Utilizing systems genetics to enhance understanding into molecular targets of skin cancer.

Despite progress made with immune checkpoint inhibitors and targeted therapies, skin cancer remains a significant public health concern in the United States. The intricacies of the disease, encompassing genetics, immune responses, and external factors, call for a comprehensive approach. Techniques in systems genetics, including transcriptional correlation analysis, functional pathway enrichment analysis, and protein-protein interaction network analysis, prove valuable in deciphering intricate molecular mechanisms and identifying potential diagnostic and therapeutic targets for skin cancer. Recent studies demonstrate the efficacy of these techniques in uncovering molecular processes and pinpointing diagnostic markers for various skin cancer types, highlighting the potential of systems genetics in advancing innovative therapies. While certain limitations exist, such as generalizability and contextualization of external factors, the ongoing progress in AI technologies provides hope in overcoming these challenges. By providing protocols and a practical example involving Braf, we aim to inspire early-career experimental dermatologists to adopt these tools and seamlessly integrate these techniques into their skin cancer research, positioning them at the forefront of innovative approaches in combating this devastating disease.

Prescribing Patterns of Dupilumab for Atopic Dermatitis in Adults: Retrospective, Observational Cohort Study.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory disease caused by a type 2 T helper cell-mediated immune response to environmental antigens. Approximately 1 in 5 patients with AD presents with moderate to severe disease, and treatments approved by the Food and Drug Administration include emollients, topical glucocorticoids, and calcineurin inhibitors. Dupilumab, a fully human monoclonal antibody, improves AD via inhibition of interleukin-4 and interleukin-13. OBJECTIVE: Our aim was to characterize the prescribing patterns of dupilumab for AD in adults at a large university-affiliated health system. METHODS: A retrospective, observational cohort study was conducted using electronic data from the Observational Health Data Sciences and Informatics database, assessing data from the University of Colorado Medical Campus and its affiliates. The outcome measured was the prevalence of dupilumab prescribed for adults with AD (n=6421), between March 28, 2013, and March 28, 2021. We assessed whether the characteristics of patients who received dupilumab were different from those who did not. Each patient characteristic was assessed using a univariate logistic regression with the binary outcome of receiving or not receiving dupilumab. RESULTS: We found a population prevalence of 5.6% (6421/114,476) for AD. In our cohort, Black patients with AD were more than twice as likely to have received dupilumab compared to White patients (odds ratio 2.352, 95% CI 1.58-3.39). Patients with a diagnosis of atopic neurodermatitis were approximately twice as likely to have received dupilumab compared to those with other diagnostic variants of AD (odds ratio 1.87, 95% CI 1.01-3.22). CONCLUSIONS: Our results demonstrate that both patient racial characteristics and specific AD diagnoses were associated with variations in dupilumab prescription patterns.

Isotretinoin Use in Transmasculine Patients and Its Implication on Chest Masculinization Surgery: Scoping Review of the Literature.

BACKGROUND: Acne often worsens in transmasculine patients who are on prolonged testosterone therapy. Isotretinoin is an oral retinoid used in the treatment of severe or refractory cases of acne, but it has the potential to cause delayed wound healing. Transmasculine patients may potentially be prescribed treatment for acne with isotretinoin while also planning to undergo chest masculinization surgery. OBJECTIVE: This scoping review aims to determine whether isotretinoin has a negative impact on postoperative healing in transmasculine patients undergoing chest masculinization surgery. METHODS: A scoping review was performed using the PubMed and Ovid databases. A total of 16 publications were selected for inclusion. RESULTS: Acne tends to peak in transmasculine patients 6 months after initiation of testosterone treatment. Severe cases can be treated with isotretinoin; however, acne may recur once treatment is discontinued, given ongoing hormone therapy. There is little to no evidence in the medical literature regarding perioperative use of isotretinoin specifically among transmasculine patients undergoing chest masculinization surgery. In general, however, recent studies have found no evidence of increased hypertrophic scars or keloids in patients taking isotretinoin. CONCLUSIONS: Further studies are required to strengthen the current evidence that suggests that isotretinoin does not need to be discontinued before or after incisional or excisional surgeries, including chest masculinization surgery in transmasculine patients.

Exploring the interactions of antihistamine with retinoic acid receptor beta (RARB) by molecular dynamics simulations and genome-wide meta-analysis.

Kaposi sarcoma (KS) is one of the most common AIDS-related malignant neoplasms, which can leave lesions on the skin among HIV patients. These lesions can be treated with 9-cis-retinoic acid (9-cis-RA), an endogenous ligand of retinoic acid receptors that has been FDA-approved for treatment of KS. However, topical application of 9-cis-RA can induce several unpleasant side effects, like headache, hyperlipidemia, and nausea. Hence, alternative therapeutics with less side effects are desirable. There are case reports associating over-the-counter antihistamine usage with regression of KS. Antihistamines competitively bind to H1 receptor and block the action of histamine, best known for being released in response to allergens. Furthermore, there are already dozens of antihistamines that are FDA-approved with less side effects than 9-cis-RA. This led our team to conduct a series of in-silico assays to determine whether antihistamines can activate retinoic acid receptors. First, we utilized high-throughput virtual screening and molecular dynamics simulations to model high-affinity interactions between antihistamines and retinoic acid receptor beta (RARß). We then performed systems genetics analysis to identify a genetic association between H1 receptor itself and molecular pathways involved in KS. Together, these findings advocate for exploration of antihistamines against KS, starting with our two promising hit compounds, bepotastine and hydroxyzine, for experimental validation study in the future.

Inflammatory Myofibroblastic Tumor of the Larynx: Report of a Case.

PURPOSE: Inflammatory myofibroblastic tumor (IMT) is a rare tumor composed of mesenchymal myofibroblastic spindle cells enveloped by an inflammatory infiltrate. Historically, this tumor sparked debate regarding whether it was a true malignancy with metastatic potential or merely a locally destructive physiologic inflammatory response. Few reports of IMT exist in the recent literature, with the majority of cases occurring in the pediatric population and favoring the lungs. Here we present an exceedingly rare case of IMT involving the larynx of a 22-year-old female. RESULTS: A hemorrhagic and solid mass of the right true membranous vocal fold was excised and sent for histopathological assessment. Features of the surgical specimens were diagnostic for IMT. Intralesional steroid therapy was selected for additional treatment. Panendoscopy facilitated surveillance for any additional or recurrent lesions, of which there were none. At 11 months post-excision, follow-up MRI revealed symmetric vocal cords without evidence of any masses. CONCLUSIONS: Although rare, laryngeal IMT should be considered in any patient presenting with hoarseness due to a vocal fold mass. Based on the successful treatment of our patient, we suggest that our approach of surgical excision followed by intralesional corticosteroid injection may be an efficacious treatment approach for this rare tumor. However, more research is warranted to elucidate the most effective, safe, and cost-effective treatment approach.

Gamification and Game-Based Strategies for Dermatology Education: Narrative Review.

BACKGROUND: Game-based approaches, or gamification, are popular learning strategies in medical education for health care providers and patients alike. Gamification has taken the form of serious educational games and simulations to enable learners to rehearse skills and knowledge in a safe environment. Dermatology learners in particular may benefit from gamification methods, given the visual and procedural nature of the field. OBJECTIVE: This narrative review surveys current applications of gamification within general medical training, in the education of dermatology students, and in dermatology patient outreach. METHODS: A literature search was performed using PubMed, Google Scholar, and ResearchGate to access and review relevant medical education- and dermatology-related gamification studies published in peer-reviewed journals. Two independent researchers with education and experience in dermatology screened publications to select studies featuring a diversity of gamification approaches and study subjects for in-depth examination. RESULTS: A total of 6 general medical education-related and 7 dermatology-specific gamification studies were selected. Gamification generally increased motivation and engagement, improved reinforcement of learning objectives, and contributed to more enjoyable and positive educational experiences compared to traditional modes of instruction. Enhancing examination scores, building confidence, and developing stronger team dynamics were additional benefits for medical trainees. Despite the abundance of gamification studies in general medical education, comparatively few instances were specific to dermatology learning, although large organizations such as the American Academy of Dermatology have begun to implement these strategies nationally. Gamification may also a provide promising alternative means of diversifying patient education and outreach methods, especially for self-identification of malignant melanoma. CONCLUSIONS: Serious games and simulations in general medical education have successfully increased learner motivation, enjoyment, and performance. In limited preliminary studies, gamified approaches to dermatology-specific medical education enhanced diagnostic accuracy and interest in the field. Game-based interventions in patient-focused educational pilot studies surrounding melanoma detection demonstrated similar efficacy and knowledge benefits. However, small study participant numbers and large variability in outcome measures may indicate decreased generalizability of findings regarding the current impact of gamification approaches, and further investigation in this area is warranted. Additionally, some relevant studies may have been omitted by the simplified literature search strategy of this narrative review. This could be expanded upon in a secondary systematic review of gamified educational platforms.