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: As nationwide government-led whole-genome sequencing (WGS) projects progress, optimizing the clinical integration of large-scale WGS results is crucial. We explored how the initial analysis from Korea’s First WGS Pilot Study for Rare Diseases was applied in clinical practice, and then we reanalyzed the data comprehensively at Samsung Medical Center (SMC) Seoul, Korea. Methods: A prospective cohort study designed to collect WGS data under a Korean national initiative was conducted from August 2020 to December 2021. We focused on patients with rare diseases recruited from 16 university hospitals. The participants included 5,000 individuals (2,200 probands and 2,800 family members). The initial WGS data and diagnostic reference reports (from 682 probands and 484 family members), generated based on the First Korean WGS Pilot Study for Rare Diseases, were subsequently reanalyzed by SMC. Results: The initial analysis of the First Korean WGS Pilot Study data revealed a diagnostic rate of 17%. Upon receiving these results, the SMC conducted two rounds of reanalysis, increasing the diagnostic rate from 15% in the first analysis, to 18% in the second, and finally to 24% in the third (P = 1.6 × 10 −5 ). Key factors in improving the genetic diagnosis included increased detection of novel (likely) pathogenic variants (P = 1.0 × 10 −4 ), improved diagnostic rates with larger family recruitment (P = 0.004), and refined clinical information for more precise genotype–phenotype correlation analysis (40%). Conclusions Although national WGS projects lay a foundation for rare disease diagnosis, hospital-level reanalysis and multidisciplinary collaborations are crucial for optimizing diagnostic outcomes.

Venous thromboembolism (VTE), which includes pulmonary embolism and deep vein thrombosis, is a condition characterized by abnormal blood clot formation in the pulmonary arteries and the deep venous vasculature. It is often serious and sometimes even fatal if not promptly and appropriately treated. Moreover, the later consequences of VTE may result in reduced quality of life. The treatment of VTE depends on various factors, including the type, cause, and patient comorbidities. Furthermore, bleeding may occur as a side effect of VTE treatment. Thus, it is necessary to carefully weigh the benefits versus the risks of VTE treatment and to actively monitor patients undergoing treatment. Asian populations are known to have lower VTE incidences than Western populations, but recent studies have shown an increase in the incidence of VTE in Asia. A variety of treatment options are currently available owing to the introduction of direct oral anticoagulants.The current VTE treatment recommendation is based on evidence from previous studies, but it should be applied with careful consideration of the racial, genetic, and social characteristics in the Korean population.

BACKGROUND: Antimicrobial resistance (AMR) is an issue not only with regard to public health, but also in terms of economic impact. AMR surveillance has mainly been carried out in general hospitals, and not in nursing hospitals. This study was conducted to investigate the AMR rate for bacterial strains isolated from nursing hospital samples.METHODS: Antimicrobial susceptibility testing (AST) results from a total of 23,518 bacterial isolates recovered from clinical specimens taken in 61 nursing hosals were analyzed. AST was conducted using Vitek 2 with AST cards specific for the bacterial strains.RESULTS: A total of 19,357 Gram-negative and 4,161 Gram-positive bacterial strains were isolated. Pseudomonas aeruginosa (n=6,384) and Escherichia coli (n=5,468) were the most prevalent bacterial species and, among Gram-positive bacteria, Staphylococcus aureus (n=1,565) was common. The AMR rate was high for the following strains: cefotaxime-resistant Klebsiella pneumoniae, 77.4%; cefotaxime-resistant E. coli, 70.6%; imipenem-resistant Acinetobacter baumannii, 90.3%; imipenem-resistant P. aeruginosa, 49.3%; oxacillin-resistant S. aureus, 81.1%, penicillin-resistant Enterococcus faecalis, 44.8%, and vancomycin-resistant Enterococcus faecium, 53.5%. AMR rate change varied by bacterial species and antimicrobial drug.CONCLUSION: AMR rates of major pathogens from nursing hospitals were higher than those from general hospitals with the exception of imipenem-resistant A. baumannii. Continuous monitoring and infection control strategies are needed.
Acinetobacter baumannii ; Enterococcus faecalis ; Enterococcus faecium ; Escherichia coli ; Gram-Positive Bacteria ; Hospitals, General ; Infection Control ; Klebsiella pneumoniae ; Nursing ; Pseudomonas aeruginosa ; Public Health ; Staphylococcus aureus

BACKGROUND: Thromboelastography (TEG) provides comprehensive information on the whole blood clot formation phases, whereas thrombin generation assay (TGA) reveals the endogenous thrombin levels in plasma. We investigated the potential significance of TEG and TGA parameters for prediction of clinical bleeding in hematologic patients on the basis of the patient's platelet levels. METHODS: TEG and TGA were performed in 126 patients with thrombocytopenia or hematologic malignancies. The bleeding tendencies were stratified on the basis of the World Health Organization bleeding grade. RESULTS: Maximum amplitude (MA) and clot formation in TEG and endogenous thrombin potential (ETP) in TGA showed significant associations with high bleeding grades (P=0.001 and P=0.011, respectively). In patients with platelet counts ≤10×10⁹/L, low MA values were strongly associated with a high bleeding risk. For bleeding prediction, the area under the curve (AUC) of MA (0.857) and ETP (0.809) in patients with severe thrombocytopenia tended to be higher than that of platelets (0.740) in all patients. Patients with platelet counts ≤10×10⁹/L displayed the highest AUC of the combined MA and ETP (0.929). CONCLUSIONS: Both TEG and TGA were considered to be good predictors of clinical bleeding in patients with severe thrombocytopenia. Combination of the ETP and MA values resulted in a more sensitive bleeding risk prediction in those with severe thrombocytopenia.
Area Under Curve ; Blood Platelets ; Hematologic Neoplasms* ; Hemorrhage* ; Humans ; Plasma ; Platelet Count ; Thrombelastography* ; Thrombin* ; Thrombocytopenia* ; World Health Organization

The aim of this study was to determine the prevalence of attention deficit hyperactivity disorders (ADHD) in children according to socio-demographic factors and the distribution of ADHD subtypes in a community in Korea. A screening survey using the Korean version of ADHD Rating Scale (K-ARS) was conducted between 2007 and 2008, and clinical interviews by a pediatric psychiatrist were performed for selected children between 2009 and 2010. A total of 49,573 elementary school students, between ages of 7 and 12, constituted the target population, among which 38,365 students (77.2%) and respective parents gave consent to participate. Of the participants, 200 screened children were clinically examined to confirm the diagnosis of ADHD. We estimated the prevalence of ADHD and its comorbidity in the population, after adjusting for nonresponse and nonparticipation. The prevalence of ADHD was 11.7% in boys and 5.2% in girls, with an overall prevalence of 8.5%. The combined type of inattentive and hyperactive was the most frequent at 4.7% of the whole population. Children were more likely to have ADHD if their parents were separated and had less education. Most commonly combined comorbidity was autism spectrum disorder (ASD) (10.1%). The prevalence of ADHD in the school-aged population is an essential information for improving the quality of public health mental services for evaluation and treatment of ADHD.
Attention Deficit Disorder with Hyperactivity ; Autism Spectrum Disorder ; Child* ; Comorbidity* ; Diagnosis ; Education ; Female ; Health Services Needs and Demand ; Humans ; Korea ; Mass Screening ; Parents ; Prevalence* ; Psychiatry ; Public Health

In 2010, we proposed the first Korean Guidelines for the Prevention of Venous Thromboembolism (VTE). It was applicable to Korean patients, by modifying the contents of the second edition of the Japanese guidelines for the prevention of VTE and the 8th edition of the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines. From 2007 to 2011, we conducted a nationwide study regarding the incidence of VTE after major surgery using the Health Insurance Review and Assessment Service (HIRA) database. In addition, we have considered the 9th edition of the ACCP Evidenced-Based Clinical Practice Guidelines, published in 2012. It emphasized the importance of clinically relevant events as opposed to asymptomatic outcomes with preferences for both thrombotic and bleeding outcomes. Thus, in the development of the new Korean guidelines, three major points were addressed: 1) the new guidelines stratify patients into 4 risk groups (very low, low, moderate, and high) according to the actual incidence of symptomatic VTE from the HIRA databases; 2) the recommended optimal VTE prophylaxis for each group was modified according to condition-specific thrombotic and bleeding risks; 3) guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and/or physician advice.
Age Factors ; Anticoagulants/adverse effects/*therapeutic use ; Asian Continental Ancestry Group ; Evidence-Based Medicine ; Heparin, Low-Molecular-Weight/therapeutic use ; Humans ; *Mechanical Thrombolysis ; Neoplasms/complications/surgery ; Republic of Korea ; Risk Assessment ; Surgical Procedures, Operative/adverse effects ; Venous Thromboembolism/etiology/prevention & control/*therapy

PURPOSE: Sensitization to allergens is considered as major mechanism of allergy and related to the development of allergic diseases. The objective of this study was to evaluate overall sensitization rates of inhalant allergens and the relationship between polysensitization and prevalence of allergic diseases in children and adolescents. METHODS: A cross-sectional pilot study of 122 elementary school students, 114 middle school students, and 115 high school students from Incheon and Asan was conducted by using the International Study of Asthma and Allergies in Childhood (ISSAC) questionnaire. The skin prick tests were performed with 14 common inhalant allergens on 339 students. RESULTS: The inhalant allergen that has a significantly different sensitization rate according to age was Dermatophagoides farinae. And the inhalant allergen that has significantly different sensitization rate according to region was Japanese hop. In addition, girls have higher sensitization rate to any mold allergens than boys. In case of having sensitization more than two allergens, the risks of diagnosis of asthma and allergic rhinitis on questionnaire were increased. Asthma is related to sensitization of dog or cat and allergic rhinitis is related to sensitization of house dust mites. However, atopic dermatitis is not related to sensitization of any inhalant allergens. CONCLUSION: The sensitization rates of inhalant allergens may differ among age, gender, and region in children and adolescents of Incheon and Asan area. The polysensitized children and adolescents with inhalant allergens showed higher prevalences of allergic diseases such as asthma and allergic rhinitis on questionnaire than monosensitized group.
Adolescent ; Allergens ; Animals ; Asian Continental Ancestry Group ; Asthma ; Cats ; Child ; Dermatitis, Atopic ; Dermatophagoides farinae ; Dogs ; Fungi ; Humans ; Humulus ; Hypersensitivity ; Pilot Projects ; Prevalence ; Pyroglyphidae ; Rhinitis ; Rhinitis, Allergic, Perennial ; Skin ; Surveys and Questionnaires

Platelet membrane receptor glycoproteins (GP) are essential for the platelet activation process, and the genetic polymorphisms in the genes that encode platelet glycoproteins have been proposed to influence the risk of acute coronary syndrome and atherosclerosis. In this study, we investigated the role of GPIa, HPA-1 and HPA-3 polymorphisms as putative risk factors for myocardial infarction (MI) and the extent of coronary artery disease. We selected 1, 073 subjects who underwent coronary angiography; 242 had normal or minimal coronary atherosclerosis, and 831 patients had significant coronary artery disease (CAD). The genotype was determined by the methods of single base extension for C807T/G873A polymorphisms of GPIa, and restriction fragment length polymorphism for HPA-1 and HPA-3. The C807T and G873A polymorphisms of GPIa showed complete linkage in the Korean population. For HPA-1 gene polymorphism, only the HPA-1a/a (PlA1/A1) genotype was observed in 192 selected subjects from our study population. The distribution of GPIa (C807T/G873A) and HPA-3 genotypes did not differ significantly between normal subjects and CAD subjects. No significant association between MI and both gene polymorphisms was present. However, for the subgroup analysis of young male patients whose age was less than 56 years, the genotype frequency of HPA-3b/b was significantly lower in patients with MI compared to patients without a history of MI (7.5% vs. 20.0%, p=0.04). The odds ratio for HPA-3 b homozygosity versus the HPA-3a carrier was 0.32 (95% CI, 0.10- 0.99, p=0.04). Conclusively, HPA-3 polymorphism was associated with MI in Korean individuals younger than 56 years of age, but other polymorphisms of GP, which we studied, were not associated with both the extent of coronary atherosclerosis or MI.
Aged ; Coronary Arteriosclerosis/epidemiology/*genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease/epidemiology ; Genotype ; Human ; Integrin alpha2/*genetics ; Integrin beta3/*genetics ; Korea ; Male ; Middle Aged ; Myocardial Infarction/epidemiology/*genetics ; Platelet Membrane Glycoprotein IIb/*genetics ; *Polymorphism (Genetics) ; Risk Factors ; Support, Non-U.S. Gov't