Variation of retinal and choroidal microvascularization after an exercise stress test in patients with effort angina.

PURPOSE: To describe retinal and choroidal vascular changes following an exercise stress test (ET) in patients with effort angina and to determine whether optical coherence tomography angiography (OCT-A) could play a role in the prediction of ischemic cardiac events. METHODS: Prospective comparative study including patients with effort angina. All patients underwent OCT-A before and after an ET was performed. Blood flow, intercapillary spaces, and vessel density were analyzed in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP). Vessel density in the choriocapillaris and the parameters of the central avascular zone (CAZ) were also analyzed. RESULTS: Of the 38 eyes included in the study, a decrease in blood flow was found in 39.5% in the large SCP vessels, in 50% in the capillaris of the SCP, and in 81.6% in the DCP. An increase in intercapillary spaces was observed in the SCP in 68.4% of eyes and in the DCP in 55.3% of eyes. A statistically significant decrease in the DCP density was observed after an ET (p = 0.03). There were no significant modifications in the CAZ parameters, the SCP density, nor the choriocapillaris density. Patients with a positive ET had a decreased DCP density in 83.3%. Among patients with an increased DCP density, 92.85% had a negatif ET. CONCLUSION: This pilot study suggests that DCP density significantly decreases after an ET. The DCP appears to be most affected in patients with effort angina. A larger trial is needed to further investigate these hypotheses.

Genomic landscape of liquid biopsy mutations in TP53 and DNA damage genes in cancer patients.

Next-generation sequencing (NGS) assays based on plasma cell-free DNA (cfDNA) are increasingly used for clinical trials inclusion. Their optimized limit of detection applied to a large number of genes leads to the identification of mutations not confirmed in tissue. It becomes essential to describe the characteristics and consequences of these liquid biopsy-only mutations. In the STING protocol (Gustave Roussy, NCT04932525), 542 patients with advanced solid cancer had cfDNA-based and tissue-based NGS analysis (performed by FoundationOne® Liquid CDx and FoundationOne CDx™, respectively). Mutations identified in the liquid biopsy but not in the paired tissue were considered as liquid biopsy-only mutations irrespective of their variant allelic frequency (VAF). Out of 542 patients, 281 (51.8%) harbored at least one liquid biopsy-only mutation. These patients were significantly older, and more heavily pretreated. Liquid biopsy-only mutations occurring in TP53, and in DDR genes (ATM, CHEK2, ATR, BRCA2, and BRCA1) accounted for 90.8% of all the mutations. The median VAF of these mutations was generally low (0.37% and 0.40% for TP53 and DDR genes respectively). The variant type repartition depended on the gene. Liquid biopsy-only mutations affected hotspot in TP53 codon 273, 125, 195, 176, 237 or 280 and ATM codon 2891 and 3008. In a subset of 37 patients, 75.0%, 53.5% and 83.3% of the liquid biopsy-only mutations occurring respectively in ATM, TP53, and CHEK2 were confirmed in the matching whole blood sample. Although liquid biopsy-only mutations makes the interpretation of liquid biopsy results more complex, they have distinct characteristics making them more easily identifiable.