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.

Prioritising Cochrane reviews to be updated with health equity focus.

BACKGROUND: The prioritisation of updating published systematic reviews of interventions is vital to prevent research waste and ensure relevance to stakeholders. The consideration of health equity in reviews is also important to ensure interventions will not exacerbate the existing inequities of the disadvantaged if universally implemented. This study aimed to pilot a priority setting exercise based on systematic reviews of interventions published in the Cochrane Library, to identify and prioritise reviews to be updated with a focus on health equity. METHODS: We conducted a priority setting exercise with a group of 13 international stakeholders. We identified Cochrane reviews of interventions that showed a reduction in mortality, had at least one Summary of Findings table and that focused on one of 42 conditions with a high global burden of disease from the 2019 WHO Global Burden of Disease report. This included 21 conditions used as indicators of success of the United Nations Universal Health Coverage in attaining the Sustainable Development Goals. Stakeholders prioritised reviews that were relevant to disadvantaged populations, or to characteristics of potential disadvantage within the general population. RESULTS: After searching for Cochrane reviews of interventions within 42 conditions, we identified 359 reviews that assessed mortality and included at least one Summary of Findings table. These pertained to 29 of the 42 conditions; 13 priority conditions had no reviews with the outcome mortality. Reducing the list to only reviews showing a clinically important reduction in mortality left 33 reviews. Stakeholders ranked these reviews in order of priority to be updated with a focus on health equity. CONCLUSIONS: This project developed and implemented a methodology to set priorities for updating systematic reviews spanning multiple health topics with a health equity focus. It prioritised reviews that reduce overall mortality, are relevant to disadvantaged populations, and focus on conditions with a high global burden of disease. This approach to the prioritisation of systematic reviews of interventions that reduce mortality provides a template that can be extended to reducing morbidity, and the combination of mortality and morbidity as represented in Disability-Adjusted Life Years and Quality-Adjusted Life Years.

Dermatologic Research Potential of the Observational Health Data Sciences and Informatics (OHDSI) Network.

BACKGROUND: The Observational Health Data Sciences and Informatics (OHDSI) network enables access to billions of deidentified, standardized health records and built-in analytics software for observational health research, with numerous potential applications to dermatology. While the use of the OHDSI has increased steadily over the past several years, review of the literature reveals few studies utilizing OHDSI in dermatology. To our knowledge, the University of Colorado School of Medicine is unique in its use of OHDSI for dermatology big data research. SUMMARY: A PubMed search was conducted in August 2020, followed by a literature review, with 24 of the 72 screened articles selected for inclusion. In this review, we discuss the ways OHDSI has been used to compile and analyze data, improve prediction and estimation capabilities, and inform treatment guidelines across specialties. We also discuss the potential for OHDSI in dermatology - specifically, ways that it could reveal adherence to available guidelines, establish standardized protocols, and ensure health equity. Key Messages: OHDSI has demonstrated broad utility in medicine. Adoption of OHDSI by the field of dermatology would facilitate big data research, allow for examination of current prescribing and treatment patterns without clear best practice guidelines, improve the dermatologic knowledge base and, by extension, improve patient outcomes.

Interferon and Toll-Like Receptor 7 Response in COVID-19: Implications of Topical Imiquimod for Prophylaxis and Treatment.

BACKGROUND: The innate immune system is recognized as an essential aspect of COVID-19 pathogenesis. Toll-like receptors (TLRs) are important in inducing antiviral response, triggering downstream production of interferons (IFNs). Certain loss-of-function variants in TLR7 are associated with increased COVID-19 disease severity, and imiquimod (ImiQ) is known to have immunomodulating effects as an agonist of TLR7. Given that topical imiquimod (topImiQ) is indicated for various dermatologic conditions, it is necessary for dermatologists to understand the interplay between innate immunity mechanisms and the potential role of ImiQ in COVID-19, with a particular focus on TLR7. SUMMARY: Our objective was to survey recent peer-reviewed scientific literature in the PubMed database, examine relevant evidence, and elucidate the relationships between IFNs, TLR7, the innate immune system, and topImiQ in the context of COVID-19. Despite limited studies on this topic, current evidence supports the critical role of TLRs in mounting a strong immune response against COVID-19. Of particular interest to dermatologists, topImiQ can result in systemic upregulation of the immune system via activation of TLR7. Key Message: Given the role of TLR7 in the systemic activation of the immune system, ImiQ, as a ligand of the TLR7 receptor, may have potential therapeutic benefit as a topical immunomodulatory treatment for COVID-19.

Long-term patient-related outcome measures of septoplasty: a systematic review.

PURPOSE: Septoplasty is a common rhinological procedure intended to relieve symptoms of chronic nasal obstruction. However, there remains a question as to whether patients obtain symptom improvement and are satisfied with surgical outcomes in the months and years after septoplasty. This review aims to evaluate the long-term efficacy of functional septoplasty for nasal septal deviation. METHODS: A systematic review of the literature was conducted from November 2014 to March 2016 using the Cochrane, EMBASE, and PubMed databases. Prospective trials concerning functional septoplasty, which assessed subjective outcomes and included long-term follow-up data (≥ 9 month post-septoplasty) were included. RESULTS: 2189 articles were screened with seven meeting the criteria for inclusion. Patient satisfaction was assessed in six studies, with rates of satisfaction provided in three of these, ranging from 69 to 100%. Two studies assessed the degree of patient satisfaction, with one study indicating that 88% of patients were moderately satisfied or better at 1 year post-op, and the other reporting that 50% of patients were satisfied. In assessing symptom relief, several methods were used, including validated questionnaires, with varying degrees of improvement in nasal obstruction reported. CONCLUSIONS: Septoplasty appears to be a far from perfect treatment for nasal obstruction due to septal deviation. However, given the heterogeneity of data and lack of randomized controlled trials (RCTs), future RCTs and use of validated questionnaires would enable generation of superior levels of evidence. We suggest future prospective trials evaluating prognostic factors in septoplasty, to better inform patients and facilitate the development of guidelines for surgical intervention.