Purpose: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). Materials and Methods: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). Results: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. Conclusion Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

Background: Sutureless valves are widely used in aortic valve replacement surgery, with Perceval valves and Intuity valves being particularly prominent. However, concerns have been raised about postoperative thrombocytopenia with Perceval valves (Corcym, UK). We conducted a comparative analysis with the Intuity valve (Edwards Lifesciences, USA), and assessed how thrombocytopenia affected patient and transfusion outcomes. Methods: Among 595 patients who underwent aortic valve replacement from June 2016 to March 2023, sutureless valves were used in 53 (Perceval: n=23; Intuity: n=30). Platelet counts were monitored during hospitalization and outpatient visits. Daily platelet count changes were compared between groups, and the results from patients who underwent procedures using Carpentier Edwards Perimount Magna valves were used as a reference group. Results: Compared to the Intuity group, the Perceval group showed a significantly higher amount of platelet transfusion (5.48±1.64 packs vs. 0.60±0.44 packs, p=0.008). During the postoperative period, severe thrombocytopenia (<50,000/μL) was significantly more prevalent in the Perceval group (56.5%, n=13) than in the Intuity group (6.7%, n=2). After initial postoperative depletion, daily platelet counts increased, with significant differences observed in the extent of improvement between the Perceval and Intuity groups (p<0.001).However, there was no significant difference in early mortality or the incidence of neurological complications between the 2 groups. Conclusion The severity of postoperative thrombocytopenia differed significantly between the Perceval and Intuity valves. The Perceval group showed a significantly higher prevalence of severe thrombocytopenia and higher platelet transfusion volumes. However, thrombocytopenia gradually recovered during the postoperative period in both groups, and the early outcomes were similar in both groups.

Background: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. Methods: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. Results: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582). Conclusion In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

Scrub typhus develops after the individual is bitten by a trombiculid mite infected with Orientia tsutsugamushi. Since it has been reported that pneumonia is frequently observed in patients with scrub typhus, we investigated whether intranasal (i.n.) vaccination with the outer membrane protein of O. tsutsugamushi (OMPOT) would induce a protective immunity against O. tsutsugamushi infection. It was particular interest that when mice were infected with O. tsutsugamushi, the bacteria disseminated into the lungs, causing pneumonia. The i.n. vaccination with OMPOT induced IgG responses in serum and bronchoalveolar lavage (BAL) fluid. The anti-O. tsutsugamushi IgA Abs in BAL fluid after the vaccination showed a high correlation of the protection against O. tsutsugamushi. The vaccination induced strong Ag-specific Th1 and Th17 responses in the both spleen and lungs. In conclusion, the current study demonstrated that i.n. vaccination with OMPOT elicited protective immunity against scrub typhus in mouse with O. tsutsugamushi infection causing subsequent pneumonia.

Purpose: The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program. Materials and Methods: Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected. Results: Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data. Conclusion This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

PURPOSE: This study aimed to identify time-dependent prognostic factors and demonstrate the time-dependent effects of important prognostic factors in patients with advanced gastric cancer (AGC). MATERIALS AND METHODS: We retrospectively evaluated 3,653 patients with AGC who underwent curative standard gastrectomy between 1991 and 2005 at the Korea Cancer Center Hospital. Multivariate survival analysis with Cox proportional hazards regression was used in the analysis. A non-proportionality test based on the Schoenfeld residuals (also known as partial residuals) was performed, and scaled Schoenfeld residuals were plotted over time for each covariate. RESULTS: The multivariate analysis revealed that sex, depth of invasion, metastatic lymph node (LN) ratio, tumor size, and chemotherapy were time-dependent covariates violating the proportional hazards assumption. The prognostic effects (i.e., log of hazard ratio [LHR]) of the time-dependent covariates changed over time during follow-up, and the effects generally diminished with low slope (e.g., depth of invasion and tumor size), with gentle slope (e.g., metastatic LN ratio), or with steep slope (e.g., chemotherapy). Meanwhile, the LHR functions of some covariates (e.g., sex) crossed the zero reference line from positive (i.e., bad prognosis) to negative (i.e., good prognosis). CONCLUSIONS: The time-dependent effects of the prognostic factors of AGC are clearly demonstrated in this study. We can suggest that time-dependent effects are not an uncommon phenomenon among prognostic factors of AGC.
Follow-Up Studies ; Gastrectomy ; Humans ; Korea ; Lymphatic Metastasis ; Lymph Nodes ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Stomach Neoplasms*

PURPOSE: Peritoneal lavage cytology is part of the routine staging workup for patients with advanced gastric cancer. However, no quality assurance study has been conducted to show variations or biases in peritoneal lavage cytology results. The aim of this study was to demonstrate a test execution variation in peritoneal lavage cytology between investigating surgeons. MATERIALS AND METHODS: A prospective cohort study was designed for determination of the positive rate of peritoneal lavage cytology using a liquid-based preparation method in patients with potentially curable advanced gastric cancer (cT2~4/N0~2/M0). One hundred thirty patients were enrolled and underwent laparotomy, peritoneal lavage cytology, and standard gastrectomy, which were performed by 3 investigating surgeons. Data were analyzed using the chi-square test and a logistic regression model. RESULTS: The overall positive peritoneal cytology rate was 10.0%. Subgroup positive rates were 5.3% in pT1 cancer, 2.0% in pT2/3 cancer, 11.1% in pT4a cancer, and 71.4% in pT4b cancer. In univariate analysis, positive peritoneal cytology showed significant correlation with pT stage, lymphatic invasion, vascular invasion, ascites, and the investigating surgeon. We found the positive rate to be 2.1% for surgeon A, 10.2% for surgeon B, and 20.6% for surgeon C (P=0.024). Multivariate analysis identified pT stage, ascites, and the investigating surgeon to be significant risk factors for positive peritoneal cytology. CONCLUSIONS: The peritoneal lavage cytology results were significantly affected by the investigating surgeon, providing strong evidence of test execution variation that could be related to poor diagnostic accuracy and stage migration in patients with advanced gastric cancer.
Ascites ; Bias (Epidemiology) ; Cohort Studies ; Gastrectomy ; Humans ; Laparotomy ; Logistic Models ; Methods ; Multivariate Analysis ; Peritoneal Lavage* ; Prospective Studies ; Risk Factors ; Stomach Neoplasms*

The structures of the intact synaptosomal plasma membrane vesicles (SPMVs) isolated from bovine cerebral cortexs, and the outer and the inner monolayer separately, were evaluated with 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1,3-di(1-pyrenyl)propane (Py-3-Py) as fluorescent reporters and trinitrophenyl groups as quenching agents. The methanol increased bulk rotational and lateral mobilities of SPMVs lipid bilayers. The methanol increased the rotational and lateral mobilities of the outer monolayers more than of the inner monolayers. n-(9-Anthroyloxy)stearic acid (n-AS) were used to evaluate the effect of the methanol on the rotational mobility at the 16, 12, 9, 6, and 2 position of aliphatic chains present in phospholipids of the SPMVs outer monolayers. The methanol decreased the anisotropy of the 16-(9-anthroyloxy)palmitic acid (16-AP), 12-(9-anthroyloxy)stearic acid (12-AS), 9-(9-anthroyloxy)stearic acid (9-AS), and 6-(9-anthroyloxy)stearic acid (6-AS) in the SPMVs outer monolayer but it increased the anisotropy of 2-(9-anthroyloxy)stearic acid (2-AS) in the monolayers. The magnitude of the increased rotational mobility by the methanol was in the order at the position of 16, 12, 9, and 6 of aliphatic chains in phospholipids of the outer monolayers. Furthermore, the methanol increased annular lipid fluidity and also caused membrane proteins to cluster. The important finding is that was far greater increase by methanol in annular lipid fluidity than increase in lateral and rotational mobilities by the methanol. Methanol alters the stereo or dynamics of the proteins in the lipid bilayers by combining with lipids, especially with the annular lipids. In conclusion, the present data suggest that methanol, in additions to its direct interaction with proteins, concurrently interacts with membrane lipids, fluidizing the membrane, and thus inducing conformational changes of proteins known to be intimately associated with membranes lipids.
Anisotropy ; Cell Membrane ; Cerebral Cortex ; Diphenylhexatriene ; Lipid Bilayers ; Membrane Lipids ; Membrane Proteins ; Membranes ; Methanol ; Neurons ; Palmitic Acids ; Phospholipids ; Proteins ; Stearic Acids

In order to screen microsatellites for conservation genetics studies of the species, a total of 23 microsatellite loci from Korean goral (Naemorhedus caudatus), including 15 previously developed loci and 8 new loci in this study, were tested. Eleven microsatellites were screened and subjected to cross-species amplification using a test panel of four Caprinae species, Japanese serows (Capricornis crispus), Chinese gorals (Naemorhedus goral), Northern chamois (Rupicapra rupicapra) and domestic goats (Capra hircus). In addition, all eleven microsatellites (SY3A, SY12A, SY12B, SY48, SY58, SY71, SY76, SY84, SY84B, SY112, and SY129) satisfied the criteria to be a core set of microsatellites. This core set of microsatellites and cross-species amplification of Korean goral microsatellites were found to be helpful for high-resolution studies for conservation and management of Korean goral and other endangered Caprinae species.
Animals ; Conservation of Natural Resources ; Genetic Variation ; Hybridization, Genetic/*genetics ; Microsatellite Repeats/*genetics ; Republic of Korea ; Ruminants/*genetics

We determined the genetic diversity and distance between Jeju and Thoroughbred horses by genotyping for 20 microsatellite loci consisting of (TG)n repetitive sequence. The expected heterozygosity ranged from 0.1 to 0.789 in the Jeju horses and from 0.505 to 0.824 in the Thoroughbred horses. Polymorphic information content (PIC) values ranged from 0.09 to 0.709 in the Jeju horses and 0.365 to 0.730 in Thoroughbred horses. There were no significant differences in heterozygosity and PIC values between Jeju and Thoroughbred horsesHowever, LEX035 was estimated relatively high heterozygosity (0.789) and PIC value 0.709) in Jeju horses and LEX050 was respectively 0.824, and 0.730 in the Thoroughbred horses. We may conclude that the genetic differentiation was low between Jeju and Thoroughbred horses. LEX 050, LEX055, LEX059 and LEX 063 could be used as geneticmarkers for differentiating Jeju from Thoroughbred horses.
DNA ; Genetic Markers ; Genetic Variation ; Horses ; Korea ; Microsatellite Repeats ; Polymorphism, Genetic ; Repetitive Sequences, Nucleic Acid