Helana Ghali’s research while affiliated with University of South Florida and other places

Background Ten percent of patients with melanoma develop in-transit metastases (ITM). Isolated limb infusion (ILI) is a well-established therapy for unresectable ITM on the extremities, but the ideal sequencing/line of therapy of ILI has not been defined. This study evaluates ILI as first-line, second-line, or third or later-line therapy. Methods A retrospective review included all patients with unresectable ITM who underwent ILI from 2006-2023. Results A total of 130 patients were identified, 61% female, median age of 71 (31-89) years. Median follow-up was 37.5 months. ILI was first-line therapy in 80% (n = 104), second-line in 15% (n = 19), and third or later-line in 5.4% (n = 7). Overall response rate (ORR) and complete response (CR) rates for ILI as any line of therapy were 74% and 41%, respectively. ORR for ILI as first, second, or third or later-line therapy were 78%, 63%, and 57%, respectively. CR rates for ILI as first, second, or third or later-line therapy were 42%, 37%, and 43%, respectively. There were no significant differences in ORR, progression-free survival (PFS), overall survival, or disease-free survival between therapy lines. Median PFS for ILI as first, second, or third or later-line therapy were 6.9, 5.4, and 18 months, respectively. Conclusion Patients responded well to ILI, whether or not they received previous therapies for unresectable ITM. First-line ILI appears to have a better ORR than later lines of ILI. Although sample size limited statistical significance, there was a 21% improvement in ORR when ILI was used as first-line vs third-line therapy, which is clinically meaningful. ILI is effective for unresectable melanoma ITM and can be used as salvage therapy.

Dermatology remains highly competitive, with strong USMLE Step 1 scores traditionally crucial for securing residency positions. The 2023–2024 cycle introduced significant changes, including pass/fail USMLE Step 1 score reports and an expanded program signaling system. This study explores dermatology residency applicant profiles within this new context. A survey of 2023–2024 dermatology applicants was conducted via social media to gather demographic and application data. A total of 63 survey responses were collected: 74.6% matched and 25.4% unmatched. The racial distribution was 54% White/Caucasian, 25.4% Asian/Pacific Islander, 9.5% Black/African American, 4.8% Hispanic/Latino, and 6.3% other. The median USMLE Step 2 score was 257 (215–277). Racial differences in USMLE Step 2 scores were significant (P = 0.031), but did not affect match rates (P = 0.116). Letters of recommendation from dermatology program directors were linked to lower match rates (P = 0.036). A positive correlation was found between the number of audition rotations completed and matching at such programs (r²=0.817). Of all matched respondents, 46.8% matched to a program they did not signal; of these, 50.0% matched to a program at which they completed an audition rotation and 40.9% to their home dermatology program affiliation. The mean number of interviews was 8.02, with matched applicants receiving more invitations than unmatched applicants (9.02 vs. 5.06, P = 0.002). The shift to pass/fail USMLE Step 1 scores and expanded program signaling did not notably affect the median USMLE Step 2 score from prior years or match rates among underrepresented minorities. Success in matching continues to depend on a holistic evaluation.

Isolated limb infusion (ILI) treats unresectable extremity malignancies with high-dose regional chemotherapy limited to the limb. This study assessed long-term outcomes after ILI for limb-threatening sarcomas. A retrospective review analyzed patients with an extremity sarcoma who underwent ILI with melphalan and dactinomycin from 2008 to 2023 at a single institution. The study identified 61 patients (52.5% female; median age, 73 years; range, 20–94 years). Of these patients, 68.9% had lower-extremity disease. The median follow-up period was 6.9 years. The overall response rate was 48.3% (complete response [CR], 21.7%; partial response [PR], 26.7%), and the disease control rate (DCR: CR + PR + stable disease [SD]) was 65%. The median progression-free survival (PFS) for the patients with CR/PR/SD/progressive disease (PD) was respectively 16.8/9.6/4.8/2.4 months (P < 0.0001). The responders (CR + PR) had significantly longer PFS than the non-responders (SD + PD) (hazard ratio [HR], 6.3; 95% confidence interval [CI], 3.1–12.9; P < 0.001). The median in-field PFS times for CR/PR/SD/PD were respectively 16.8/12/4.8/2.4 months (P < 0.001). The responders had a significantly longer risk of in-field PFS than the non-responders (HR, 5.9; 95% CI 2.9–12.0; P < 0.001). The median distant relapse PFS for CR/PR/SD/PD was not reached (NR)/NR/44.4/40.8 months (P = 0.02). The responders had a significantly longer distant relapse PFS than the non-responders (HR, 2.7; range, 1.1–6.8; P = 0.04). The median overall survival (OS) was 8.6 years for the responders and 4.1 years for the non-responders (P = 0.02). The disease-specific survival (DSS) rates were 87% at 1 year, 71% at 3 years, and 64% at 5 years. The median DSS was not reached for the responders and was 4.1 years for the non-responders (P = 0.003). The limb salvage rates at 6 months were 85% at 1 year, 80% at 3 years, and 70% at 5 years. The patients with PD had a higher risk of requiring amputation than the patients with CR + PR + SD (HR, 3.0; 95% CI 1.0–8.7; P = 0.04). The 5-year limb salvage rates after ILI are notably high, reaching 70%. After ILI, the responders had significantly better in-field and distant relapse PFS, OS, and DSS.

Uveal melanoma often metastasizes to the liver, portending a poor prognosis. Melphalan/hepatic delivery system (HDS) via percutaneous hepatic perfusion (PHP) is a minimally invasive means of circulating high-dose chemotherapy through the affected liver. This study evaluated melphalan/HDS use as either first-line or second-line treatment to guide treatment sequencing. A retrospective review included patients with hepatic-dominant metastatic uveal melanoma who underwent melphalan/HDS treatment via PHP from 2008 to 2023. A total of 30 patients were identified; 53.3% female, with a median age of 63.5 years (37–78 years). Median follow-up time was 14.5 months. First-line therapies included melphalan/HDS (n = 17), liver-directed (n = 7), and immunotherapy (n = 6). Second-line therapies included melphalan/HDS (n = 6), immunotherapy (n = 5), and liver-directed (n = 3). Median hepatic progression-free survival (hPFS) for first-line melphalan/HDS, immunotherapy, and liver-directed therapy was 17.6/8.8/9.2 months, respectively (P = 0.002). Median hPFS for second-line melphalan/HDS, immunotherapy, and liver-directed therapy was not reached/14.7/7.5 months, respectively (P < 0.001). Median overall PFS for first-line melphalan/HDS, immunotherapy, and liver-directed therapy was 15.4/8.8/9.2 months, respectively (P = 0.04). Median overall PFS for second-line melphalan/HDS, immunotherapy, and liver-directed therapy was 22.2/14.7/7.5 months, respectively (P = 0.001). Melphalan/HDS via PHP for metastatic uveal melanoma to the liver was found to have significantly improved hPFS and overall PFS when used as first-line therapy compared with immunotherapy or liver-directed therapy. PHP continued to demonstrate improved hPFS and PFS when used as second-line therapy compared with second-line immunotherapy or liver-directed therapy.

N, N‐diethyl‐meta‐toluamide (DEET) has been considered the ‘gold standard’ for insect repellent use since the 1950s and constitutes most insect repellents on the market. However, conflicting data in the scientific literature and confusing information in the media are at the core of debates about the safety of DEET insect repellents for the protection of children against arthropod bites. The few fatal occurrences involving DEET insect repellents and complications of their use in the pediatric population are typically the result of accidental overdoses or misuse of insect repellents that disregard warnings on product labels. With appropriate application, the safety record of DEET insect repellents continues to be excellent with few side effects. The purpose of this review is to provide a summary of the literature on safety outcomes of DEET insect repellent use in children; outline the pediatric recommendations relating to DEET insect repellents; and provide an overview of EPA‐approved and naturally derived alternatives to DEET that possess low toxicity while providing a similar level of protection to synthetic insect repellents.