Patient oriented research and mentoring program in pyoderma gangrenosum and wound care - Pyoderma Gangrenosum (PG) is a rare, chronic inflammatory skin disorder that presents with painful, debilitating ulcers, severely impacting quality of life and increasing mortality risks. Despite its burden, PG currently lacks FDA-approved treatments. The challenge of clinical trial advancement is compounded by recruitment issues and the difficulty of achieving complete ulcer closure, the standard primary endpoint for PG trials. The prolonged duration of trials, often lasting up to a year, hinders progress and discourages investment in novel treatments. To address these challenges, innovative approaches to clinical endpoints are critical. This research explores the potential of Gulliver's sign, a unique marker of PG healing, and non-invasive high- frequency ultrasound (HFUS) imaging as objective tools to track wound progression. Additionally, pain, a hallmark symptom of PG, is often overlooked. Our research aims to incorporate time to pain reduction as a secondary endpoint, emphasizing its significance in evaluating treatment efficacy and enhancing patient quality of life. Our research has the potential to accelerate therapeutic development, offering more effective and timely interventions for PG patients. The specific aims of the proposed research are: 1) Determine the time to the onset of Gulliver's sign, and its associated percent area reduction (PAR), and correlate with healing by 1 year and 2) Determine the time to achieve a 2-point decrease in pain intensity from treatment initiation, as measured by the numerical rating scale (NRS), to support the adoption of reduced pain as a clinical endpoint. For aim 1, we will employ Kaplan- Meier survival curves to assess the time to the appearance of Gulliver's sign and estimate the median time to its occurrence. Logistic regression will be used, with the appearance of Gulliver's sign within 16 weeks as the independent variable and healing at 1 year as the dependent variable, to assess sensitivity and specificity. For aim 2, we will assess time to a 2-point pain reduction with a 16-week cutoff to dichotomize the groups using a Kaplan-Meier survival curve. Sensitivity and specificity will be evaluated using logistic regression analysis. Multivariable logistic regression models will be used to adjust for treatment, wound size, and comorbidities. This K24 award will significantly enhance Dr. Ortega's ability to mentor the next generation of clinician- scientists in patient-oriented research (POR), with a focus on dermatology, wound care, and rare skin diseases. Mentees will be actively involved in every stage of the research process, gaining practical experience that will be essential for their career development. A key component of this mentorship will also be focused on developing grantsmanship skills, equipping mentees with the knowledge and experience needed to successfully write and submit competitive grant applications. By fostering a collaborative research environment, this project will not only advance scientific understanding of PG but also help cultivate the next generation of skilled clinician-scientists with a strong foundation in research and funding acquisition.
