Purpose: This study aimed to report the final analysis of time-on-treatment (TOT) and overall survival (OS) in patients with advanced-stage epidermal growth factor receptor (EGFR)+ non–small cell lung cancer (NSCLC) who received sequential afatinib and osimertinib and to compare the outcomes with other second-line regimens (comparator group). Materials and Methods: In this updated report, the existing medical records were reviewed and rechecked. TOT and OS were updated and analyzed according to clinical features using the Kaplan-Meier method and log-rank test. TOT and OS were compared with those of the comparator group, in which most patients received pemetrexed-based treatments. A multivariable Cox proportional hazard model was used to evaluate features that could affect survival outcomes. Results: The median observation time was 31.0 months. The follow-up period was extended to 20 months. A total of 401 patients who received first-line afatinib were analyzed (166 with T790M+ and second-line osimertinib, and 235 with unproven T790M and other second-line agents). Median TOTs on afatinib and osimertinib were 15.0 months (95% confidence interval [CI], 14.0 to 16.1) and 11.9 months (95% CI, 8.9 to 14.6), respectively. The median OS in the osimertinib group was 54.3 months (95% CI, 46.7 to 61.9), much longer than that in the comparator group. In patients who received osimertinib, the OS was longest with Del19+ (median, 59.1; 95% CI, 48.7 to 69.5). Conclusion This is one of the largest real-world studies reporting the encouraging activity of sequential afatinib and osimertinib in Asian patients with EGFR+ NSCLC who acquired the T790M mutation, particularly Del19+.

Purpose: Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. Materials and Methods: Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. Results: A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. Conclusion Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.

Chronic constipation is one of the most common digestive diseases encountered in clinical practice. Constipation manifests as a variety of symptoms, such as infrequent bowel movements, hard stools, feeling of incomplete evacuation, straining at defecation, a sense of anorectal blockage during defecation, and use of digital maneuvers to assist defecation. During the diagnosis of chronic constipation, the Bristol Stool Form Scale, colonoscopy, and a digital rectal examination are useful for objective symptom evaluation and differential diagnosis of secondary constipation. Physiological tests for functional constipation have complementary roles and are recommended for patients who have failed to respond to treatment with available laxatives and those who are strongly suspected of having a defecatory disorder. As new evidence on the diagnosis and management of functional constipation emerged, the need to revise the previous guideline was suggested. Therefore, these evidence-based guidelines have proposed recommendations developed using a systematic review and meta-analysis of the treatment options available for functional constipation. The benefits and cautions of new pharmacological agents (such as lubiprostone and linaclotide) and conventional laxatives have been described through a meta-analysis. The guidelines consist of 34 recommendations, including 3 concerning the definition and epidemiology of functional constipation, 9 regarding diagnoses, and 22 regarding managements. Clinicians (including primary physicians, general health professionals, medical students, residents, and other healthcare professionals) and patients can refer to these guidelines to make informed decisions regarding the management of functional constipation.

OBJECTIVES: Studies evaluating weight changes during the coronavirus disease 2019 (COVID-19) pandemic have yielded inconsistent results, and most of those studies were based on self-reported anthropometric measures. We investigated changes in body mass index (BMI), professionally measured waist circumference (WC), and metabolic syndrome components from before to during the pandemic in a sample of the adult population in Korea. METHODS: This retrospective study included 1,118 male and female (age≥18 years) who underwent health checkups at a university medical center between January 1, 2016 and March 31, 2022. Changes in BMI, lifestyles, and metabolic syndrome components during the pandemic were analyzed using the paired t-test, McNemar test, generalized estimating equations, and repeated-measures analysis of variance. RESULTS: Changes in body weight, BMI, and body fat percentage during the pandemic were not clinically significant. However, statistically significant results were found for decreased physical activity (p<0.001) and WC (p<0.001), and exacerbation of all metabolic syndrome components (except serum triglyceride levels). Moreover, the metabolic syndrome prevalence increased significantly from 20.2% to 31.2% during the pandemic (p<0.001). The prevalence of abdominal obesity and high fasting blood glucose levels also significantly increased from 2019 to 2021. CONCLUSIONS Metabolic syndrome, its components, and fat distribution worsened significantly after the implementation of social distancing and lockdowns, despite no clinically significant changes in body weight and BMI. Further studies on the post- pandemic period should investigate the long-term impact of social lockdowns on BMI and the prevalence of metabolic syndrome.

BACKGROUND AND OBJECTIVES: Although complete revascularization is known superior to incomplete revascularization in ST elevation myocardial infarction (STEMI) patients with multi-vessel coronary artery disease (MVCD), there are no definite instructions on the optimal timing of non-culprit lesions percutaneous coronary intervention (PCI). We compared 1-year clinical outcomes between 2 different complete multi-vessel revascularization strategies.METHODS: From the Korea Acute Myocardial Infarction Registry-National Institute of Health, 606 patients with STEMI and MVCD who underwent complete revascularization were enrolled from November 2011 to December 2015. The patients were assigned to multi-vessel single-staged PCI (SS PCI) group (n=254) or multi-vessel multi-staged PCI (MS PCI) group (n=352). Propensity score matched 1-year clinical outcomes were compared between the groups.RESULTS: At one year, MS PCI showed a significantly lower rate of all-cause mortality (hazard ratio [HR], 0.42; 95% confidential interval [CI], 0.19–0.92; p=0.030) compared with SS PCI. In subgroup analysis, all-cause mortality increased in SS PCI with cardiogenic shock (HR, 4.60; 95% CI, 1.54–13.77; p=0.006), age ≥65 years (HR, 4.00; 95% CI, 1.67–9.58, p=0.002), Killip class III/IV (HR, 7.32; 95% CI, 1.68–31.87; p=0.008), and creatinine clearance ≤60 mL/min (HR, 2.81; 95% CI, 1.10–7.18; p=0.031). After propensity score-matching, MS PCI showed a significantly lower risk of major adverse cardiovascular event than SS PCI.CONCLUSIONS: SS PCI was associated with worse clinical outcomes compared with MS PCI. MS PCI for non-infarct-related artery could be a better option for patients with STEMI and MVCD, especially high-risk patients.
Arteries ; Coronary Artery Disease ; Coronary Vessels ; Creatinine ; Humans ; Korea ; Mortality ; Myocardial Infarction ; Myocardial Revascularization ; Percutaneous Coronary Intervention ; Propensity Score ; Shock, Cardiogenic

BACKGROUND AND OBJECTIVES: Although complete revascularization is known superior to incomplete revascularization in ST elevation myocardial infarction (STEMI) patients with multi-vessel coronary artery disease (MVCD), there are no definite instructions on the optimal timing of non-culprit lesions percutaneous coronary intervention (PCI). We compared 1-year clinical outcomes between 2 different complete multi-vessel revascularization strategies. METHODS: From the Korea Acute Myocardial Infarction Registry-National Institute of Health, 606 patients with STEMI and MVCD who underwent complete revascularization were enrolled from November 2011 to December 2015. The patients were assigned to multi-vessel single-staged PCI (SS PCI) group (n=254) or multi-vessel multi-staged PCI (MS PCI) group (n=352). Propensity score matched 1-year clinical outcomes were compared between the groups. RESULTS: At one year, MS PCI showed a significantly lower rate of all-cause mortality (hazard ratio [HR], 0.42; 95% confidential interval [CI], 0.19–0.92; p=0.030) compared with SS PCI. In subgroup analysis, all-cause mortality increased in SS PCI with cardiogenic shock (HR, 4.60; 95% CI, 1.54–13.77; p=0.006), age ≥65 years (HR, 4.00; 95% CI, 1.67–9.58, p=0.002), Killip class III/IV (HR, 7.32; 95% CI, 1.68–31.87; p=0.008), and creatinine clearance ≤60 mL/min (HR, 2.81; 95% CI, 1.10–7.18; p=0.031). After propensity score-matching, MS PCI showed a significantly lower risk of major adverse cardiovascular event than SS PCI. CONCLUSIONS SS PCI was associated with worse clinical outcomes compared with MS PCI. MS PCI for non-infarct-related artery could be a better option for patients with STEMI and MVCD, especially high-risk patients.

We evaluated whether thrombus aspiration (TA) during primary percutaneous coronary intervention (PCI) reduces adverse clinical outcomes within 30-days and 1-year periods. There is no well-designed, Korean data about the clinical impact of intracoronary TA during primary PCI in patients with ST-segment elevation myocardial infarction (STEMI). From the Korea Acute Myocardial Infarction Registry-National Institute of Health, 3749 patients with STEMI undergoing primary PCI within 12 hours (60.8±12.9 years, 18.7% women) with pre-procedural Thrombolysis in Myocardial Infarction (TIMI) flow 0, 1 in coronary angiography were enrolled between November 2011 and December 2015. The patients were divided into two groups: PCI with TA (n=1630) and PCI alone (n=2119). The primary end-point was major adverse cardiac event (MACE), defined as the composite of cardiovascular death (CVD), recurrent MI and stroke for 30-days and 1-year. TA did not diminish the risk of MACE, all-cause mortality and CVD in all patients during 30-days or 1-year. After performing the propensity score matching, TA also did not reduce the risk of MACE (Hazard ratio (HR) with 95% Confidence Interval (CI):1.187 [0.863-1.633], p value=0.291), all-cause mortality (HR with 95% CI: 1.130 [0.776-1.647], p value=0.523) and CVD (HR with 95% CI: 1.222 [0.778-1.920], p value=0.384) during the 1-year period. In subgroup analysis, there was no benefit of clinical outcomes favoring PCI with TA. In conclusion, primary PCI with TA did not reduce MACE, all-cause mortality or CVD among the Korean patients with STEMI and pre-procedural TIMI flow 0, 1 during the 30-day and 1-year follow ups.

Sequence type (ST) 33 of Shiga toxin-producing Escherichia coli (STEC) strain O91:H14 has been proposed as a potential domestic clone of STEC in Korea because of its high prevalence among human patients with mild diarrhea or asymptomatic carriers. Herein, the clonal diversity of 17 STEC O91:H14 isolates of ST33 during 2003 to 2014 was analyzed by pulsed-field gel electrophoresis, including 14 isolates from human patients and 3 from retail meats. Their virulence characteristics, acid resistance, and antimicrobial susceptibility were also determined. Our results showed that all isolates were clustered mainly into three different pulsotypes and were likely low pathogenic without antimicrobial resistance.
Clone Cells ; Diarrhea ; Electrophoresis, Gel, Pulsed-Field ; Escherichia coli ; Humans ; Korea ; Meat ; Molecular Epidemiology ; Prevalence ; Shiga Toxin ; Shiga-Toxigenic Escherichia coli ; Virulence

Obesity and metabolic syndrome is a worldwide pandemic and associated with high cardiovascular risk. Metabolic endotoxemia (ME) is thought to be an underlying molecular mechanism. It triggers toll-like receptor 4-mediated inflammatory adipokines and causes a chronic low grade inflammatory status, which results in cardiovascular risk increase. Exercise is the best nonpharmacological treatment to improve prognosis. In this study, we examined the circulating endotoxin level in Korean obese women and investigated effects of exercise on it. Women over body mass index (BMI) 25 kg/m2 participated in a resistance training exercise, Curves. At baseline and after 12 weeks exercise, tests including blood samples were taken. In Korean obese women, the fasting endotoxin was 1.45 ± 0.11 EU/mL. Ingestion of a high calorie meal led to a peak level after 2 hours (postprandial 2 hours [PP2]) and a significant rise over the 4 hours (postprandial 4 hours [PP4]) in it (1.78 ± 0.15 and 1.75 ± 0.14 EU/mL for PP2 and PP4, P < 0.05 vs. fasting). After exercise, BMI and hip circumference were reduced significantly. The total cholesterol (TC) at fasting, PP2 and PP4 were decreased significantly. All levels of circulating endotoxin at fasting, PP2 and PP4 showed reduction. But, the peak change was only significant (baseline vs. 12 weeks for PP2; 1.78 ± 0.15 vs. 1.48 ± 0.06 EU/mL, P < 0.05). We report the circulating endotoxin level in Korean obese women for the first time. Also, we establish that energy intake leads to endotoxemia and exercise suppresses the peak endotoxemia after meal. It suggests an impact for a better prognosis in obese women who follow regular exercise.
Adipokines ; Body Mass Index ; Cholesterol ; Eating ; Endotoxemia* ; Endotoxins ; Energy Intake ; Fasting ; Female ; Gastrointestinal Microbiome ; Hip ; Humans ; Lipopolysaccharides ; Meals ; Obesity* ; Pandemics ; Prognosis ; Resistance Training ; Toll-Like Receptors

BACKGROUND: The relationship between serum homocysteine levels and non-alcoholic fatty liver disease is poorly understood. This study aims to investigate the sex-specific relationship between serum homocysteine level and non-alcoholic fatty liver disease in the Korean population. METHODS: This cross-sectional study included 150 men and 132 women who participated in medical examination programs in Korea from January 2014 to December 2014. Patients were screened for fatty liver by abdominal ultrasound and patient blood samples were collected to measure homocysteine levels. Patients that consumed more than 20 grams of alcohol per day were excluded from this study. RESULTS: The homocysteine level (11.56 vs. 8.05 nmol/L) and the proportion of non-alcoholic fatty liver disease (60.7% vs. 19.7%) were significantly higher in men than in women. In men, elevated serum homocysteine levels were associated with a greater prevalence of non-alcoholic fatty liver disease (quartile 1, 43.6%; quartile 4, 80.6%; P=0.01); however, in females, there was no significant association between serum homocysteine levels and the prevalence of non-alcoholic fatty liver disease. In the logistic regression model adjusted for age and potential confounding parameters, the odds ratio for men was significantly higher in the uppermost quartile (model 3, quartile 4: odds ratio, 6.78; 95% confidential interval, 1.67 to 27.56); however, serum homocysteine levels in women were not associated with non-alcoholic fatty liver disease in the crude model or in models adjusted for confounders. CONCLUSION: Serum homocysteine levels were associated with the prevalence of non-alcoholic fatty liver disease in men.
Cross-Sectional Studies ; Fatty Liver ; Female ; Homocysteine* ; Humans ; Korea ; Logistic Models ; Male ; Non-alcoholic Fatty Liver Disease* ; Odds Ratio ; Prevalence ; Sex Characteristics* ; Ultrasonography