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: Since the emergence of hypervirulent strains of Clostridioides difficile, the incidence of C. difficile infections (CDI) has increased significantly. Methods: To assess the incidence of CDI in Korea, we conducted a prospective multicentre observational study from October 2020 to October 2021. Additionally, we calculated the incidence of CDI from mass data obtained from the Health Insurance Review and Assessment Service (HIRA) from 2008 to 2020. Results: In the prospective study with active surveillance, 30,212 patients had diarrhoea and 907 patients were diagnosed with CDI over 1,288,571 patient-days and 193,264 admissions in 18 participating hospitals during 3 months of study period; the CDI per 10,000 patientdays was 7.04 and the CDI per 1,000 admission was 4.69. The incidence of CDI was higher in general hospitals than in tertiary hospitals: 6.38 per 10,000 patient-days (range: 3.25–12.05) and 4.18 per 1,000 admissions (range: 1.92–8.59) in 11 tertiary hospitals, vs. 9.45 per 10,000 patient-days (range: 5.68–13.90) and 6.73 per 1,000 admissions (range: 3.18–15.85) in seven general hospitals. With regard to HIRA data, the incidence of CDI in all hospitals has been increasing over the 13-year-period: from 0.3 to 1.8 per 10,000 patient-days, 0.3 to 1.6 per 1,000 admissions, and 6.9 to 56.9 per 100,000 population, respectively. Conclusion The incidence of CDI in Korea has been gradually increasing, and its recent value is as high as that in the United State and Europe. CDI is underestimated, particularly in general hospitals in Korea.

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.

This study aimed to evaluate the differences in the baseline characteristics and patterns of antibiotic usage among hospitals based on their participation in the Korea National Antimicrobial Use Analysis System (KONAS). We obtained claims data from the National Health Insurance for inpatients admitted to all secondary- and tertiary-care hospitals between January 2020 and December 2021 in Korea. 15.9% (58/395) of hospitals were KONAS participants, among which the proportion of hospitals with > 900 beds (31.0% vs.2.6%, P < 0.001) and tertiary care (50.0% vs. 5.2%, P < 0.001) was higher than that among non-participants. The consumption of antibiotics targeting antimicrobial-resistant gram positive bacteria (33.7 vs. 27.1 days of therapy [DOT]/1,000 patient-days, P = 0.019) and antibiotics predominantly used for resistant gram-negative bacteria (4.8 vs. 3.7 DOT/1,000 patient-days, P = 0.034) was higher in KONAS-participating versus -non-participating hospitals. The current KONAS data do not fully represent all secondary- and tertiary-care hospitals in Korea; thus, the KONAS results should be interpreted with caution.

Parkinson’s disease (PD) which has various pathological mechanisms, recently, it is attracting attention to the mechanism via microbiome-gut-brain axis. 6-Shogaol, a representative compound of ginger, have been known for improving PD phenotypes by reducing neuroinflammatory responses. In the present study, we investigated whether 6-shogaol and ginger attenuate degeneration induced by Proteus Mirabilis(P. mirabilis) on the intestine and brain, simultaneously. C57BL/6J mice received P. mirabilis for 5 days. Ginger (300 mg/kg) and 6-shogaol (10 mg/kg) were treated by gavage feeding for 22 days including the period of P. mirabilis treatment. Results showed that 6-shogaol and ginger improved motor dysfunction and dopaminergic neuronal death induced by P. mirabilis treatment. In addition, they suppressed P. mirabilis-induced intestinal barrier disruption, pro-inflammatory signals such as toll-like receptor and TNF-α, and intestinal α-synuclein aggregation. Moreover, ginger and 6-shogaol significantly inhibited neuroinflammation and α-synuclein in the brain. Taken together, 6-shogaol and ginger have the potential to ameliorate PD-like motor behavior and degeneration of dopaminergic neurons induced by P. mirabilis in mice. Here, these findings are meaningful in that they provide the first experimental evidence that 6-shogaol might attenuate PD via regulating gut-brain axis.

A reduced estimated glomerular filtration rate (eGFR) is a predictor for mortality in patients with acute myocardial infarction (AMI). This study aimed to compare mortality according to the GFR and eGFR calculation methods during long-term clinical follow-ups. Using the Korean Acute Myocardial Infarction Registry-National Institutes of Health Data, 13,021 patients with AMI were included in this study. Patients were divided into the surviving (n=11,503, 88.3%) and deceased (n=1,518, 11.7%) groups.Clinical characteristics, cardiovascular risk factors, and 3-year mortality-related factors were analyzed. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations. The surviving group was younger than the deceased group (62.6±12.4 vs. 73.6±10.5 years, p＜0.001), whereas the deceased group had higher hypertension and diabetes prevalences than the surviving group. A high Killip class was more frequently observed in the deceased group. eGFR was significantly lower in the deceased group (82.2±24.1 vs. 55.2±28.6 ml/min/1.73 m 2 , p＜0.001). Multivariate analysis revealed that low eGFR was an independent risk factor for mortality during the 3-year follow-up. The CKD-EPI equation was more useful for predicting mortality than the MDRD equation (0.766; 95% confidence interval [CI], 0.753-0.779 vs. 0.738; 95% CI, 0.724-0.753; p=0.001). Decreased renal function was a significant predictor of mortality after 3 years in patients with AMI. The CKD-EPI equation was more useful for predicting mortality than the MDRD equation.

Background/Aims: We evaluated the role of next-generation sequencing (NGS)-based disease monitoring for elderly patients diagnosed with acute myeloid leukemia (AML) who received decitabine therapy. Methods: A total of 123 patients aged > 65 years with AML who received decitabine were eligible. We analyzed the dynamics of variant allele frequency (VAF) in 49 available follow-up samples after the fourth cycle of decitabine. The 58.6% VAF clearance (Δ, [VAF at diagnosis − VAF at follow-up] × 100 / VAF at diagnosis) was the optimal cut-off for predicting overall survival (OS). Results: The overall response rate was 34.1% (eight patients with complete remission [CR], six of CR with incomplete hematologic recovery, 22 with partial responses, and six with morphologic leukemia-free status). Responders (n = 42) had significantly better OS compared with non-responders (n = 42) (median, 15.3 months vs. 6.5 months; p < 0.001). Of the 49 patients available for follow-up targeted NGS analysis, 44 had trackable gene mutations. The median OS of patients with ΔVAF ≥ 58.6% (n=24) was significantly better than that of patients with ΔVAF < 58.6% (n = 19) (20.5 months vs. 9.8 months, p = 0.010). Moreover, responders with ΔVAF ≥ 58.6% (n = 20) had a significantly longer median OS compared with responders with VAF < 58.6% (n = 11) (22.5 months vs. 9.8 months, p = 0.004). Conclusions This study suggested that combining ΔVAF ≥ 58.6%, a molecular response, with morphologic and hematologic responses can more accurately predict OS in elderly AML patients after decitabine therapy.

Background: Non-palpable splenomegaly in patients with polycythemia vera (PV) has seldom been addressed. In this retrospective study, we evaluated non-palpable, volumetric splenomegaly defined based on age- and body surface area (BSA)–matched criteria in patients with PV diagnosed according to the 2016 World Health Organization diagnostic criteria. Methods: Patients with PV who underwent abdominal computed tomography (CT) and who had palpable splenomegaly at diagnosis from January 1991 to December 2020 at Chungnam National University Hospital were enrolled. The spleen volume of each patient was determined by volumetric analysis of abdominal CT and adjusted for the patient’s age and BSA. Then the degree of splenomegaly was classified as no splenomegaly, borderline volumetric splenomegaly, overt volumetric splenomegaly, or palpable splenomegaly. Results: Of the 87 PV patients enrolled, 15 (17.2%) had no splenomegaly, whereas 17 (19.5%), 45 (51.7%), and 10 (11.5%) had borderline volumetric, overt volumetric, and palpable splenomegaly, respectively. The degree of splenomegaly did not affect the cumulative incidence of thrombotic vascular events (10-year incidence: 7.7%, 0%, 22.3%, and 50.7%, respectively, P = 0.414). By contrast, splenomegaly tended to adversely affect myelofibrotic transformation (10-year cumulative incidence: 0%, 0%, 7.1%, and 30.3%, respectively, P = 0.062). Moreover, the cumulative incidence of myelofibrotic transformation was significantly higher in patients with overt volumetric or palpable splenomegaly than those with no or borderline volumetric splenomegaly (10-year incidence: 0% vs. 10.3%, respectively; 15-year incidence: 0% vs. 26.3%, respectively, P = 0.020). Overall survival (OS) differed among patients with different degrees of splenomegaly (15-year OS: 100%, 78.6%, 71.7%, and 51.9%, respectively, P = 0.021). Conclusion The degree of splenomegaly, including volumetric splenomegaly, based on ageand BSA-matched reference spleen volumes at diagnosis reflects disease progression in PV patients. Therefore, volumetric splenomegaly should be evaluated at the time of diagnosis and taken into consideration when predicting the prognosis of patients with PV.