Distinctive lower incidence rates of cutaneous melanoma on the hips and lower extremities of men.

BACKGROUND: Cutaneous melanomas (CMs) are more frequently found on the trunk in men, and on the hip and lower extremities (legs) in women. This discrepancy has been attributed to greater exposure to ultraviolet (UV) radiation of women's legs due to their dressing habits. OBJECTIVES: To understand the sex difference in the bodily distribution of CMs, especially those on the legs. METHODS: This was a cancer registry-based cohort study. CM incidences, relative tumour density and tumour mutational burdens (TMBs) were compared among different body sites in different sex and racial groups using the SEER (Surveillance, Epidemiology, and End Results) and TCGA SKCM (The Cancer Genome Atlas skin cutaneous melanoma) databases. RESULTS: White men had lower rates and lower relative tumour density (RTD) of CMs on their legs compared with the rest of their body sites, or compared with White women. Men classified by SEER into racial groups other than White did not show such a trend. White women had comparable RTDs among different body sites. The ratios between the 'White' and the 'other' groups were used to evaluate the approximate effect of sun exposure at different body sites, which further validated a distinct protective effect of men's legs in melanoma. TMB on leg melanomas was lower than on other sites in both sexes. CONCLUSIONS: The legs of both sexes in White patients show lower RTDs and lower levels of TMB, suggesting a weaker association with UV exposure. Furthermore, White men are especially protected against CM on their legs, suggesting an unknown intrinsic protective factor as compared with women.

Automation of Hematopoietic Cell Transplantation Outcomes Reporting Leads to Dramatic Reduction in Errors Reported to Real-World Data Registry.

Institutions that perform hematopoietic cell transplantation (HCT) are required by law to report standardized, structured data on transplantation outcomes. A key post-transplantation outcome is engraftment, the time between HCT infusion and reemergence of circulating neutrophils and platelets. At our center, we found that manual chart abstraction for engraftment data was highly error-prone. We developed a custom R/Shiny application that automatically calculates engraftment dates and displays them in an intuitive format to augment the manual chart review. Our hypothesis was that use of the application to assist with calculating and reporting engraftment dates would be associated with a decreased error rate. The study was conducted at a single tertiary care institution. The application was developed in a collaborative, multidisciplinary fashion by members of an embedded cellular therapy informatics team. Retrospective validation of the application's accuracy was conducted on all malignant HCTs from February 2016 to December 2020 (n = 198). Real-world use of the application was evaluated prospectively from April 2021 through April 2022 (n = 53). The Welch 2-sample t test was used to compare error rates preimplementation and postimplementation. Data were visualized using p charts, and standard special cause variation rules were applied. The accuracy of reported data postdeployment increased dramatically; the engraftment error rate decreased from 15% to 3.8% for neutrophils (P = .003) and from 28% to 1.9% for platelets (P < .001). This study demonstrates the effective deployment of a custom R/Shiny application that was associated with significantly reduced error rates in HCT engraftment reporting for operational, research, and regulatory purposes. Users reported subjective satisfaction with the application and that it addressed difficulties with the legacy manual process. Identifying and correcting erroneous data in engraftment reporting could lead to a more efficient and accurate nationwide assessment of transplantation success. Furthermore, we show that it is possible and practical for academic medical centers to create and support embedded informatics teams that can quickly build applications for clinical operations in a manner compliant with regulatory requirements.

Impact of MEK Inhibitor Therapy on Neurocognitive Functioning in NF1.

BACKGROUND AND OBJECTIVES: Neurofibromatosis type 1 (NF1)-associated cognitive impairments carry significant lifelong morbidity. The lack of targeted biologic treatments remains a significant unmet need. We examine changes in cognition in patients with NF1 in the first 48 weeks of mitogen-activated protein kinase inhibitor (MEKi) treatment. METHODS: Fifty-nine patients with NF1 aged 5-27 years on an MEKi clinical trial treating plexiform neurofibroma underwent pretreatment and follow-up cognitive assessments over 48 weeks of treatment. Performance tasks (Cogstate) and observer-reported functioning (BRIEF) were the primary outcomes. Group-level (paired t tests) and individual-level analyses (Reliable Change Index, RCI) were used. RESULTS: Analysis showed statistically significant improvements on BRIEF compared with baseline (24-week Behavioral Regulation Index: t (58) = 3.03, p = 0.004, d = 0.24; 48-week Metacognition Index: t (39) = 2.70, p = 0.01, d = 0.27). RCI indicated that more patients had clinically significant improvement at 48 weeks than expected by chance (χ2 = 11.95, p = 0.001, odds ratio [OR] = 6.3). Group-level analyses indicated stable performance on Cogstate (p > 0.05). RCI statistics showed high proportions of improved working memory (24-week χ2 = 8.36, p = 0.004, OR = 4.6, and 48-week χ2 = 9.34, p = 0.004, OR = 5.3) but not visual learning/memory. Patients with baseline impairments on BRIEF were more likely to show significant improvement than nonimpaired patients (24 weeks 46% vs 8%; χ2 = 9.54, p = 0.008, OR = 9.22; 48 weeks 63% vs 16%; χ2 = 7.50, p = 0.02, OR = 9.0). DISCUSSION: Our data show no evidence of neurotoxicity in 48 weeks of treatment with an MEKi and a potential clinical signal supporting future research of MEKi as a cognitive intervention.