Background/Aims: Standard triple therapy (STT; proton pump inhibitor [PPI]+clarithromycin+amoxicillin) used for Helicobacter pylori (H. pylori) eradication has shown low treatment success rates in recent years, which is most likely attributable to increased clarithromycin resistance. In this study, we compared treatment success rates of tailored therapy (TT) using real-time polymerase chain reaction (RT-PCR) and empirical STT. Methods: This retrospective study included 650 patients with H. pylori infection, who visited Eunpyeong St. Mary’s Hospital in Korea; 343 patients received TT based on RT-PCR assays, and 307 patients received STT. Eradication success was defined as a negative 13C-urea breath test result 4~8 weeks after treatment completion. Patients who failed first-line therapy and those with clarithromycin resistance received bismuth-containing quadruple therapy (BQT; PPI+bismuth+metronidazole+tetracycline). Results: Intention-to-treat analysis showed that H. pylori eradication rates were higher in patients who received RT-PCR–based TT than in those who were treated using empirical STT (80.5% [190/236] vs. 70.4% [216/307], P=0.069). Per-protocol (PP) analysis showed similar results (84.4% [190/225] vs. 74.7% [216/289], P=0.007). PP analysis showed that 7-day TT treatment was associated with a higher eradication rate than that observed with 10- to 14-day STT (85.2% [178/209] vs. 73.8% [59/80], P=0.029). The clarithromycin resistance rate was 27.9% (87/312). The eradication success rate was 89.2% (74/83) in patients with clarithromycin resistance, who received BQT as first-line therapy. Conclusions The treatment success rate was higher in patients who received 7-day RT-PCR–based TT than in those who were administered 10- to 14-day empirical treatment.

Background and Objectives: Pulmonary arterial hypertension (PAH) is a rare but fatal disease. Recent advances in PAH-specific drugs have improved its outcomes, although the healthcare burden of novel therapeutics may lead to a discrepancy in outcomes between developing and developed countries. We analyzed how the epidemiology and clinical features of PAH has changed through the rapidly advancing healthcare infrastructure in South Korea. Methods: PAH was defined according to a newly devised 3-component algorithm. Using a nationwide health insurance claims database, we delineated annual trends in the prevalence, incidence, medication prescription pattern, and 5-year survival of PAH in Korea. Cumulative survival and potential predictors of mortality were also assessed among 2,151 incident PAH cases. Results: Between 2002 or 2004 and 2018, the prevalence and incidence of PAH increased 75-fold (0.4 to 29.9 per million people) and 12-fold (0.5 to 6.3 per million person-years), respectively. The proportion of patients on combination PAH-specific drug therapy has also steadily increased up to 29.0% in 2018. Among 2,151 incident PAH cases (median [interquartile range] age, 50 [37–62] years; 67.2% female), the 5-year survival rate and median survival duration were 71.8% and 13.1 years, respectively. Independent predictors of mortality were age, sex, etiology of PAH, diabetes, dyslipidemia, and chronic kidney disease. Conclusions This nationwide study delineated that the prevalence and incidence of PAH have grown rapidly in Korea since the early 2000s. The use of combination therapy has also increased, and the 5-year survival rate of PAH in Korea was similar to those in western countries.

Purpose: K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods. Materials and Methods: Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers). Results: In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively. Conclusion The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

Purpose: We investigated the effects of cold water immersion (CWI) treatment during half-time break on performance related physiological indices during second half soccer match. Methods: Twenty-two collegiate soccer players participated in the study. Subjects undertook 3 minutes head out seated with whole body immersion at 19 o C to 21 o C. Total four venous blood samples were collected and analyzed for markers of ionic regulations and inflammatory (interleukin [IL]-1b, IL-6, IL-8, IL-10, tumor necrosis factor-α , and vascular endothelial growth factor) and immune functions (immunoglobulin [Ig] G, IgG2, IgG2, IgG3, IgG4, IgA, and IgM). Results: Partial oxygen concentration and %SO 2 level was lowered in CWI. Hemoglobin and hematocrit values were not significantly different between experimental groups. While there was no notable effect was shown in Na ＋ and Ca 2＋ , K ＋ concentration was higher in CWI during second half match. There were no effects in any of inflammatory and/or anti-inflammatory cytokines and Ig. Conclusion These results suggest that CWI during half time break exert positively affects in buffering capacity and promote oxygen delivery to the actively recruited skeletal muscle, possibly results in improve soccer performance during second half match.

Purpose: Next-generation sequencing (NGS) can facilitate precision medicine approaches in metastatic colorectal cancer (mCRC) patients. We investigated the molecular profiling of Korean mCRC patients under the K-MASTER project which was initiated in June 2017 as a nationwide precision medicine oncology clinical trial platform which used NGS assay to screen actionable mutations. Materials and Methods: As of 22 January 2020, total of 994 mCRC patients were registered in K-MASTER project. Targeted sequencing was performed using three platforms which were composed of the K-MASTER cancer panel v1.1 and the SNUH FIRST Cancer Panel v3.01. If tumor tissue was not available, cell-free DNA was extracted and the targeted sequencing was performed by Axen Cancer Panel as a liquid biopsy. Results: In 994 mCRC patients, we found 1,564 clinically meaningful pathogenic variants which mutated in 71 genes. Anti-EGFR therapy candidates were 467 patients (47.0%) and BRAF V600E mutation (n=47, 4.7%), deficient mismatch repair/microsatellite instability–high (n=15, 1.5%), HER2 amplifications (n=10, 1.0%) could be incorporated with recently approved drugs. The patients with high tumor mutation burden (n=101, 12.7%) and DNA damaging response and repair defect pathway alteration (n=42, 4.2%) could be enrolled clinical trials with immune checkpoint inhibitors. There were more colorectal cancer molecular alterations such as PIK3CA, KRAS G12C, atypical BRAF, and HER2 mutations and even rarer but actionable genes that approved or ongoing clinical trials in other solid tumors. Conclusion K-MASTER project provides an intriguing background to investigate new clinical trials with biomarkers and give therapeutic opportunity for mCRC patients.

We aim to investigate the effect of fronto-temporal transcranial direct current stimulation (tDCS) on the interactions among functional networks and its association with psychotic symptoms. In this pilot study, we will determine possible candidate functional networks and an adequate sample size for future research. Seven schizophrenia patients with treatment-refractory auditory hallucinations underwent tDCS twice daily for 5 days. Resting-state fMRI data and measures of the severity of psychotic symptoms were acquired at baseline and after completion of the tDCS sessions. At baseline, decreased functional network interaction was negatively correlated with increased hallucinatory behavior. After tDCS, the previously reduced functional network connectivity significantly increased. Our results showed that fronto-temporal tDCS could possibly remediate aberrant hallucination-related functional network interactions in patients with schizophrenia.
Hallucinations ; Humans ; Magnetic Resonance Imaging ; Neuroimaging ; Pilot Projects ; Sample Size ; Schizophrenia ; Transcranial Direct Current Stimulation

PURPOSE: Eosinophilic inflammation is a key component of severe asthma (SA). However, there has been no reliable serum biomarker for the eosinophilic inflammation of SA. We hypothesized that serum eosinophil-derived neurotoxin (EDN) could predict the eosinophilic inflammation of SA in adult asthmatics. METHODS: Severe asthmatics (n = 235), nonsevere asthmatics (n = 898), and healthy controls (n = 125) were enrolled from Ajou University Hospital, South Korea. The serum levels of EDN and periostin were measured by enzyme-linked immunosorbent assay and compared between severe and nonsevere asthmatics. Their associations with total eosinophil count (TEC) and clinical parameters were evaluated; clinical validation of the K-EDN kit for the measurement of serum EDN was evaluated. RESULTS: Severe asthmatics were older and had longer disease duration with significantly lower levels of forced expiratory volume in 1 second and methacholine PC20 than nonsevere asthmatics. Significant differences were found in TEC or sputum eosinophil count (%) between the groups. The serum levels of EDN and periostin were significantly higher in severe asthmatics than in nonsevere asthmatics and in healthy controls (all P < 0.05). Although significant correlations were found between serum EDN levels measured by the 2 kits (ρ = 0.545, P < 0.0001), higher correlation coefficients between serum EDN levels measured by the K-EDN kit and TEC were higher (ρ = 0.358, P < 0.0001) than those between serum EDN levels measured by the MBL kit and TEC (ρ = 0.319, P < 0.0001) or serum periostin level (ρ = 0.222, P < 0.0001). Multivariate regression analysis demonstrated that serum EDN levels measured by the K-EDN kit predicted the phenotype of SA (P = 0.003), while 2 other biomarkers did not. CONCLUSIONS: The serum EDN level may be a useful biomarker for assessing asthma severity in adult asthmatics.
Adult ; Asthma ; Biomarkers ; Enzyme-Linked Immunosorbent Assay ; Eosinophil-Derived Neurotoxin ; Eosinophils ; Forced Expiratory Volume ; Humans ; Inflammation ; Korea ; Methacholine Chloride ; Phenotype ; Sputum

OBJECTIVES: The purpose of this study was to compare aripiprazole versus bupropion augmentation therapy in older adult patients with major depressive disorder unresponsive to selective serotonin reuptake inhibitors(SSRIs).METHODS: This is a post-hoc analysis of a 6-week, randomized prospective open-label multi-center study in thirty older adult patients with major depressive disorder. Participants were randomized to receive aripiprazole(N=16, 2.5–10mg/day) or bupropion(N=14, 150–300mg/day) for 6 weeks. Montgomery Asberg Depression Rating Scale (MADRS), 17-item Hamilton Depression Rating scale(HAM-D17), Iowa Fatigue Scale, Drug-Induced Extrapyramidal Symptoms Scale, Psychotropic-Related Sexual Dysfunction Questionnaire scores, and Clinical Global Impression-Severity (CGI-S) were obtained at baseline and after one, two, four, and six weeks. Changes on individual items of HAM-D17 were assessed as well as on composite scales(anxiety, insomnia and drive), and on four core subscales that capture core depression symptoms.RESULTS: There was a significantly greater decrease in MADRS scores in aripiprazole group compared to bupropion group at 4(p<0.05) and 6(p<0.05) weeks. There were significantly higher response rate at week 4(p<0.05) and 6(p<0.05) and remission rate at week 6 in aripiprazole group compared to bupropion group. Individual HAM-D17 items showing significantly greater change with adjunctive aripiprazole than bupropion: insomnia, late(ES=0.81 vs. −0.24, p=0.043), psychomotor retardation(ES=1.30 vs. 0.66, p=0.024), general somatic symptoms(ES=1.24 vs. 0.00, p=0.01). On three composite scales, adjunctive aripiprazole was significantly more effective than bupropion with respect to mean change for drive(p=0.005).CONCLUSION: Results of this study suggested that aripiprazole augmentation have superior efficacy in treating general and core symptoms of depression in older adult patients. Aripiprazole augmentation is associated with greater improvement in specific symptoms of depression such as psychomotor retardation, general somatic symptoms and drive.
Adult ; Aripiprazole ; Bupropion ; Depression ; Depressive Disorder, Major ; Fatigue ; Humans ; Iowa ; Prospective Studies ; Serotonin ; Sleep Initiation and Maintenance Disorders ; Weights and Measures

Eosinophils have long been recognized as a central effector cell in the lungs of asthmatic patients. They contribute to airway inflammation and remodeling through releasing several molecules such as cytokines, granule proteins, lipid mediators and extracellular traps/vesicles. Repeated evidence reveals that intense eosinophil infiltration in upper and lower airway mucosae contributes to the pathogenesis of aspirin-exacerbated respiratory disease (AERD). Persistent eosinophilia is found to be associated with type 2 immune responses, cysteinyl leukotriene overproduction and eosinophil-epithelium interactions. This review highlights recent findings about key mechanisms of eosinophil activation in the airway inflammation of AERD. In addition, current biologics (targeting type 2 immune responses) were suggested to control eosinophilic inflammation for AERD patients.