ABSTRACT
GOALS: This study aims to address gaps in medical knowledge by determining whether adenoma detection rate (ADR) in average-risk screening patients aged 45 to 49 is equivalent to screening patients aged 50 to 54. BACKGROUND: Current guidelines recommend initiating colon cancer screening at age 45, yet our understanding of the effects of ADR in average-risk individuals among 45- to 49-year-olds is still limited. STUDY: A retrospective analysis was conducted on records of average-risk screening colonoscopies performed on patients aged 45 to 54 from January 2018 to August 2022. Exclusions were prior diagnoses of colorectal cancer or adenomatous polyps, inflammatory bowel disease, personal or family history of genetic cancer syndromes, incomplete colonoscopy, and inadequate bowel preparation. The primary outcome was ADR in the age 45 to 49 group compared with the age 50 to 54 group. RESULTS: Of the 3199 average-risk screening colonoscopies performed, 879 and 2116 patients were included in the age 45 to 49 and 50 to 54 groups, respectively. Both groups were predominantly female, White ethnicity, never smokers, and obese. ADR was found to be 27% in the age 45 to 49 group compared with 34% in the age 50 to 54 group (odds ratio 0.70, 90% CI: 0.60-0.83, P-value for equivalence=0.81 w/ margin 0.77 to 1.30). CONCLUSIONS: The study did not demonstrate equivalent ADR between the 2 age groups, with ADR being substantially lower in the age 45 to 49 group (27% vs. 34%). Despite this, the ADR in the 45 to 49 age range surpasses the established benchmark of 25%, supporting the decision to lower the screening age to 45 years. Ongoing national monitoring is essential to comprehensively evaluate the impact of these updated guidelines.
ABSTRACT
Immune checkpoint pathways active in Acute Myeloid Leukemia (AML) patients, especially during the course of remission induction chemotherapy, have not been well studied. Although dominant in mediating T cell dysfunction in cancer, it is now well-accepted that interruption of PD-1/PD-L1 axes alone does not always completely restore T cell function, indicating the involvement of additional negative regulatory pathways, such as TIM-3/Gal-9, in promoting T cell exhaustion.Here, we characterized these pathways in AML patients enrolled in a phase I dose escalation trial that combined Selinexor, a Selective Inhibitor of Nuclear Export (SINE), with high-dose cytarabine (HiDAC) and mitoxantrone (Mito) (NCT02573363) as induction therapy.To monitor changes in expression of immune checkpoint receptors, multi-parameter flow cytometry was performed on peripheral blood and bone marrow biopsy specimens at diagnosis and following induction therapy in 26 AML patients. Expression of CD47, PD-L1, PD-L2 and Gal9 was assessed on CD34+ AML blasts, as well as on CD34- cell populations. In parallel, we evaluated expression of inhibitory (PD1, CTLA4, LAG3, TIM-3) and stimulatory (CD28, ICOS, CD137, OX40, CD40L, HLA-DR) co-receptors on CD4+ and CD8+ T cell subsets.Compared to baseline, the frequency of Gal9+ CD34- cells was significantly higher in patients with treatment failure (TF) than in those in complete remission (CR), and this finding correlated with increased TIM-3 expression on marrow-resident T cells in TF patients. Moreover, when we measured the expression level of PD-1 and TIM-3 in bone marrow samples compared to peripheral blood, TIM-3 was significantly higher in BM specimens.Our results suggest that targeting the Gal9/Tim-3 axis could be effective in combination with induction chemotherapy to increase the likelihood of complete remission in AML patients.
