Background: Older patients aged ≥75 years are underrepresented in major statin trials, leaving the optimal statin intensity after acute ischemic stroke (AIS) undefined. We aimed to compare functional outcomes and short-term safety between high-intensity statin therapy (HIST) and moderate-intensity statin therapy (MIST) in patients aged ≥75 years with AIS or transient ischemic attack. Methods: Using a prospective stroke registry at a single tertiary center (2019–2022), we retrospectively analyzed 337 patients aged ≥75 years with AIS or transient ischemic attack who maintained statin therapy for 3 months (HIST n=117; MIST n=220). The primary outcome was a favorable 3-month functional outcome (modified Rankin Scale score 0–2). Secondary outcomes included stroke recurrence, adverse effects, and statin discontinuation. Multivariable logistic regression with pre-specified sensitivity analyses was performed. Results: Favorable outcomes at 3 months were more frequent with HIST (70.9% vs. 55.9%; p=0.010). After multivariable adjustment, HIST was independently associated with a favorable outcome (adjusted odds ratio [aOR]=2.03, 95% confidence interval [CI] 1.17–3.53), consistent across sensitivity analyses: per-protocol (aOR=3.48, 95% CI 1.97–6.17) and atrial fibrillation-adjusted (aOR=2.21, 95% CI 1.26–3.89). No significant differences were observed in statin discontinuation, stroke recurrence, or adverse effects. Conclusion In older patients with AIS, HIST was independently associated with better functional outcomes without evidence of increased harm, broadly consistent with current guideline recommendations for HIST when tolerated. Prospective studies are needed to confirm a causal relationship.

Bacillus Calmette-Guérin (BCG) serves as an anticancer drug for bladder cancer by enhancing the innate immune response and facilitating the expression of beta-defensin-2/-3. BCG is significantly more effective than other treatment modalities; however, it has limitations due to the nonspecific secretion of immune proteins such as interleukin-2 (IL-2) and IFN-γ, necessitating frequent injections that result in toxicity. The newly developed BCG-cell wall skeleton (BCG-CWS) is intended to address the non-specificity and the requirement for repeated treatments associated with BCG. BCG-CWS stimulates antigen-presenting cells by secreting cytokines such as IL-12, using an adjuvant to enhance the immune response and synergize with it to provoke a potent immune reaction. Nevertheless, BCG-CWS encounters issues related to cellular uptake due to the substantial molecular weight of the drug.To meet this challenge, various strategies such as the introduction of R8 protein, the liposome evaporated via an emulsified lipid method, and nanoparticle formulation have been employed which can enhance targeted drug delivery, though issues related to particle size remain unresolved. This paper aims to discuss future perspectives by examining the mechanisms and challenges of BCG-CWS.

Bacillus Calmette-Guérin (BCG) serves as an anticancer drug for bladder cancer by enhancing the innate immune response and facilitating the expression of beta-defensin-2/-3. BCG is significantly more effective than other treatment modalities; however, it has limitations due to the nonspecific secretion of immune proteins such as interleukin-2 (IL-2) and IFN-γ, necessitating frequent injections that result in toxicity. The newly developed BCG-cell wall skeleton (BCG-CWS) is intended to address the non-specificity and the requirement for repeated treatments associated with BCG. BCG-CWS stimulates antigen-presenting cells by secreting cytokines such as IL-12, using an adjuvant to enhance the immune response and synergize with it to provoke a potent immune reaction. Nevertheless, BCG-CWS encounters issues related to cellular uptake due to the substantial molecular weight of the drug.To meet this challenge, various strategies such as the introduction of R8 protein, the liposome evaporated via an emulsified lipid method, and nanoparticle formulation have been employed which can enhance targeted drug delivery, though issues related to particle size remain unresolved. This paper aims to discuss future perspectives by examining the mechanisms and challenges of BCG-CWS.

Bacillus Calmette-Guérin (BCG) serves as an anticancer drug for bladder cancer by enhancing the innate immune response and facilitating the expression of beta-defensin-2/-3. BCG is significantly more effective than other treatment modalities; however, it has limitations due to the nonspecific secretion of immune proteins such as interleukin-2 (IL-2) and IFN-γ, necessitating frequent injections that result in toxicity. The newly developed BCG-cell wall skeleton (BCG-CWS) is intended to address the non-specificity and the requirement for repeated treatments associated with BCG. BCG-CWS stimulates antigen-presenting cells by secreting cytokines such as IL-12, using an adjuvant to enhance the immune response and synergize with it to provoke a potent immune reaction. Nevertheless, BCG-CWS encounters issues related to cellular uptake due to the substantial molecular weight of the drug.To meet this challenge, various strategies such as the introduction of R8 protein, the liposome evaporated via an emulsified lipid method, and nanoparticle formulation have been employed which can enhance targeted drug delivery, though issues related to particle size remain unresolved. This paper aims to discuss future perspectives by examining the mechanisms and challenges of BCG-CWS.

Background: TP53 mutations are associated with poor prognosis in myelodysplastic neoplasm (MDS) and AML. The updated 5th WHO classification and International Consensus Classification (ICC) categorize TP53-mutated MDS and AML as unique entities. We conducted a multicenter study in Korea to investigate the characteristics of TP53-mutated MDS and AML, focusing on diagnostic aspects based on updated classifications. Methods: This study included patients aged ≥ 18 yrs who were diagnosed as having MDS(N = 1,244) or AML (N = 2,115) at six institutions. The results of bone marrow examination, cytogenetic studies, and targeted next-generation sequencing, including TP53, were collected and analyzed. Results: TP53 mutations were detected in 9.3% and 9.2% of patients with MDS and AML, respectively. Missense mutation was the most common, with hotspot codons R248/ R273/G245/Y220/R175/C238 accounting for 25.4% of TP53 mutations. Ten percent of patients had multiple TP53 mutations, and 78.4% had a complex karyotype. The median variant allele frequency (VAF) of TP53 mutations was 41.5%, with a notable difference according to the presence of a complex karyotype. According to the 5th WHO classification and ICC, the multi-hit TP53 mutation criteria were met in 58.6% and 75% of MDS patients, respectively, and the primary determinants were a TP53 VAF > 50% for the 5th WHO classification and the presence of a complex karyotype for the ICC. Conclusions Collectively, we elucidated the molecular genetic characteristics of patients with TP53-mutated MDS and AML, highlighting key factors in applying TP53 mutation-related criteria in updated classifications, which will aid in establishing diagnostic strategies.

Purpose: Apixaban is recommended for patients with atrial fibrillation. Although routine monitoring of plasma concentrations is not typically advised, factors such as ethnicity, sex, and comorbidities can influence these levels. Our study analyzed the plasma apixaban concentrations (PAC) in patients to explore whether these levels, along with underlying conditions, offer enhanced insights for risk stratification. Methods: This study analyzed 49 patients with atrial fibrillation who had been taking apixaban for over a month, examined factor Xa levels within 6 h post-administration, and correlated PAC with clinical characteristics such as age, body weight, estimated glomerular filtration rate (eGFR), presence of heart failure, and bleeding events. Results: The mean plasma concentration of apixaban in all patients was 160.3 ± 77.5 ng/mL. Those taking apixaban 5 mg twice daily had higher plasma concentrations than those taking 2.5 mg twice daily (191.2 ± 75.3 ng/mL vs.137.2 ± 72.0 ng/mL, p = 0.014). Among the patients receiving a reduced dose, renal function and heart failure were significantly associated with plasma concentrations. No factors were associated with the plasma concentrations in patients receiving the standard dose. Notably, reduced-dose patients with heart failure had plasma concentrations comparable to those of individuals receiving the standard dose and exhibited a higher incidence of bleeding than the other groups. Conclusions PAC measurement revealed that apixaban dosages, classified based on age, body weight, and eGFR, were generally effective. Nonetheless, heart failure may increase plasma levels and correlate with an increased bleeding risk in Korean patients on reduced doses. Therefore, tailoring apixaban prescriptions to account for heart failure and other comorbidities may enhance treatment efficacy.

Background: Flow cytometric immunophenotyping of hematolymphoid neoplasms (FCIHLN) is essential for diagnosis, classification, and minimal residual disease (MRD) monitoring. FCI-HLN is typically performed using in-house protocols, raising the need for standardization. Therefore, we surveyed the current status of FCI-HLN in Korea to obtain fundamental data for quality improvement and standardization. Methods: Eight university hospitals actively conducting FCI-HLN participated in our survey.We analyzed responses to a questionnaire that included inquiries regarding test items, reagent antibodies (RAs), fluorophores, sample amounts (SAs), reagent antibody amounts (RAAs), acquisition cell number (ACN), isotype control (IC) usage, positiveegative criteria, and reporting. Results: Most hospitals used acute HLN, chronic HLN, plasma cell neoplasm (PCN), and MRD panels. The numbers of RAs were heterogeneous, with a maximum of 32, 26, 12, 14, and 10 antibodies used for acute HLN, chronic HLN, PCN, ALL-MRD, and multiple myeloma-MRD, respectively. The number of fluorophores ranged from 4 to 10. RAs, SAs, RAAs, and ACN were diverse. Most hospitals used a positive criterion of 20%, whereas one used 10% for acute and chronic HLN panels. Five hospitals used ICs for the negative criterion. Positiveegative assignments, percentages, and general opinions were commonly reported. In MRD reporting, the limit of detection and lower limit of quantification were included. Conclusions This is the first comprehensive study on the current status of FCI-HLN in Korea, confirming the high heterogeneity and complexity of FCI-HLN practices. Standardization of FCI-HLN is urgently needed. The findings provide a reference for establishing standard FCI-HLN guidelines.

Primary aldosteronism is a group of disorders in which the autonomous secretion of aldosterone is associated with hypertension and hypokalemia. It is crucial to determine the laterality of aldosterone hypersecretion because treatment options differ accordingly. Adrenal venous sampling (AVS) is considered the most reliable method for assessing the laterality of primary aldosteronism. This procedure is often technically challenging because of the small size and varied locations of the adrenal veins. A better understanding of anatomical variations and careful review of imaging studies would improve sampling success. This report presents three cases of anatomical variations encountered during AVS.

Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety. We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles. Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology clinical trials (IIPOCTs), which later guided sponsor-initiated precision oncology clinical trials (SIPOCTs). Most SIPOCTs were international studies with basket design. IIPOCTs primarily used the central laboratory for biomarker screening, but SIPOCTs used both central and local laboratories. Most of the studies adapted next-generation sequencing and/or immunohistochemistry for biomarker screening. Fifteen studies included an independent central review committee for outcome investigation. Efficacy assessments predominantly featured objective response rate as the primary endpoint, with varying results. Nine eligible studies contributed to the United States Food and Drug Administration’s marketing authorization. Safety monitoring was rigorous, but reporting formats lacked uniformity. Health-related quality of life and patient-reported outcomes were described in some protocols but rarely reported. Our results reveal that precision oncology trials with adaptive design rapidly and efficiently evaluate anticancer drugs’ efficacy and safety, particularly in specified biomarker-driven cohorts. The evolution from IIPOCT to SIPOCT has facilitated fast regulatory approval, providing valuable insights into the precision oncology landscape.

Objective: Since the impact of the coronavirus disease-2019 pandemic, the need for efficiency in medical services has become more urgent than ever. The digital treatment market is rapidly growing worldwide and digital therapeutics (DTx), a major part of the digital medical services, is also emerging as a new paradigm for treatment, with its industry growing rapidly as well. Increasing research is done on the effectiveness of mobile DTx in improving mental health conditions such as insomnia, panic, and depression. Methods: This review paper investigates 1) the functions and characteristics of mobile digital mental health care applications for the treatment of anxiety symptoms, 2) extracts common attributes of the applications, and 3) compares them with existing traditional treatment mechanisms. Results: Among the 20,000 mental health management applications that have been developed so far, 8 applications that are relatively widely used were selected and reviewed. Check-in, self-help tips, quick relief, journal, courses for practice are common features of the digital mental health care applications for anxiety and are also widely used feature in the cognitive behavioral therapy. Conclusion Based on this review, we have proposed the essential elements and directions for the development of a Korean digital mental health care applications for anxiety disorders.