Purpose: While TP53 mutations are well known to be associated with adverse prognosis in hematological diseases, their functional impact remains incompletely understood. This study examines the spectrum of TP53 mutations across various hematologic malignancies and evaluates their functional impact. Materials and Methods: Using targeted sequencing panels, we analyzed TP53 mutations in the bone marrow aspiration samples of a retrospective cohort of 856 patients diagnosed with hematologic malignancies. To assess the impact of TP53 mutations, we applied the evolutionary action (EAp53) score and the relative fitness score (RFS), previously proposed functional scoring methods. The effects of variant allele frequency (VAF), disruptive mutations, EAp53 score, and RFS on overall survival (OS) were evaluated. Results: TP53 mutations were associated with inferior OS compared with wildtype TP53 (median OS 10.0 months versus not estimable; hazard ratio (HR) 4.6; p<0.001). In the acute myeloid leukemia, multiple myeloma, and myelodysplastic syndrome subgroups, TP53 mutations had a significant adverse impact on OS. (HRs 3.8, 4.2, 6.0, respectively; p<0.001, p=0.005, p<0.001, respectively). Patients with VAF >50% had significantly poorer OS compared to those with VAF ≤50% (median OS 7.5 months versus 22.8 months; HR 2.2, p=0.016). Moreover, patients in the high-risk RFS group (RFS >0.22) had significantly worse OS compared to those in the low-risk RFS group (RFS ≤0.22) (median OS 5.6 months versus 16.3 months; HR 2.2, p=0.041). However, no significant survival difference was observed between the EAp53 high-risk (>75) and low-risk (≤75) groups, or between patients with disruptive and non-disruptive mutations. Conclusion Our findings highlight VAF and RFS as valuable tools for stratifying TP53-mutant patients into high-risk and low-risk groups.

Background: s/Aims: Calcium is a preventive factor for colorectal cancer, which develops from colorectal adenoma. This study aimed to investigate the association between dietary calcium intake and prevalence of colorectal adenoma among Korean adults. Methods: Overall, 612 participants aged ≥ 20 years who underwent gastrointestinal endoscopy at 8 medical centers from 2021 to 2023 were included. Dietary calcium intake was assessed using a food frequency questionnaire and was energy-adjusted using the residual model. Multivariate logistic regression models were used to calculate for the odds ratios (ORs) and 95% confidence intervals (CIs). The associations between dietary calcium intake and colorectal adenoma prevalence were also assessed according to the anatomic subsites and adenoma status (advanced or nonadvanced). Results: Among the 612 participants, 269 were diagnosed with colorectal adenoma (170 men and 99 women). With respect to the gender-specific association, low dietary calcium intake was associated with higher prevalence of colorectal adenoma among men (ORs [95% CIs]: 2.13 [0.50– 9.00] for < 250 mg/day; 3.53 [1.06–11.76], 250 to < 350 mg/day; and 1.84 [0.63–5.35], 350 to < 650 mg/day, compared to ≥ 650 mg/day of dietary calcium [p for trend = 0.07]). Similar association was observed among women, but neither the association nor trend was statistically significant (p for trend = 0.59). These inverse associations remained similar for distal colon/rectal adenoma among women and advanced adenoma among men. Conclusions Low dietary calcium intake was associated with high colorectal adenoma prevalence, particularly among men. Given the limited number of studies among Asian populations, our findings should be replicated in other Asian groups.

Background and Objectives: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a life-threatening inherited arrhythmogenic disorder. Recently, RYR2, the major CPVTcausative gene, was associated with neuropsychiatric manifestations. We aimed to analyze the clinical presentations, neuropsychiatric manifestations, and treatment outcomes of children with CPVT. Methods: We retrospectively reviewed 23 patients diagnosed with CPVT before 19 years of age. Genetic analysis, history of neuropsychiatric manifestations, changes in ventricular arrhythmia burden before and after treatment, occurrence of cardiac events, and overall survival (OS) were investigated. Results: RYR2 variants were identified in 17 patients, and 14 were classified as pathogenic or likely pathogenic. Neuropsychiatric manifestations, including intellectual disability and attention deficit hyperactivity disorder, were identified in 10 patients (43.5%). The 5-year cardiac event-free survival rate was 31.2%, and the 10-year OS rate was 73.1%. Patients diagnosed since 2009 had a higher cardiac event-free survival rate than those diagnosed before 2009 (p=0.0028).Combined beta-blocker and flecainide therapy demonstrated a lower risk of cardiac events than beta-blocker monotherapy (hazard ratio [HR], 0.08; 95% confidence interval [CI], 0.02–0.38;p=0.002). Left cardiac sympathetic denervation (LCSD) reduced the ventricular arrhythmia burden in Holter monitoring. Occurrence of near-fatal cardiac events after diagnosis was an independent predictor of death (HR, 33.40; 95% CI, 6.23–179.95; p<0.001). Conclusions Neuropsychiatric manifestations are common in children with CPVT. Flecainide and/or LCSD, when added to beta-blocker therapy, reduce the ventricular arrhythmia burden and cardiac events, thereby improving treatment outcomes in recent years.