Physicians' Perspectives on HL7 Information Policy Sensitive Value Set: A Validation Study through Health Concept Categorization.

The Health Level 7 (HL7) organization introduced the Information Sensitivity Policy Value Set with 45 sensitive data categories to facilitate the implementation of granular electronic consent technology. The goal is to allow patients to have control over the sharing of their sensitive medical records. This study represents the first attempt to explore physicians' viewpoints on these categories. Twelve physicians participated in a survey, leading to revisions in 21 HL7 categories. They later classified 600 clinical data items through a second survey using the updated categories. Participants' perspectives were documented, and data analysis included descriptive measures and heat maps. In the first survey, six participants suggested adding 19 new categories (e.g., personality disorder), and modifying 25 category definitions. Two new categories and sixteen revised category definitions were incorporated to support more patient-friendly content and inclusive language. Fifteen new category recommendations were addressed through a revision of category definitions (e.g., personality disorder described as a behavioral health condition). In the second survey, data categorizations led to recommendations for more categories from ten participants. Future revisions of the HL7 categories should incorporate physicians' viewpoints, validate the categories using patient data or/and include patients' perspectives, and develop patient-centric category specifications.

ICOS and OX40 tandem co-stimulation enhances CAR T-cell cytotoxicity and promotes T-cell persistence phenotype.

Chimeric Antigen Receptor (CAR) T-cell therapies have emerged as an effective and potentially curative immunotherapy for patients with relapsed or refractory malignancies. Treatment with CD19 CAR T-cells has shown unprecedented results in hematological malignancies, including heavily refractory leukemia, lymphoma, and myeloma cases. Despite these encouraging results, CAR T-cell therapy faces limitations, including the lack of long-term responses in nearly 50-70% of the treated patients and low efficacy in solid tumors. Among other reasons, these restrictions are related to the lack of targetable tumor-associated antigens, limitations on the CAR design and interactions with the tumor microenvironment (TME), as well as short-term CAR T-cell persistence. Because of these reasons, we developed and tested a chimeric antigen receptor (CAR) construct with an anti-ROR1 single-chain variable-fragment cassette connected to CD3ζ by second and third-generation intracellular signaling domains including 4-1BB, CD28/4-1BB, ICOS/4-1BB or ICOS/OX40. We observed that after several successive tumor-cell in vitro challenges, ROR1.ICOS.OX40ζ continued to proliferate, produce pro-inflammatory cytokines, and induce cytotoxicity against ROR1+ cell lines in vitro with enhanced potency. Additionally, in vivo ROR1.ICOS.OX40ζ T-cells showed anti-lymphoma activity, a long-lasting central memory phenotype, improved overall survival, and evidence of long-term CAR T-cell persistence. We conclude that anti-ROR1 CAR T-cells that are activated by ICOS.OX40 tandem co-stimulation show in vitro and in vivo enhanced targeted cytotoxicity associated with a phenotype that promotes T-cell persistence.