Biomedical subjects

Stuart A Scott

Publications and source records attributed to Stuart A Scott.

3 recordsLinked to original sources

PubMed2026

Hemophagocytic Lymphohistiocytosis and Fibroblast Growth Factor 23 (FGF23)-Induced Hypophosphatemia.

Hypophosphatemia is a frequent complication of chimeric antigen receptor T-cell therapy. In this setting, hypophosphatemia has been previously associated with cytokine release syndrome. The mechanisms underlying this electrolyte derangement are not fully understood. Extracellular phosphate consumption by chimeric antigen receptor T cells was demonstrated in vitro, but inflammation is also thought to play a contributing role. We present a case of severe, refractory hypophosphatemia with renal phosphate wasting triggered by hemophagocytic lymphohistiocytosis in acute lymphoblastic leukemia. The diagnosis of phosphate wasting was made at the onset of leukemia and a clinical exacerbation occurred after chimeric antigen receptor T-cell therapy. Diagnostic workup revealed very high fibroblast growth factor 23 (FGF23) levels in the absence of recognized acquired or genetic causes of impaired FGF23 cleavage. This case suggests that inflammation associated with hemophagocytic lymphohistiocytosis may induce FGF23 as a potential mechanism for hypophosphatemia. In this context, we recommend evaluation of renal phosphate wasting and subsequently FGF23 in patients with persistent hypophosphatemia despite standard supplementation.

Humans↗

PubMed2025

Toward an integrated resource for pharmacogenomics (PGx): Survey findings from the genomic medicine communities.

PURPOSE: Pharmacogenomics (PGx) is a critical component of precision health care that aims to improve drug efficacy and reduce adverse events. Terminologies and standards have not always aligned between PGx and broader genomic medicine communities, which is a barrier to PGx implementation. An updated assessment of community barriers, needs, and perspectives is critical to enable more standardized terminologies and interpretation frameworks. METHODS: The Clinical Genome Resource's PGx Interpretation Committee (PGxIC, formerly referred to as the PGx Working Group, PGxWG) conducted 2 surveys targeting the PGx and genomic medicine communities (n = 508) to evaluate perspectives on PGx clinical validity and actionability frameworks, as well as other barriers to PGx implementation. Surveys were tailored toward self-reported familiarity with PGx. Data primarily consisted of free text, which were analyzed using qualitative content analysis methods. RESULTS: Survey responses indicated conflation of terminology across disciplines, including confusion around differing definitions of terms in PGx and non-PGx contexts. Data also indicated broad support for leveraging existing PGx guidelines and framework structures alongside the standardization of approaches and centralization of resources. CONCLUSION: These novel survey results demonstrate broad consensus on the importance of integrating PGx into clinical practice, including support for development of gene-drug response clinical validity and actionability frameworks aligned with Clinical Genome Resource's frameworks for gene-disease relationships.

Humans↗

PubMed2025

Discovery of ancestry-specific variants associated with clopidogrel response among Caribbean Hispanics.

High on-treatment platelet reactivity (HTPR) with clopidogrel predicts ischemic events in adults with coronary artery disease, and while HTPR varies by ethnicity, no genome-wide association study (GWAS) of clopidogrel response has been conducted in Caribbean Hispanics. This study aimed to identify genetic predictors of HTPR in a cohort of 511 Puerto Rican cardiovascular patients treated with clopidogrel, stratified by P2Y12 reaction units (PRU) into responders and non-responders (HTPR). Local ancestry inference (LAI) and traditional GWAS identified variants in the CYP2C19 region associated with HTPR, primarily in individuals with European ancestry. Three variants (OSBPL10 rs1376606, DERL3 rs5030613, RGS6 rs9323567) showed suggestive significance, and a variant in UNC5C was linked to increased HTPR risk. These findings highlight the unique genetic landscape of Caribbean Hispanics and challenge the significance of CYP2C19*2 in predicting clopidogrel response in patients with high non-European ancestry. Further studies are needed to replicate these results in other diverse cohorts.

Journal Article↗