TROPION-Breast01 study is comparing Dato-DXd with standard-of-care chemotherapy. Around 700 patients will take part, who have: Tumors that cannot be surgically removed. Tumors that are hormone receptor-positive and do not have HER2 overexpression. Had one or two lines of previous chemotherapy (after the tumor could not be surgically removed, or had spread). Had tumor growth despite hormonal therapy or are ineligible for hormonal therapy. Patients who meet the entry criteria will be randomly assigned to a treatment group in equal numbers to either Dato-DXd or an appropriate chemotherapy, out of four options chosen by the treating doctor. At the end of the study, researchers will look at whether the patients who receive Dato-DXd live longer without their breast cancer getting worse, compared with patients who receive chemotherapy. This study is also looking at how the treatment affects patients' quality of life.

No Racial Differences Found in Access to Biologics: A Population-Based Study of Psoriasis Patients in the United States.

BACKGROUND: Conflicting evidence exists regarding the role of race in access to biologics for patients with psoriasis. OBJECTIVE: To compare biologic use among adult and pediatric United States psoriasis patients of different racial backgrounds. METHODS: Population-based study of US psoriasis patients using the 2003 to 2018 Medical Expenditure Panel Survey (MEPS). RESULTS: Among 31,525,500 adults and children with psoriasis (weighted), 3,026,578 (9.6%) were on biologics. Among psoriasis patients, 27,464,864 (87.1%) self-identified as white, 2,033,802 (6.5%) self-identified as Black, 1,173,435 (3.7%) self-identified as Asian or Pacific Islander, and 853,399 (2.7%) self-identified as other races. Among those on biologics, 2,778,239 (91.8%) self-identified as white, 84,971 (2.8%) identified as Black, 89,452 (3.0%) self-identified as Asian or Pacific Islander, and 73,917 (2.4%) self-identified as other races. Multivariate logistic regression revealed no significant differences in biologic access between whites and non-whites after adjusting for sociodemographic factors including insurance status (OR for Blacks: 0.347 [0.118, 1.021], P=0.055; OR for Asians: 0.616 [0.240, 1.579], P=0.311; OR for other races: 0.850 [0.216, 3.336], P=0.814. CONCLUSION: The results of this study suggest that race alone is not independently associated with access to biologics among adult US psoriasis patients. Additional studies are necessary to evaluate factors independently associated with biologics access among adults and children with psoriasis in the US. J Drugs Dermatol. 2023;22(8):835-837. doi:10.36849/JDD.7134 Reddy R, Khan S, Yee D, et al. No racial differences found in access to biologics: a population-based study of psoriasis patients in the United States. .

Cutaneous leiomyosarcoma: a retrospective review of 45 cases.

Primary cutaneous leiomyosarcoma (LMS) is a rare soft tissue tumour type with two subtypes, dermal and subcutaneous. As deeper tumours confer a worse prognosis, they require a more aggressive approach. Conversely, a more conservative surgical approach for dermal LMS has been suggested. Few studies have comprehensively reported both clinical surgical and histological excision margins. Therefore, we sought to provide margin recommendations based on our experience and review of the existing literature. We undertook a retrospective case-note review (1998-2019) of cutaneous LMS management to establish histological/surgical margins using pathology/electronic patient records. The diagnosis was made and classified by an experienced dermatopathologist according to the World Health Organization classification. In the dermal LMS cohort (n = 35), mean peripheral and deep histological margins were 5.4 mm (range 0.5-20) and 5.6 mm (range 0.1-14.5), respectively. The incomplete excision rate was 31% (11 of 35). There were no recurrences. In the subcutaneous LMS cohort (n = 10), mean peripheral and deep histological margins were 5.7 mm (range 0.2-14) and 1.1 mm (range 0.2-1.7), respectively. The incomplete excision rate was 40% (4 of 10). The recurrence rate was 20% (2 of 10) despite achieving histological clearance after 1 year. One lung metastasis occurred 1 year following an adequately excised primary scalp LMS. Thus, for dermal LMS we propose a clinical margin of 5-10 mm (depending on lesion size) at the initial excision or at scar re-excision following involved/close histological peripheral and/or deep margins (i.e. < 1 mm). For subcutaneous LMS, we suggest a clinical margin of 15-20 mm (depending on lesion size) to achieve a peripheral histological clearance of 10 mm and negative deep margin (i.e. > 1 mm), down to the periosteum/fascia/muscle according to anatomical site. If this is not achieved, a re-excision would be recommended. However, prospective studies are needed for optimal guidance.

Differences in accessing dermatology offices, primary care offices, and emergency departments between Hispanics and Non-Hispanic White Patients.

How Hispanic patients access dermatologic care for skin diseases is unknown. This study aims to determine if differences exist in accessing the emergency department (ED), primary care, and outpatient dermatologic offices for skin diseases between Hispanic and non-Hispanic White patients. This cross-sectional study used nationally representative data from the Medical Panel Expenditure Survey (MEPS) from 2016-2019. A total of 109,337,668 (weighted) patients with any skin disease diagnosed at an ED, primary care, or dermatology visit were identified. Hispanics comprised 13.0% and non-Hispanic Whites comprised 68.8% of this subpopulation. Overall, 94.1% of Hispanic patients attended a primary care visit for their skin complaint, 5.8% saw a dermatologist, and 0.1% attended an ED visit. Compared to non-Hispanic Whites, Hispanics were more likely to attend a primary care visit (aOR 1.865; 95%CI, 1.640-2.122) and less likely to attend an outpatient dermatology visit (aOR 0.536; 95%CI, 0.471-0.610), after adjusting for insurance status, education, income, sex, age, and comorbidities. Our study suggests that, compared to non-Hispanic Whites, Hispanic patients access primary care more frequently and outpatient dermatologic offices less frequently for their skin conditions. Language barriers, less familiarity with the healthcare system, and lack of adequate health insurance may play roles in this observation.

Evaluating Sentiment, Engagement, and Perception of Biologics Among Patients with Psoriasis and Psoriatic Arthritis on Reddit.

BACKGROUND: Limited analyses of social media content among psoriasis (PsO) and psoriatic arthritis (PsA) patients exist. These patients may turn to social media to gain insight into treatments such as biologics. OBJECTIVES: This study aims to analyze the content, sentiment, and engagement of social media posts regarding biologics for PsO and PsA. METHODS: Posts and comments discussing biologics were extracted from publicly accessible PsO and PsA Reddit groups. Posts were assigned higher (HOT) and lower order (LOT) themes, sentiments, and engagement scores. RESULTS: Of 1141 posts extracted, 705 posts were classified under the HOT general/efficacy. Twelve lower order themes (LOTs) were identified: general advice/experience (10.2%), symptoms improved (36.6%), switching biologics (10.5%), and time to results (13.4%). 61.3% of content was of positive sentiment, 24.0% was neutral, and 14.7% was of negative sentiment. The mean sentiment score, defined as the average of all posts' sentiment scores (where negative=-1, neutral=0, and positive=1), was overall positive at 0.47, 95% CI [.41-.52]. Mean sentiment scores between LOTs were significantly different (P<0.001). Information regarding biologics on Reddit is mostly positive; however, there remains a significant number of users expressing dissatisfaction with their efficacy or with biologics in general. Many users sought anecdotal advice. CONCLUSION: These findings can help guide educational efforts to anticipate concerns and appease hesitancy regarding biologics and their efficacy. J Drugs Dermatol. 2023;22(3):306-309. doi:10.36849/JDD.7124.

Disease-driven engineering of peptide-targeted DM1 loaded liposomal nanoparticles for enhanced efficacy in treating multiple myeloma by exploring DM1 prodrug chemistry.

Here, we report a CD138 receptor targeting liposomal formulation (TNP[Prodrug-4]) that achieved efficacious tumor growth inhibition in treating multiple myeloma by overcoming the dose limiting severe toxicity issues of a highly potent drug, Mertansine (DM1). Despite the promising potential to treat various cancers, due to poor solubility and pharmacokinetic profile, DM1's translation to the clinic has been unsatisfactory. We hypothesized that the optimal prodrug chemistry would promote efficient loading of the prodrug into targeted nanoparticles and achieve controlled release following endocytosis by the cancer cells, consequently, accomplish the most potent tumor growth inhibition. We evaluated four functional linker chemistries for synthesizing DM1-Prodrug molecules and evaluated their stability and cancer cell toxicity in vitro. It was determined that the phosphodiester moiety, as part of nanoparticle formulations, demonstrated most favorable characteristics with an IC50 of ∼16 nM. Nanoparticle formulations of Prodrug-4 enabled its administration at 8-fold higher dosage of equivalent free drug while remaining below maximum tolerated dose. Importantly, TNP[Prodrug-4] achieved near complete inhibition of tumor growth (∼99% by day 10) compared to control, without displaying noticeable systemic toxicity. TNP[Prodrug-4] promises a formulation that could potentially make DM1 treatment available for wider clinical applications with a long-term goal for better patient outcomes.

"I'm Off My Meds": Public Perception of Interactions Between SARS-CoV-2 Vaccines and Anti-Psoriatic Treatments Online.

IMPORTANCE: Psoriasis patients may seek information about the SARS-CoV-2 vaccine and their diagnosis from social media platforms. Analyses of social media interactions may help guide dermatologists’ educational efforts during this pandemic. OBJECTIVES: This study analyzed the content and sentiment of online social media posts about the medication interaction between SARS-CoV-2 vaccines and anti-psoriatic therapies among psoriasis patients. DESIGN: Publicly accessible Facebook and Reddit groups regarding psoriasis and psoriatic arthritis were identified. Posts uploaded between March 1, 2021, and July 31, 2021, with information about the SARS-CoV-2 vaccine and psoriasis and psoriatic arthritis, were extracted. Themes, sentiment scores, and engagement scores were assigned to each post. RESULTS: 477 posts contained content pertaining to the vaccine and psoriatic medications. 19 (4%) of the posts contain negative sentiment, 232 (48.6%) contain neutral sentiment, and 226 (47.4%) contain positive sentiment. Several themes emerged from this study. A majority of posts (32.5%) contained concerns about holding or stopping medications prior to obtaining the vaccine. Other common concerns included fear of negative reaction (21.8%) and uncertainty about the ability to generate an efficient immune response to the vaccine while on anti-psoriatic medications (19.9%). CONCLUSIONS AND RELEVANCE: Concerns identified by our content analysis should be incorporated into education efforts to address the reasons for vaccine hesitancy among patients with psoriatic diseases. These patient concerns can also help guide our strategy for implementing evidence-based recommendations on COVID-19 vaccination. J Drugs Dermatol. 2022;21(8):901-905. doi:10.36849/JDD.6853.

Biologics to breast milk: A cross-sectional study of popular eczema treatment content on TikTok.

We conducted a cross-sectional study to compare viewer engagement, content quality and viewer experience of eczema related medical content on TikTok between health care professionals and non-health care professionals. Compared to non-health care professionals, health care professionals created videos of higher quality and superior viewing experience. Viewer engagement did not differ significantly between videos made by health care professionals and non-health care professionals. Overall, content creators should focus on producing comprehensive, evidence-based videos.

Orbital and In-Situ Investigation of Periodic Bedrock Ridges in Glen Torridon, Gale Crater, Mars.

Gale crater, the field site for NASA's Mars Science Laboratory Curiosity rover, contains a diverse and extensive record of aeolian deposition and erosion. This study focuses on a series of regularly spaced, curvilinear, and sometimes branching bedrock ridges that occur within the Glen Torridon region on the lower northwest flank of Aeolis Mons, the central mound within Gale crater. During Curiosity's exploration of Glen Torridon between sols ∼2300-3080, the rover drove through this field of ridges, providing the opportunity for in situ observation of these features. This study uses orbiter and rover data to characterize ridge morphology, spatial distribution, compositional and material properties, and association with other aeolian features in the area. Based on these observations, we find that the Glen Torridon ridges are consistent with an origin as wind-eroded bedrock ridges, carved during the exhumation of Mount Sharp. Erosional features like the Glen Torridon ridges observed elsewhere on Mars, termed periodic bedrock ridges (PBRs), have been interpreted to form transverse to the dominant wind direction. The size and morphology of the Glen Torridon PBRs are consistent with transverse formative winds, but the orientation of nearby aeolian bedforms and bedrock erosional features raise the possibility of PBR formation by a net northeasterly wind regime. Although several formation models for the Glen Torridon PBRs are still under consideration, and questions persist about the nature of PBR-forming paleowinds, the presence of PBRs at this site provides important constraints on the depositional and erosional history of Gale crater.

Mouse pulmonary interstitial macrophages mediate the pro-tumorigenic effects of IL-9.

Although IL-9 has potent anti-tumor activity in adoptive cell transfer therapy, some models suggest that it can promote tumor growth. Here, we show that IL-9 signaling is associated with poor outcomes in patients with various forms of lung cancer, and is required for lung tumor growth in multiple mouse models. CD4+ T cell-derived IL-9 promotes the expansion of both CD11c+ and CD11c- interstitial macrophage populations in lung tumor models. Mechanistically, the IL-9/macrophage axis requires arginase 1 (Arg1) to mediate tumor growth. Indeed, adoptive transfer of Arg1+ but not Arg1- lung macrophages to Il9r-/- mice promotes tumor growth. Moreover, targeting IL-9 signaling using macrophage-specific nanoparticles restricts lung tumor growth in mice. Lastly, elevated expression of IL-9R and Arg1 in tumor lesions is associated with poor prognosis in lung cancer patients. Thus, our study suggests the IL-9/macrophage/Arg1 axis is a potential therapeutic target for lung cancer therapy.

Liposomal Targeting Modifies Endosomal Escape: Design and Mechanistic Implications.

Development of effective targeted nanoparticle (TNP) therapeutics requires rational design of targeted and endosomolytic moieties. Nevertheless, endosomal escape of TNPs is poorly understood, relying on extrapolation of knowledge from nontargeted (NP) systems. Here, we describe how incorporation of targeting elements on endosomolytic nanoparticles alters the endosomal escape mechanism. We demonstrated that NP and TNP systems react differently to addition of precise length oligohistidines and showcase the effects of alternating spatial arrangements of targeting and endosomolytic elements. The results established that these elements act cooperatively and must be incorporated as individual moieties, rather than a single multifunctional moiety, for optimal internalization by target cells.

Identification and optimization of tunable endosomal escape parameters for enhanced efficacy in peptide-targeted prodrug-loaded nanoparticles.

Endosomal escape of nanoparticles (NPs) is a weighty consideration for engineering successful nanomedicines. Although it is well-established that incorporation of histidine (His) in particle design improves endosomal escape for NPs, our understanding of its effects for ligand-targeted nanoparticles (TNPs) remains incomplete. Here, we systematically evaluated the cooperativity between targeting ligands and endosomolytic elements using liposomal TNPs with precise stoichiometric control over functional moieties (>90% loading efficiency). We synthesized endosomolytic lipid conjugates consisting of 1 to 10 consecutive His residues presented at the end of linkers between 2 to 45 repeating units of ethylene glycol (Hisn-EGm). Hisn-EGm had minimal effect on NP size (∼115 nm) and had no significant effect on the receptor specificity of TNPs (>90% inhibition by competing peptide). We evaluated various formulations with 8 different targeting ligands relevant to two disease models. Incorporation of His1-EG8 resulted in up to ∼170- and ∼12.9-fold enhancement in intracellular accumulation relative to non-endosomolytic NP and TNP, respectively. These observations were time-dependent, targeted receptor-dependent, and showed different trends for NPs and TNPs. Further evaluation demonstrated short linkers (EG2-4) significantly enhanced nanoparticle internalization compared to EG8 or longer by up to ∼2.5-fold. Finally, rationally optimized formulation, His1-EG2-TNP, improved in vitro toxicity of a DM1 prodrug to SK-BR-3 cells by ∼4.2-fold, with IC50 ∼8.5 nM compared to ∼36 nM for no-His TNP, and >100 nM for non-targeted/no-His NP. This study uncovers an intricate relationship between endosomal escape and ligand-targeted drug delivery, as well as tunable parameters. Furthermore, our findings highlight the value of rational design and systematic analysis for optimization of multifunctional NPs.

Characterization of Clasts in the Glen Torridon Region of Gale Crater Observed by the Mars Science Laboratory Curiosity Rover.

The morphology and composition of clasts have the potential to reveal the nature and extent of erosional processes acting in a region. Dense accumulations of granule- to pebble-sized clasts covering the ground throughout the Glen Torridon region of Gale crater on Mars were studied using data acquired by the Mars Science Laboratory Curiosity rover between sols 2300 and 2593. In this study, measurements of shape, size, texture, and elemental abundance of unconsolidated granules and pebbles within northern Glen Torridon were compiled. Nine primary clast types were identified through stepwise hierarchical clustering, all of which are sedimentary and can be compositionally linked to local bedrock, suggesting relatively short transport distances. Several clast types display features associated with fragmentation along bedding planes and existing cracks in bedrock. These results indicate that Glen Torridon clasts are primarily the product of in-situ physical weathering of local bedrock.