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: and Purpose Unlike other immune-mediated neuropathies, anti-myelin-associated glycoprotein (MAG) neuropathy is often refractory to immunotherapy. It is necessary to compare the relative efficacies of various immunotherapies and develop objective biomarkers in order to optimize its clinical management. Methods: This study recruited 91 patients with high anti-MAG antibody titers from 7 tertiary hospitals in South Korea. We analyzed the baseline characteristics, therapeutic outcomes, and nerve conduction study (NCS) findings of 68 patients and excluded 23 false positive cases. Results: The rate of positive responses to treatment was highest using zanubrutinib (50%) and rituximab (36.4%), followed by corticosteroids (16.7%), immunosuppressants (9.5%), intravenous immunoglobulin (5%), and plasma exchange (0%). Disability and weakness were significantly associated with multiple NCS parameters at the time of diagnosis, especially distal compound muscle action potential (CMAP) amplitudes. Moreover, the longitudinal trajectory of the average CMAP amplitudes paralleled the clinical courses, with a 16.2 percentile decrease as an optimal cutoff for predicting a clinical exacerbation (area under the receiver operating characteristic curve=0.792). Conclusions Our study supports the use of NCS as an objective marker for estimating disease burden and tracking clinical changes in patients with anti-MAG neuropathy. We have described the beneficial effects of rituximab and a new drug, zanubrutinib, compared with conventional immunotherapies.

Background: The gut–brain axis (GBA) in Parkinson’s disease (PD) has only been investigated in limited mice models despite dysbiosis of the gut microbiota being considered one of the major treatment targets for neurodegenerative disease. Therefore, this study examined the compositional changes of fecal microbiota in novel transgenic (Tg) mice overexpressing human α-synuclein (hαSyn) proteins under the neuron-specific enolase (NSE) to analyze the potential as GBA model. Results: The expression level of the αSyn proteins was significantly higher in the substantia nigra and striatum of NSEhαSyn Tg mice than the Non-Tg mice, while those of tyrosine hydroxylase (TH) were decreased in the same group. In addition, a decrease of 72.7% in the fall times and a 3.8-fold increase in the fall number was detected in NSE-hαSyn Tg mice. The villus thickness and crypt length on the histological structure of the gastrointestinal (GI) tract decreased in NSE-hαSyn Tg mice. Furthermore, the NSE-hαSyn Tg mice exhibited a significant increase in 11 genera, including Scatolibacter, Clostridium, Feifania, Lachnoclostridium, and Acetatifactor population, and a decrease in only two genera in Ligilactobacillus and Sangeribacter population during enhancement of microbiota richness and diversity. Conclusions The motor coordination and balance dysfunction of NSE-hαSyn Tg mice may be associated with compositional changes in gut microbiota. In addition, these mice have potential as a GBA model.

Purpose: We performed this study to determine whether the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker of individual susceptibility to chemotherapeutic agents affecting treatment outcome in patients with neuroblastoma. Materials and Methods: The study included 313 patients who received the first cycle chemotherapy with a CEDC (cisplatin+etoposide+doxorubicin+cyclophosphamide) regimen and had absolute neutrophil count (ANC) data available. The cumulative incidences of progression and treatment-related mortality (TRM) were estimated. To identify genetic variations associated with the ANC, a genome-wide association study (GWAS) was performed. Results: An ANC of 32.5/μL was determined as the cutoff point to categorize patients into the good and poor prognosis subgroups in terms of progression. Patients with a high nadir ANC had a higher cumulative incidence of progression than those with a low nadir ANC (p < 0.001). In multivariate analysis, high nadir ANC, age, bone marrow involvement, and unfavorable histology were poor prognostic factors. With regard to the TRM, patients with a low nadir ANC (ANC < 51.0/μL) had a higher cumulative incidence of TRM than those with a high nadir ANC (p=0.010). In GWAS, single-nucleotide polymorphisms of LPHN2 and CRHR1 were significantly associated with the nadir ANC. Conclusion In neuroblastoma patients, the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker to predict an individual’s susceptibility to chemotherapeutic agents. Tailoring of treatment based on the degree of neutropenia needs to be considered.

Purpose: Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas. Materials and Methods: To address such challenges, we have developed a glioma-specific NGS panel, termed “GliomaSCAN,” that is capable of capturing single nucleotide variations and insertion/deletion, copy number variation, and selected promoter mutations and structural variations that cover a subset of intron regions in 232 essential glioma-associated genes. We confirmed clinical concordance rate using pairwise comparison of the identified variants from whole exome sequencing (WES), immunohistochemical analysis, and fluorescence in situ hybridization. Results: Our panel demonstrated high sensitivity in detecting potential genomic variants that were present in the standard materials. To ensure the accuracy of our targeted sequencing panel, we compared our targeted panel to WES. The comparison results demonstrated a high correlation. Furthermore, we evaluated clinical utility of our panel in 46 glioma patients to assess the detection capacity of potential actionable mutations. Thirty-two patients harbored at least one recurrent somatic mutation in clinically actionable gene. Conclusion We have established a glioma-specific cancer panel. GliomaSCAN highly excelled in capturing somatic variations in terms of both sensitivity and specificity and provided potential clinical implication in facilitating genome-based clinical trials. Our results could provide conceptual advance towards improving the response of genomically guided molecularly targeted therapy in glioma patients.

BACKGROUND/AIMS: It is well known that gender differences are associated with clinical outcomes in patients with acute myocardial infarction (AMI). However, it is not clear whether gender differences affect the prognosis of elderly patients with AMI. METHODS: We analyzed the incidence of in-hospital complications and mortality in the Korea Acute Myocardial Infarction Registry-National Institutes of Health from November 2011 to June 2015. This study included elderly patients (≥ 75 years) diagnosed with AMI. RESULTS: A total of 2,953 patients were eligible for this study. Among them, 1,529 (51.8%) patients were female, and the mean age of the female group was older than that of the male group (80.7 ± 4.4 vs. 79.6 ± 4.0 years, respectively, p < 0.001). Elderly females utilized emergency medical services less frequently compared with elderly males (11.5 vs. 15.4%, respectively, p < 0.001). Elderly female AMI patients had a similar rate of in-hospital mortality compared with elderly males (7.1 vs. 8.4%, respectively, p = 0.196). The rate of major cardiac adverse events (MACEs) was lower in elderly females than males during a 12-month follow-up (hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.00-1.41, p = 0.045). According to multivariate analysis, the male gender is an independent factor for predicting 1-year MACEs (HR 1.37, 95% CI 1.14-1.65, p < 0.001). CONCLUSIONS: No significant differences in peri-procedural complications or in-hospital mortality were observed between male and female elderly patients with AMI. However, elderly female patients had a more favorable prognosis than male patients during a 1-year clinical follow-up.
Academies and Institutes ; Aged ; Emergency Medical Services ; Female ; Follow-Up Studies ; Hospital Mortality ; Humans ; Incidence ; Korea ; Male ; Mortality ; Multivariate Analysis ; Myocardial Infarction ; Prognosis

PURPOSE: The diagnostic criteria of gastric intraepithelial neoplasia (IEN) are controversial across the world. We investigated how many discrepancies occur in the pathologic diagnosis of IEN and early gastric carcinoma in endoscopic submucosal dissection (ESD) specimens, and evaluated the reasons of the discordance. MATERIALS AND METHODS: We retrospectively reviewed 1,202 ESD specimens that were originally diagnosed as gastric IEN and early carcinoma at 12 institutions. RESULTS: The final consensus diagnosis of carcinoma were 756 cases, which were originally 692 carcinomas (91.5%), 43 high-grade dysplasias (5.7%), 20 low-grade dysplasias (2.6%), and 1 others (0.1%), respectively. High- and low-grade dysplasia were finally made in 63 and 342 cases, respectively. The diagnostic concordance with the consensus diagnosis was the highest for carcinoma (91.5%), followed by low-grade dysplasia (86.3%), others (63.4%) and high-grade dysplasia (50.8%). The general kappa value was 0.83, indicating excellent concordance. The kappa values of individual institutions ranged from 0.74 to 1 and correlated with the proportion of carcinoma cases. The cases revised to a final diagnosis of carcinoma exhibited both architectural abnormalities and cytologic atypia. The main differential points between low- and high-grade dysplasias were the glandular distribution and glandular shape. Additional features such as the glandular axis, surface maturation, nuclear stratification and nuclear polarity were also important. CONCLUSION: The overall concordance of the diagnosis of gastric IEN and early carcinoma in ESD specimens was excellent. It correlated with the proportion of carcinoma cases, demonstrating that the diagnostic criteria for carcinoma are more reproducible than those for dysplasia.
Consensus ; Diagnosis ; Retrospective Studies ; Stomach Neoplasms

BACKGROUND: Recent evidences indicate that early rapid renal function decline is closely associated with the development and progression of diabetic kidney disease. We have investigated the association between carotid atherosclerosis and rapid renal function decline in patients with type 2 diabetes mellitus and preserved renal function.METHODS: In a prospective, multicenter cohort, a total of 967 patients with type 2 diabetes mellitus and preserved renal function were followed for 6 years with serial estimated glomerular filtration rate (eGFR) measurements. Common carotid intima-media thickness (CIMT) and presence of carotid plaque were assessed at baseline. Rapid renal function decline was defined as an eGFR decline >3.3% per year.RESULTS: Over a median follow-up of 6 years, 158 participants (16.3%) developed rapid renal function decline. While there was no difference in CIMT, the presence of carotid plaque in rapid decliners was significantly higher than in non-decliners (23.2% vs. 12.2%, P<0.001). In multivariable logistic regression analysis, presence of carotid plaque was an independent predictor of rapid renal function decline (odds ratio, 2.33; 95% confidence interval, 1.48 to 3.68; P<0.0001) after adjustment for established risk factors. The model including the carotid plaque had better performance for discrimination of rapid renal function decline than the model without carotid plaque (area under the receiver operating characteristic curve 0.772 vs. 0.744, P=0.016).CONCLUSION: Close monitoring of renal function and early intensive management may be beneficial in patients with type 2 diabetes mellitus and carotid plaques.
Carotid Artery Diseases ; Carotid Intima-Media Thickness ; Carotid Stenosis ; Cohort Studies ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Discrimination (Psychology) ; Follow-Up Studies ; Glomerular Filtration Rate ; Humans ; Logistic Models ; Prospective Studies ; Risk Factors ; ROC Curve

BACKGROUND/AIMS: It is well known that gender differences are associated with clinical outcomes in patients with acute myocardial infarction (AMI). However, it is not clear whether gender differences affect the prognosis of elderly patients with AMI. METHODS: We analyzed the incidence of in-hospital complications and mortality in the Korea Acute Myocardial Infarction Registry-National Institutes of Health from November 2011 to June 2015. This study included elderly patients (≥ 75 years) diagnosed with AMI. RESULTS: A total of 2,953 patients were eligible for this study. Among them, 1,529 (51.8%) patients were female, and the mean age of the female group was older than that of the male group (80.7 ± 4.4 vs. 79.6 ± 4.0 years, respectively, p < 0.001). Elderly females utilized emergency medical services less frequently compared with elderly males (11.5 vs. 15.4%, respectively, p < 0.001). Elderly female AMI patients had a similar rate of in-hospital mortality compared with elderly males (7.1 vs. 8.4%, respectively, p = 0.196). The rate of major cardiac adverse events (MACEs) was lower in elderly females than males during a 12-month follow-up (hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.00-1.41, p = 0.045). According to multivariate analysis, the male gender is an independent factor for predicting 1-year MACEs (HR 1.37, 95% CI 1.14-1.65, p < 0.001). CONCLUSIONS No significant differences in peri-procedural complications or in-hospital mortality were observed between male and female elderly patients with AMI. However, elderly female patients had a more favorable prognosis than male patients during a 1-year clinical follow-up.

BACKGROUND/AIMS: Several previous studies suggest that eradication of Helicobacter pylori (H. pylori) leads to the disappearance of gastric hyperplastic polyps. However, little is known about the effect of H. pylori status and eradication on the recurrence of gastric polyps after endoscopic removal. Here, we investigated the recurrence of gastric polyps according to the final H. pylori status in patients who underwent endoscopic removal of gastric hyperplastic polyps. METHODS: Between January 2011 and December 2016, patients who underwent endoscopic removal of gastric hyperplastic polyps and were followed-up for more than two months were enrolled. The success of H. pylori eradication was assessed by histology and rapid urease test or urea breath test, at least 4 weeks after the completion of eradication treatment. At follow-up, the recurrence of gastric polyp was evaluated via esophagogastroduodenoscopy. RESULTS: Seventy-nine patients were enrolled. During the mean follow-up period of 16.4 months, the recurrence rate of gastric polyp was 25.3%. Among those who received H. pylori eradication therapy, the H. pylori persistent group showed a higher recurrence of polyp than the H. pylori eradicated group; but there was no statistical significance (42.9% vs. 21.7%, p=0.269). Regarding the final H. pylori infection status, the recurrence rate of gastric polyps was significantly higher in the H. pylori positive group than in the H. pylori negative group (42.9% vs. 18.9%, p=0.031). In multivariate analysis, the final H. pylori infection status was a significant risk factor for gastric polyp recurrence after endoscopic removal. CONCLUSIONS: The final positive H. pylori infection status is significantly associated with higher recurrence of gastric hyperplastic polyps after endoscopic removal.
Breath Tests ; Endoscopy, Digestive System ; Follow-Up Studies ; Helicobacter pylori* ; Helicobacter* ; Humans ; Multivariate Analysis ; Polyps* ; Recurrence* ; Risk Factors ; Stomach Neoplasms ; Urea ; Urease