PURPOSE: We investigated the effect of the protease inhibitor, aprotinin, on mean arterial pressure (MAP), hematocrit (Hct), blood loss, and survival rate in rats with experimental splenic injury. METHODS: We created an experimental splenic injury model in anesthetized rats by cutting the splenic parenchyma into three fragments. We analyzed the effect of aprotinin on three different treatment groups. The aprotinin treatment group received a single dose of 30,000 U/kg of aprotinin in 10 ml/kg normal saline, the tranexamic acid group was treated with a single dose of 100 mg/kg of tranexamic acid in 10ml/kg normal saline, and the saline control group was treated with only 10 ml/kg normal saline. In addition, a sham-operated group (laparotomy without splenectomy) was treated with 10 ml/kg normal saline. RESULTS: MAP was higher in the sham-operated group and the aprotinin group than in the other groups. There were no significant differences for hematocrit except that the saline group exhibited a lower level than the other groups at the six-hour time point. The amount of intraperitoneal blood loss in the sham-operated and aprotinin groups due to splenic injury was significantly lower than in the tranexamic acid and saline groups. The survival rate in the aprotinin group was similar to the tranexamic acid group, but, the survival rate of the aprotinin-treated group was statistically higher than that of the saline control group. CONCLUSION: Hemodynamic changes resulting from splenic injury can be diminished by aprotinin treatment. Aprotinin could be considered in preference to other drugs as a first line treatment in hemodynamically unstable splenic injury patients.
Animals ; Aprotinin* ; Arterial Pressure ; Hematocrit ; Hemodynamics ; Hemoperitoneum ; Hemorrhage* ; Humans ; Protease Inhibitors ; Rats* ; Splenic Rupture ; Survival Rate ; Tranexamic Acid

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.