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: Neutrophilic inflammation is a characteristic feature of idiopathic pulmonary fibrosis (IPF). S100 calcium-binding protein A9 (S100A9) is a neutrophil-derived protein involved in the development of neutrophil-related chronic inflammatory disorders. However, the role of S100A9 in IPF remains unclear. Methods: We used enzyme-linked immunosorbent assays to measure S100A9 levels in bronchoalveolar lavage fluid (BALF) and serum obtained from healthy controls (HCs) and patients with IPF, non-specific interstitial pneumonia, hypersensitivity pneumonitis, and sarcoidosis. Results: Compared with HCs, BALF S100A9 levels were significantly higher in IPF patients (P < 0.001), patients with hypersensitivity pneumonitis (P = 0.043), and patients with nonspecific interstitial pneumonia (P < 0.001). The S100A9 level in BALF of 0.093 ng/mL could distinguish IPF patients from HCs, with a specificity of 78.8% and a sensitivity of 81.6%. Similarly, the S100A9 level in BALF of 0.239 ng/mL had a specificity of 64.7% and a sensitivity of 66.7% for distinguishing IPF patients from patients with other interstitial lung diseases. Additionally, BALF S100A9 levels were significantly correlated with neutrophil counts (r = 0.356, P < 0.001) in BALF. IPF patients with S100A9 levels in BALF > 0.533 ng/ mL had lower survival rates, compared with patients who had levels ≤ 0.553 ng/mL (n = 49; hazard ratio [HR], 3.62; P = 0.021). Combination analysis revealed that IPF patients with S100A9 levels in BALF> 0.553 ng/mL or neutrophil percentages > 49.1% (n = 43) had significantly lower survival rates than patients with S100A9 levels in BALF ≤ 0.553 ng/mL and neutrophil percentages ≤ 49.1% (n = 41) (HR, 3.91; P = 0.014). Additionally, patients with serum S100A9 levels > 0.077 ng/mL (n = 29) had significantly lower survival rates than patients with levels ≤ 0.077 ng/mL (n = 53, HR, 2.52; P = 0.013). S100A9 was expressed on neutrophils and macrophages in BALF from IPF patients as well as α-smooth muscle actin positive cells in the lung tissues. Conclusion S100A9 is involved in the development and progression of IPF. Moreover, S100A9 levels in BALF and serum may be surrogate markers for IPF diagnosis and survival prediction, particularly when analyzed in combination with neutrophil percentages.

Purpose: Here we report a case of posterior chamber intraocular lens (IOL) dislocation into the subconjunctival space (pesudophacocele) following ocular trauma.Case summary: A 66-year-old male presented with ocular pain and decreased vision in the right eye following trauma with a metallic rod. The patient had a history of trabeculectomy, glaucoma drainage device implantation, transscleral cyclophotocoagulation, and cataract surgery for uveitic glaucoma and a cataract in the right eye. On examination, vision was hand movement, the intraocular pressure was 3 mmHg, and subconjunctival hemorrhage and hyphema were observed. After the resolution of hemorrhage, uveal tissue prolapse was seen nasally behind the corneal limbus and the IOL was found to be dislocated into the nasal subconjunctival space. There were no changes in the filtering bleb and tube compared to the pre-trauma status. The IOL was removed through a conjunctival incision because the patient refused any active treatment. Conclusions Pesudophacocele developed in a patient who had a history of glaucoma and cataract surgery in the injured eye. The IOL could not be assessed immediately after the trauma because of subconjunctival hemorrhage and hyphema. When the status of IOL is unclear or suspected to be dislocated after trauma, the possibility of pseudophacocele should be considered, in addition to the dislocation into the vitreous cavity.

Objective: Although fluid resuscitation is the cornerstone of treatment for sepsis, the role of body water status in sepsis is poorly understood. This study aimed to understand how body water and its distribution are modified in patients with sepsis and those with non-septic infection compared to healthy individuals. Methods: Two groups of adults presumed to have non-septic infection (n=87) and sepsis (n=54) were enrolled in this prospective study in a single emergency department, and they were compared to sex-, age-, and height-matched (1:3 ratio) healthy controls (n=11,190) from retrospective data in a health promotion center. Total body water (TBW), intracellular water (ICW), and extracellular water (ECW), determined using direct segmental multi-frequent bioelectrical impedance analysis (InBody S10) were expressed as indices for normalization by body weight (BW). The ratio of ECW to TBW (ECW/TBW) was evaluated to determine body water distribution. Results: TBW/BW, ICW/BW, and ECW/BW were significantly higher in the non-septic infection group than in the healthy group (P<0.001), but ECW/TBW was not significantly different (P=0.690). There were no differences in TBW/BW and ICW/BW between the sepsis and healthy groups (P=0.083 and P=0.963). However, ECW/BW and ECW/TBW were significantly higher in the sepsis group than in the healthy group (P<0.001). Conclusion Compared to the healthy group, the ratio of body water to BW was significantly increased in the non-septic infection group, while ECW/BW and ECW/TBW were significantly increased in the sepsis group. These indices could be utilized as diagnostic variables of body water deficit in septic patients.

Background/Aims: The clinical significance of partial virological response (PVR) in patients undergoing antiviral therapy is not well known. This study investigated whether PVR after 2 years of entecavir (ETV) therapy is associated with hepatocellular carcinoma (HCC) development in cirrhotic patients. Methods: A total of 472 naïve patients with hepatitis B virus (HBV)-associated cirrhosis who were treated with ETV for at least 2 years were retrospectively enrolled. Clinical characteristics, laboratory data, PVR, and noninvasive fibrosis markers (aspartate aminotransferase to platelet ratio and FIB-4 index) at 2 years after ETV commencement were analyzed for HCC risk. Results: After excluding those who developed HCC within 2 years of ETV therapy, 359 patients (mean age, 51±10 years; male 64.3%) were examined. During a median follow-up of 82 months, 80 patients developed HCC. In the univariate analysis, older age (hazard ratio [HR], 1.056; p<0.001), PVR (HR, 2.536; p=0.002), higher aspartate aminotransferase (HR, 1.018; p=0.005), lower albumin level (HR, 0.463; p<0.001), lower platelet count (HR, 0.993; p=0.01), and higher FIB-4 index (HR, 1.141; p<0.001) at 2 years after ETV commencement were risk factors for HCC. In the multivariate analysis, older age (HR, 1.046; 95% confidence interval [CI], 1.022 to 1.072; p<0.001), PVR (HR, 2.358; 95% CI, 1.310 to 4.245; p=0.004), and higher FIB-4 index (HR, 1.103; 95% CI, 1.035 to 1.177; p=0.003) were independent risk factors. Conclusions PVR and higher FIB-4 index after 2 years of ETV therapy were independent risk factors for HCC. Therefore, efforts to accomplish a complete virological response and reduce the FIB-4 index should be made.

Background: Ear-loop-type Korean Filter 94 masks (KF94 masks, equivalent to the N95 and FFP2) are broadly used in health care settings in Korea for the coronavirus disease 2019 pandemic. Methods: A prospective randomized open-label study was designed to identify differences in the fitting performance between mask wearing methods in three different types of KF94 mask with ear loops between January to March 2021. General-fitting involved wearing an earloop-type KF94 mask, and tight-fitting involved wearing a mask aided by a clip connecting the ear loops. Each of the 30 participants wore three types of masks according to a randomly assigned order in both methods and performed a total of six quantitative fit tests (QNFTs) according to the occupational safety and health administration protocol. Results: All fit factors (FFs) measured by the QNFT were significantly higher for tight-fitting method with the clip in all KF94 masks (P < 0.001). However, the total FFs were very low, with a median (interquartile range) of 6 (3–23) and 29 (9–116) for general-fitting and tight-fitting, respectively. When wearing tightly, the horizontal 3-fold type mask with adjustable ear-loop length had the highest FF, with a median of 125, and the QNFT pass rate (FF ≥ 100) increased significantly from 4 (13%) to 18 (60%). Conclusion Even with sufficient filter efficiency, ear-loop-type-KF94 masks do not provide adequate protection. However, in relatively low-risk environments, wearing a face-seal adjustable KF94 mask and tight wearing with a clip can improve respiratory protection for healthcare workers.

Background/Aims: Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a major regulator of Wnt signaling, which is involved in fibroblast dysfunction. Because its role has not been evaluated in idiopathic pulmonary fibrosis (IPF), we examined the clinical implications of ROR2 expression. Methods: ROR2 mRNA expression was measured using reverse transcription polymerase chain reaction in lung tissue-derived fibroblasts from IPF patients (n = 14) and from controls (n = 10). ROR2 protein was measured using enzyme-linked immunosorbent assay in primary fibroblasts from IPF patients (n = 14) and controls (n = 10), and in bronchoalveolar lavage (BAL) fluids obtained from normal controls (NC; n = 30). IPF patients (n = 84), and other patients with interstitial lung diseases, including nonspecific interstitial pneumonia (NSIP; n = 10), hypersensitivity pneumonitis (HP; n = 10), and sarcoidosis (n = 10). Results: ROR2 mRNA and protein levels were significantly higher in IPF fibroblasts than in controls (p = 0.003, p = 0.0017, respectively). ROR2 protein levels in BAL fluids from patients with IPF were significantly higher than in those from NC (p < 0.001), and from patients with NSIP (p = 0.006), HP (p = 0.004), or sarcoidosis (p = 0.004). Receiver operating characteristic curves showed a clear difference between IPF and NC in ROR2 protein level (area under the curve, 0.890; confidence interval, 0.829 to 0.950; p < 0.001). ROR2 protein levels were significantly higher in GAP stage III than in GAP stages I and II (p = 0.016). Conclusions ROR2 may be related to the development of IPF, and its protein level may be a useful and severity-dependent candidate marker for IPF.

Background/Aims: The clinical significance of partial virological response (PVR) in patients undergoing antiviral therapy is not well known. This study investigated whether PVR after 2 years of entecavir (ETV) therapy is associated with hepatocellular carcinoma (HCC) development in cirrhotic patients. Methods: A total of 472 naïve patients with hepatitis B virus (HBV)-associated cirrhosis who were treated with ETV for at least 2 years were retrospectively enrolled. Clinical characteristics, laboratory data, PVR, and noninvasive fibrosis markers (aspartate aminotransferase to platelet ratio and FIB-4 index) at 2 years after ETV commencement were analyzed for HCC risk. Results: After excluding those who developed HCC within 2 years of ETV therapy, 359 patients (mean age, 51±10 years; male 64.3%) were examined. During a median follow-up of 82 months, 80 patients developed HCC. In the univariate analysis, older age (hazard ratio [HR], 1.056; p<0.001), PVR (HR, 2.536; p=0.002), higher aspartate aminotransferase (HR, 1.018; p=0.005), lower albumin level (HR, 0.463; p<0.001), lower platelet count (HR, 0.993; p=0.01), and higher FIB-4 index (HR, 1.141; p<0.001) at 2 years after ETV commencement were risk factors for HCC. In the multivariate analysis, older age (HR, 1.046; 95% confidence interval [CI], 1.022 to 1.072; p<0.001), PVR (HR, 2.358; 95% CI, 1.310 to 4.245; p=0.004), and higher FIB-4 index (HR, 1.103; 95% CI, 1.035 to 1.177; p=0.003) were independent risk factors. Conclusions PVR and higher FIB-4 index after 2 years of ETV therapy were independent risk factors for HCC. Therefore, efforts to accomplish a complete virological response and reduce the FIB-4 index should be made.

Background: Ear-loop-type Korean Filter 94 masks (KF94 masks, equivalent to the N95 and FFP2) are broadly used in health care settings in Korea for the coronavirus disease 2019 pandemic. Methods: A prospective randomized open-label study was designed to identify differences in the fitting performance between mask wearing methods in three different types of KF94 mask with ear loops between January to March 2021. General-fitting involved wearing an earloop-type KF94 mask, and tight-fitting involved wearing a mask aided by a clip connecting the ear loops. Each of the 30 participants wore three types of masks according to a randomly assigned order in both methods and performed a total of six quantitative fit tests (QNFTs) according to the occupational safety and health administration protocol. Results: All fit factors (FFs) measured by the QNFT were significantly higher for tight-fitting method with the clip in all KF94 masks (P < 0.001). However, the total FFs were very low, with a median (interquartile range) of 6 (3–23) and 29 (9–116) for general-fitting and tight-fitting, respectively. When wearing tightly, the horizontal 3-fold type mask with adjustable ear-loop length had the highest FF, with a median of 125, and the QNFT pass rate (FF ≥ 100) increased significantly from 4 (13%) to 18 (60%). Conclusion Even with sufficient filter efficiency, ear-loop-type-KF94 masks do not provide adequate protection. However, in relatively low-risk environments, wearing a face-seal adjustable KF94 mask and tight wearing with a clip can improve respiratory protection for healthcare workers.

Background/Aims: Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a major regulator of Wnt signaling, which is involved in fibroblast dysfunction. Because its role has not been evaluated in idiopathic pulmonary fibrosis (IPF), we examined the clinical implications of ROR2 expression. Methods: ROR2 mRNA expression was measured using reverse transcription polymerase chain reaction in lung tissue-derived fibroblasts from IPF patients (n = 14) and from controls (n = 10). ROR2 protein was measured using enzyme-linked immunosorbent assay in primary fibroblasts from IPF patients (n = 14) and controls (n = 10), and in bronchoalveolar lavage (BAL) fluids obtained from normal controls (NC; n = 30). IPF patients (n = 84), and other patients with interstitial lung diseases, including nonspecific interstitial pneumonia (NSIP; n = 10), hypersensitivity pneumonitis (HP; n = 10), and sarcoidosis (n = 10). Results: ROR2 mRNA and protein levels were significantly higher in IPF fibroblasts than in controls (p = 0.003, p = 0.0017, respectively). ROR2 protein levels in BAL fluids from patients with IPF were significantly higher than in those from NC (p < 0.001), and from patients with NSIP (p = 0.006), HP (p = 0.004), or sarcoidosis (p = 0.004). Receiver operating characteristic curves showed a clear difference between IPF and NC in ROR2 protein level (area under the curve, 0.890; confidence interval, 0.829 to 0.950; p < 0.001). ROR2 protein levels were significantly higher in GAP stage III than in GAP stages I and II (p = 0.016). Conclusions ROR2 may be related to the development of IPF, and its protein level may be a useful and severity-dependent candidate marker for IPF.