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.

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.

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.

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.

Objectives: With the recent global mpox outbreak, the JYNNEOS vaccine (Modified VacciniaAnkara-Bavarian Nordic) was developed as a third-generation smallpox vaccine and initiallyfavored for mpox immunization. Vaccine-associated side effects contribute to vaccinehesitancy. Consequently, tracking adverse events post-immunization is crucial for safety management. This study used data from the national active vaccine safety surveillance conducted in Korea from August 25 to November 24, 2022 to detect potential safety signals and adverse events. Methods: Data on health conditions following vaccination were gathered from web-based surveys and reported via active surveillance through the Immunization Registry Information System. This follow-up system functioned via a text message link, surveying adverse events and health conditions beginning on the second day post-vaccination. Information aboutspecific adverse events, including both local and systemic reactions, was collected. Results: The study included 86 healthcare workers who had received at least 1 dose of the JYNNEOS vaccine. Among the respondents, 79.1% reported experiencing at least 1 adverse event, with the majority being local reactions at the injection site. The incidence of adverse events was higher following the first dose (67.9%) than after the second dose (34.4%). The most frequently reported adverse event for both doses was mild pain at the injection site. Conclusion The study provides crucial information on the safety of the JYNNEOS vaccine, demonstrating that most adverse events were manageable and predominantly localized to the injection site. Nonetheless, additional research is needed on the safety of various vaccineadministration techniques and the vaccine’s effects on broader demographics.

Background: The currently recommended pre-transfusion testing techniques for patients with autoantibodies are complex, time-consuming, and labor-intensive. Therefore, although the red blood cell (RBC) selection method using crossmatched RBC agglutination reaction grades (i.e., the “least incompatible” transfusion) is discouraged, many institutions still use it. We aimed to evaluate the effectiveness of this method combined with Rh subgroup phenotyping. Methods: We retrospectively investigated RBC transfusions from January 2019 to December 2021 in patients presenting as auto-control-positive via antibody identification (auto-control (+) group), where Rh subgroup phenotype-matched RBCs were selected based on the agglutination reaction grades of crossmatched units. For each study patient, an auto-control-negative patient was matched based on age, sex, department, and pre-transfusion Hb levels (auto-control (−) group). The mean Hb change per unit, transfusion-associated symptom/sign reports, and agglutination reaction grades upon crossmatching were analyzed. Results: In the auto-control (+) group, the Hb change per unit among different agglutination reaction grades of transfused RBCs and among different relative grades of transfused RBCs and crossmatching auto-controls was not significantly different (P=0.392 and P= 0.132, respectively). No significant difference was observed in Hb changes and transfusion-associated symptom/sign occurrence between the auto-control (+) and auto-control (−) groups (P=0.121 and P=0.822, respectively). In addition, no definite evidence of hemolysis in the auto-control (+) group was observed in the medical record review. Conclusions Together with Rh subgroup phenotyping, selecting the RBC unit with the lowest agglutination reaction grade upon crossmatching does not adversely affect transfusion efficiency.