Background/Aims: Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis. Methods: Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to timeof-flight mass spectrometry. Correlation analyses were performed targeting the gut-microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased). Results: Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC >0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites. Conclusions Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.

Background: Perioperative adverse cardiac events (PACE), a composite of myocardial infarction, coronary revascularization, congestive heart failure, arrhythmic attack, acute pulmonary embolism, cardiac arrest, and stroke during 30-day postoperative period, is associated with long-term mortality, but with limited clinical evidence. We compared long-term mortality with PACE using data from nationwide multicenter electronic health records. Methods: Data from 7 hospitals, converted to Observational Medical Outcomes Partnership Common Data Model, were used. We extracted records of 277,787 adult patients over 18 years old undergoing non-cardiac surgery for the first time at the hospital and had medical records for more than 180 days before surgery. We performed propensity score matching and then an aggregated meta‑analysis. Results: After 1:4 propensity score matching, 7,970 patients with PACE and 28,807 patients without PACE were matched. The meta‑analysis showed that PACE was associated with higher one-year mortality risk (hazard ratio [HR]: 1.33, 95% CI [1.10, 1.60], P = 0.005) and higher three-year mortality (HR: 1.18, 95% CI [1.01, 1.38], P = 0.038). In subgroup analysis, the risk of one-year mortality by PACE became greater with higher-risk surgical procedures (HR: 1.20, 95% CI [1.04, 1.39], P = 0.020 for low-risk surgery; HR: 1.69, 95% CI [1.45, 1.96], P < 0.001 for intermediate-risk; and HR: 2.38, 95% CI [1.47, 3.86], P = 0.034 for high-risk). Conclusions A nationwide multicenter study showed that PACE was significantly associated with increased one-year mortality. This association was stronger in high-risk surgery, older, male, and chronic kidney disease subgroups. Further studies to improve mortality associated with PACE are needed.

Background/Aims: The prospective Crohn’s Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn’s disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD. Methods: Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019). Results: A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p<0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35;95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection. Conclusions The prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal resection.

Background: and Purpose Oral administration of cholinesterase inhibitors is often associated with adverse gastrointestinal effects, and so developing an alternative administration route, such as transdermal, is urgently needed. The primary objective of this study was to determine the efficacy and safety of the IPI-301 donepezil transdermal patch compared with donepezil tablets (control) in mild-to-moderate probable Alzheimer’s disease (AD). Methods: This prospective, randomized, double-blind, double-dummy, two-arm parallel, multicenter trial included 399 patients, among whom 303 completed the trial. For randomization, the patients were stratified based on previous treatment and donepezil dose; patients in each stratum were randomized to the test and control groups at a 1:1 ratio. Results: The difference between the control group and the IPI-301 group, quantified as the Hodges–Lehmann estimate of location shift, was 0.00 (95% confidence interval: -1.00 to 1.33), with an upper limit of less than 2.02. The change in Alzheimer’s Disease Cooperative Study– Activities of Daily Living (ADCS-ADL) score differed significantly between the IPI-301 and control groups (p=0.02). However, the changes in the full-itemized ADCS-ADL scores at week 24 did not differ significantly between the two groups. There were no differences between the two groups regarding the scores for the Clinician Interview-Based Impression of Change (f0.9097), Mini-Mental State Examination (p=0.7018), Neuropsychiatric Inventory (p=0.7656), or Clinical Dementia Rating (p=0.9990). Adverse events, vital signs, and laboratory test results were comparable between the two groups. Conclusions IPI-301 was safe and efficacious in improving cognitive function in patients with mild-to-moderate AD.

Objective: The risk of suicide is assessed by identifying the relationship between alcohol-use patterns and suicidal ideation in Korean employees. Methods: The study involved 13,858 employees who underwent workplace mental health screening at the Workplace Mental Health Institute of Kangbuk Samsung Hospital over a 6-year period between 2014 and 2019. Analysis was performed separately for Alcohol Use Disorders Identification Test-Korea (AUDIT-K) items related to the frequency/volume of alcohol consumption (items 1 to 3, AUDIT-C) and those regarding alcohol dependence/related problems (items 4 to 10, AUDIT-D/P). Subjects were then classified into three groups on the basis of the presence or absence of clinical depression and suicidal ideation. The groups’ sociodemographic factors and clinical features of depression, anxiety, and alcohol-use patterns were analyzed with a chi-square test as well as one-way analysis of variance, followed by a post hoc test using the Bonferroni correction. Results: AUDIT-K and AUDIT-D/P scores were significantly associated with the presence or absence of clinical depression as well as the presence or absence of suicidal ideation (p<0.05). However, no significant differences were found among the three groups with regard to the AUDIT-C score (p=0.054). Conclusion Identifying or treating alcohol dependence/related problems can help lower the occurrence of mental health problems, and suicidal ideation in particular, in employees and reduce social costs.

BACKGROUND: This study aimed to evaluate the effect of cervical cerclage on the recurrence risk for preterm birth in singleton pregnant women after a twin spontaneous preterm birth (sPTB).METHODS: This multicenter retrospective cohort study included women who had a singleton pregnancy from January 2009 to December 2018 at 10 referral hospitals and a twin sPTB before the current pregnancy. We compared the cervical lengths during pregnancy and pregnancy outcomes, according to the placement of prophylactic or emergency cerclage. We evaluated the independent risk factors for sPTB (< 37 weeks of gestation) in a subsequent singleton pregnancy.RESULTS: For the index singleton pregnancy, preterm birth occurred in seven (11.1%) of 63 women. There was no significant difference in the cervical lengths during pregnancy in women with and without cerclage. In a multivariate logistic regression analysis, the placement of emergency cerclage was an independent risk factor for subsequent singleton preterm birth (odds ratio [OR], 93.188; 95% confidence interval [CI], 1.633–5,316.628; P = 0.027); however, the placement of prophylactic cerclage (OR, 19.264; 95% CI, 0.915–405.786; P = 0.057) was not a factor. None of the women who received prophylactic cerclage delivered before 35 weeks' gestation in the index singleton pregnancy.CONCLUSION: Cerclage did not lower the risk of preterm birth in a subsequent singleton pregnancy after a twin sPTB. However, emergency cerclage was an independent risk factor for preterm birth and there was no preterm birth before 35 weeks' gestation in the prophylactic cerclage group. Therefore, close monitoring of the cervical length and prophylactic cerclage might be considered in women who have experienced a twin sPTB at extreme gestation.

BACKGROUND: This study aimed to evaluate the effect of cervical cerclage on the recurrence risk for preterm birth in singleton pregnant women after a twin spontaneous preterm birth (sPTB). METHODS: This multicenter retrospective cohort study included women who had a singleton pregnancy from January 2009 to December 2018 at 10 referral hospitals and a twin sPTB before the current pregnancy. We compared the cervical lengths during pregnancy and pregnancy outcomes, according to the placement of prophylactic or emergency cerclage. We evaluated the independent risk factors for sPTB (< 37 weeks of gestation) in a subsequent singleton pregnancy. RESULTS: For the index singleton pregnancy, preterm birth occurred in seven (11.1%) of 63 women. There was no significant difference in the cervical lengths during pregnancy in women with and without cerclage. In a multivariate logistic regression analysis, the placement of emergency cerclage was an independent risk factor for subsequent singleton preterm birth (odds ratio [OR], 93.188; 95% confidence interval [CI], 1.633–5,316.628; P = 0.027); however, the placement of prophylactic cerclage (OR, 19.264; 95% CI, 0.915–405.786; P = 0.057) was not a factor. None of the women who received prophylactic cerclage delivered before 35 weeks' gestation in the index singleton pregnancy. CONCLUSION Cerclage did not lower the risk of preterm birth in a subsequent singleton pregnancy after a twin sPTB. However, emergency cerclage was an independent risk factor for preterm birth and there was no preterm birth before 35 weeks' gestation in the prophylactic cerclage group. Therefore, close monitoring of the cervical length and prophylactic cerclage might be considered in women who have experienced a twin sPTB at extreme gestation.

PURPOSE: Lung Cancer Subcommittee of Korean Radiation Oncology Group (KROG) has recently launched a prospective clinical trial (KROG 17-06) of hippocampus-sparing whole brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) in treating multiple brain metastases from non-small cell lung cancer. In order to improve trial quality, dummy run studies among the participating institutions were designed. This work reported the results of two-step dummy run procedures of the KROG 17-06 study. MATERIALS AND METHODS: Two steps tested hippocampus contouring variability and radiation therapy planning compliance. In the first step, the variation of the hippocampus delineation was investigated for two representative cases using the Dice similarity coefficients. In the second step, the participating institutions were requested to generate a HS-WBRT with SIB treatment plan for another representative case. The compliance of the treatment plans to the planning protocol was evaluated. RESULTS: In the first step, the median Dice similarity coefficients of the hippocampus contours for two other dummy run cases changed from 0.669 (range, 0.073 to 0.712) to 0.690 (range, 0.522 to 0.750) and from 0.291 (range, 0.219 to 0.522) to 0.412 (range, 0.264 to 0.598) after providing the hippocampus contouring feedback. In the second step, with providing additional plan priority and extended dose constraints to the target volumes and normal structures, we observed the improved compliance of the treatment plans to the planning protocol. CONCLUSION: The dummy run studies demonstrated the notable inter-institutional variability in delineating the hippocampus and treatment plan generation, which could be decreased through feedback from the trial center.
Brain ; Carcinoma, Non-Small-Cell Lung ; Compliance ; Hippocampus ; Lung Neoplasms ; Neoplasm Metastasis ; Prospective Studies ; Radiation Oncology ; Radiotherapy

PURPOSE: Respiratory syncytial virus (RSV) infection can cause various neurological complications. This study aimed to investigate the RSV-associated neurologic manifestations that present with seizures. METHODS: We retrospectively reviewed the medical records of patients aged less than 15 years with laboratory-confirmed RSV infections and seizures between January 2011 and December 2016 in a regional hospital in South Korea. RESULTS: During this period, 1,193 patients with laboratory-confirmed RSV infection were identified. Of these, 35 (35 of 1,193, 2.93%; boys, 19; girls, 16; mean age: 20.8±16.6 months) presented with seizure. Febrile seizure was the most common diagnosis (27 of 35, 77.1%); simple febrile seizures in 13 patients (13 of 27, 48.1%) and complex febrile seizures in 14 (14 of 27, 51.9%). Afebrile seizures without meningitis or encephalopathy were observed in 5 patients (5 of 35, 14.3%), seizures with meningitis in 2 (2 of 35, 5.7%), and seizure with encephalopathy in 1 (1 of 35, 2.9%) patient. Lower respiratory symptoms were not observed in 8 patients. In a patient with encephalopathy, brain diffusion-weighted magnetic resonance imaging revealed transient changes in white matter, suggesting cytotoxic edema as the mechanism underlying encephalopathy. Most patients recovered with general management, and progression to epilepsy was noted in only 1 patient. CONCLUSION: Although febrile seizures are the most common type of seizure associated with RSV infection, the proportion of patients with complex febrile seizures was higher than that of those with general febrile seizures. Transient cytotoxic edema may be a pathogenic mechanism in RSV-related encephalopathy with seizures.
Brain ; Brain Diseases ; Child ; Diagnosis ; Edema ; Epilepsy ; Female ; Humans ; Korea ; Magnetic Resonance Imaging ; Medical Records ; Meningitis ; Neurologic Manifestations ; Respiratory Syncytial Viruses ; Retrospective Studies ; Seizures ; Seizures, Febrile ; White Matter

BACKGROUND AND PURPOSE: Visual assessment of medial temporal-lobe atrophy (MTA) has been quick, reliable, and easy to apply in routine clinical practice. However, one of the limitations in visual assessments of MTA is the lack of widely accepted age-adjusted norms and cutoff scores for MTA for a diagnosis of Alzheimer's disease (AD). This study aimed to determine the optimal cutoff score on a T1-weighted axial MTA Visual Rating Scale (VRS) for differentiating patients with AD from cognitively normal elderly people. METHODS: The 3,430 recruited subjects comprising 1,427 with no cognitive impairment (NC) and 2003 AD patients were divided into age ranges of 50–59, 60–69, 70–79, and 80–89 years. Of these, 446 participants (218 in the NC group and 228 in the AD group) were chosen by random sampling for inclusion in this study. Each decade age group included 57 individuals, with the exception of 47 subjects being included in the 80- to 89-year NC group. The scores on the T1-weighted axial MTA VRS were graded by two neurologists. The cutoff values were evaluated from the area under the receiver operating characteristic curve. RESULTS: The optimal axial MTA VRS cutoff score from discriminating AD from NC increased with age: it was ≥as ≥1, ≥2, and ≥3 in subjects aged 50–59, 60–69, 70–79, and 80–89 years, respectively (all p < 0.001). CONCLUSIONS: These results show that the optimal cutoff score on the axial MTA VRS for diagnosing of AD differed according to the decade age group. This information could be of practical usefulness in the clinical setting.
Aged ; Alzheimer Disease* ; Atrophy* ; Cognition Disorders ; Dementia* ; Diagnosis ; Humans ; Korea* ; Pemetrexed ; ROC Curve