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Background/Aims: Fexuprazan is a novel potassium-competitive acid blocker that could be of benefit to patients with gastric mucosal injury. The aim of this study was to assess the 2-week efficacy and safety of fexuprazan in patients with acute or chronic gastritis.Methods: In this study, 327 patients with acute or chronic gastritis who had one or more gastric erosions on endoscopy and subjective symptoms were randomized into three groups receiving fexuprazan 20 mg once a day (q.d.), fexuprazan 10 mg twice a day (b.i.d.), or placebo for 2 weeks. The posttreatment assessments were the primary endpoint (erosion improvement rate), secondary endpoints (cure rates of erosion and edema and improvement rates of redness, hemorrhage, and subjective symptoms), and drug-related adverse events.Results: Among the patients, 57.8% (59/102), 65.7% (67/102), and 40.6% (39/96) showed erosion improvement 2 weeks after receiving fexuprazan 20 mg q.d., fexuprazan 10 mg b.i.d., and placebo, respectively. Both fexuprazan 20 mg q.d. and 10 mg b.i.d. showed superior efficacy to the placebo (p=0.017 and p

Background/Aims Metachronous recurrence incidences and risk factors following endoscopic submucosal dissection (ESD) for gastric adenocarcinoma and dysplasias were investigated. Methods Retrospective review of electronic medical records of patients who underwent gastric ESD at The Catholic University of Korea, Yeouido St. Mary’s Hospital. Results A total of 190 subjects were enrolled for analysis during the study period. The mean age was 64.4 years-old and the male sex occupied 73.7%. The mean observation period following ESD was 3.45 years. The annual incidence rate of metachronous gastric neoplasms (MGN) was about 3.96%. The annual incidence rate was 5.36% for the low-grade dysplasia group, 6.47% for the high-grade dysplasia group, and 2.74% for the EGC group. MGN was more frequent in the dysplasia group than in the EGC group (p

This paper reports a 70-year-old female with gastric extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (gastric MALT lymphoma) as a rare case of gastric outlet obstruction. Five years earlier, she initially presented with weight loss and anemia. Esophagogastroduodenoscopy (EGD) revealed multiple gastric and duodenal ulcers with a pyloric deformity, while histology revealed chronic active inflammation and a Helicobacter pylori (H. pylori) infection. Three years earlier, she underwent EGD per the National Cancer Screening Program and was diagnosed with antral and duodenal ulcers. A forceps biopsy specimen from one of the ulcers showed the findings of gastric MALT lymphoma, but she did not visit the hospital for proper management. She visited complaining of a loss of appetite. EGD revealed a gastric outlet obstruction (GOO) caused by antral deformity and pyloric narrowing. A staged workup with CT and PET revealed full-layered, encircling antral wall thickening and several enlarged mesenteric lymph nodes. She was finally diagnosed with a gastric MALT lymphoma at Ann Arbor stage I1E with translocation t(11;18). She was treated with palliative surgery for GOO and systemic chemotherapy with a CHOP regimen. This paper reports a gastric MALT lymphoma that progressed from superficial mucosal lesions to an overt mass with regional lymph node metastasis for five years.

Abstract Background Identifying clarithromycin resistance is essential for eradicating Helicobacter pylori (HP). Therefore, we evaluated the performance of Allplex™ H.pylori & ClariR Assay (Allplex™) for diagnosing and detecting clarithromycin resistance in HP. Methods Subjects who underwent esophagogastroduodenoscopy between April 2020 and August 2021 at Incheon St. Mary’s hospital were enrolled in this study. The diagnostic performances of Allplex™ and dual priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) were compared with sequencing as the gold standard. Results A total of 142 gastric biopsy samples were analyzed. Gene sequencing revealed 124 HP infections, 42 A2143G mutations, 2 A2142G mutations, one dual mutation, and no A2142C mutation. DPO-PCR showed 96.0% sensitivity and 100.0% specificity for HP detection; the corresponding rates for Allplex™ were 99.2% and 100.0%. DPO-PCR showed 88.3% sensitivity and 82.0% specificity for A2143G mutation, and Allplex™ showed 97.6% and 96.0%. The Cohen’s Kappa coefficient for overall test results was 0.56 for DPO-PCR and 0.95 for Allplex™. Conclusion Allplex™ showed comparable diagnostic performance with direct gene sequencing and non-inferior diagnostic performance to DPO-PCR. Further research is required to confirm whether Allplex™ is an effective diagnostic tool for the eradication of HP.

Abstract Background Bismuth salt is bacteriostatic and bactericidal against Helicobacter pylori (H. pylori). Little is known about the benefit of bismuth itself. Recently in Korea, government regulation changed to allow bismuth add-on to conventional triple eradication regimens. Study aimed the additional benefit of the bismuth add-on to the 2-week clarithromycin-based triple regimen for H. pylori eradication. Methods A single-centered retrospective review of electronic medical records was conducted in Seoul, Korea. Treatment-naïve H. pylori infected subjects treated with the clarithromycin-based triple regimen were consecutively enrolled. After propensity score matching, 118 subjects who were treated with rabeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for 14 days (PAC) and matched 118 subjects with PAC plus bismuth subcitrate potassium 300 mg twice daily for 14 days (PACB) were included in the final analysis. The primary endpoint was the eradication success rates in each group.Article title: Kindly check and confirm the edit made in the article title.Yes, I agree with the article title. Results The eradication success rates were 91.5% (86.4–96.6%) for PACB regimen and 81.4% (74.2–88.5%) for PAC in the intention-to-treat analysis, and 97.3% (94.2–100%) for PACB and 88.1% (81.9–94.3%) for PAC in the per-protocol analysis. The relative risk of eradication failure for PACB over PAC was calculated as 0.184 (0.0492–0688, p value = 0.005) in multiple regression logistic analysis. Compliance and adverse event incidence were not different between the two groups.Author names: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [Da Wit], Last name: [Shin]. Author 2 Given name: [Dae Young], Last name: [Cheung]. Author 3 Given name: [Ji Hee], Last name: [Song]. Author 4 Given name: [Fan Hee], Last name: [Lee]. Author 5 Given name: [Jin Il], Last name: [Kim]. Yes. I found the names presented are accurate and in the correct sequence. Author 1 Given name: [Da Wit], Last name: [Shin].Author 2 Given name: [Dae Young], Last name: [Cheung].Author 3 Given name: [Ji Hee], Last name: [Song].Author 6 Given name: [Han Hee], Last name: [Lee].Author 7 Given name: [Jin Il], Last name: [Kim]. Conclusion The bismuth add-on to the 2-week clarithromycin-based triple regimen increased the eradication success rate.

BackgroundSevere fever with thrombocytopenia syndrome virus (SFTSV) is a viral pathogen causing significant clinical signs from mild fever with thrombocytopenia to severe hemorrhages. World Health Organization has paid special attention to the dramatic increase in human SFTS cases in China, Japan, and South Korea since the 2010s. The present study investigated the molecular evolution and genetic reassortment of SFTSVs using complete genomic sequences.Methods/principal findingWe collected the complete genome sequences of SFTSVs globally isolated until 2019 (L segment, n = 307; M segment, n = 326; and S segment, n = 564) and evaluated the evolutionary profiles of SFTSVs based on phylogenetic and molecular selection pressure analyses. By employing a time-scaled Bayesian inference method, we found the geographical heterogeneity of dominant SFTSV genotypes in China, Japan, and South Korea around several centuries before and locally spread by tick-born spillover with infrequent long-distance transmission. Purifying selection predominated the molecular evolution of SFTSVs with limited gene reassortment and fixed substitution, but almost all three gene segments appeared to harbor at least one amino acid residue under positive selection. Specifically, the nonstructural protein and glycoprotein (Gn/Gc) genes were preferential selective targets, and the Gn region retained the highest number of positively selected residues.Conclusion/significanceHere, the large-scale genomic analyses of SFTSVs improved prior knowledge of how this virus emerged and evolved in China, Japan, and South Korea. Our results highlight the importance of SFTSV surveillance in both human and non-human reservoirs at the molecular level to fight against fatal human infection with the virus.

Summary: SARS-CoV-2 variants have continuously emerged globally, including in South Korea. To characterize the molecular evolution of SARS-CoV-2 in South Korea, we performed phylogenetic and genomic recombination analyses using more than 12,000 complete genome sequences collected until October 2022. The variants in South Korea originated from globally identified variants of concern and harbored genetic clade-common and clade-specific amino acid mutations mainly around the N-terminal domain (NTD) or receptor binding domain (RBD) in the spike protein. Several point mutation residues in key antigenic sites were under positive selection persistently with changing genetic clades of SARS-CoV-2. Furthermore, we detected 17 potential genomic recombinants and 76.4% (13/17) retained the mosaic NTD or RBD genome. Our results suggest that point mutations and genomic recombination in the spike contributed to the molecular evolution of SARS-CoV-2 in South Korea, which will form an integral part of global prevention and control measures against SARS-CoV-2.

Background/Aims: The gastric extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (gastric MALT lymphoma) are mostly related to Helicobacter pylori infections. However, chromosomal aberration involving translocation t(11;18) is also frequently reported in these patients. Methods: The study was a retrospective review and analysis of electronic medical records to assess the factors which affect complete remission (CR) in patients with gastric MALT lymphoma. Based on the medical records, subjects with gastric MALT lymphoma were enrolled consecutively from January 2004 to December 2021. Results: Among the 77 subjects who were found with gastric MALT lymphoma in the database, 65 cases with complete records were analyzed. Of these, 66.2% (43/65) were H. pylori positive. Genetic analyses for t(11:18) were done on 41 subjects. The t(11:18) chromosomal translocation with MALT1:BIRC3 fusion was found in 31.7% (13/41) of the subjects. With H. pylori eradication therapy, 75% (21/28) of the subjects without t(11:18) achieved CR. However, only 23.1% (3/13) subjects with t(11:18) could achieve CR (p-value= 0.009). In the H. pylori-positive group, 85.7% (18/21) subjects without t(11:18) achieved CR with eradication therapy, but 71.4% (5/7) subjects with t(11:18) failed to achieve CR (p-value=0.004). In the H. pylori-negative group, 42.3% (3/7) of the subjects without t(11:18) achieved CR with eradication therapy. However, 83.3% (5/6) of H. pylori-negative subjects with t(11:18) failed to achieve CR with eradication therapy and needed additional radiotherapy (p-value=0.396). Conclusions: H. pylori negativity and the presence of t(11:18) were both risk factors for failure to achieve CR with H. pylori eradication therapy as the first line of treatment.

Background/Aims Recent epidemiologic studies have shown a continued increase in colorectal cancer incidence among younger adults. Little is known about the factors that contribute to the development of young-onset colorectal neoplasia (CRN). Methods A cross-sectional analysis was performed for individuals younger than 40 years who underwent colonoscopy in Seoul St. Mary’s Hospital and its affiliated health screening center. High-risk CRN was defined as adenoma or sessile serrated lesion ≥ 10 mm, with three or more adenomas, villous histology, high grade dysplasia, or carcinoma. Results Of these 13,621 included participants, 2,023 (14.9%) had one and more CRN. Young patients with CRN tended to be elderly, male, obese, smoker, having a habit of drinking, and having comorbidities such as hypertension, dyslipidemia, diabetes, and chronic kidney disease. In a multivariate analysis adjusted for age, sex, obesity, smoking status, and alcohol intake, old age (odds ratio [OR], 1.086; 95% confidence interval [CI], 1.054 to 1.119), male sex (OR, 1.748; 95% CI, 1.247 to 2.451), obesity (OR, 1.439; 95% CI, 1.133 to 1.828), and smoking (OR, 1.654; 95% CI, 1.287 to 2.127) were independent risk factors for overall CRN. Obesity and smoking as two modifiable factors increased the risk for high-risk CRN even more than for overall CRN (OR, 1.734; 95% CI, 1.168 to 2.575 and OR, 1.797; 95% CI, 1.172 to 2.753, respectively). Conclusions Obesity and smoking were modifiable risk factors for CRN in young adults. They increased the risk for high-risk CRN even more than for overall CRN. A colonoscopy might be beneficial for young individuals with these factors.

Seoul (SEOV) and Hantaan (HTNV) orthohantaviruses are significant zoonotic pathogens responsible for hemorrhagic fever with renal syndrome. Here, we investigated the molecular evolution of SEOV and HTNV through phylogenetic and bioinformatic analyses using complete genome sequences of their large (L), medium (M), and small (S) gene segments. Despite similar epizootic cycles and clinical symptoms, SEOV and HTNV exhibited distinct genetic and evolutionary dynamics. The phylogenetic trees of each segment consistently showed major genetic clades associated with the geographical distribution of both viruses. Remarkably, SEOV M and S segments exhibit higher evolutionary rates, rapidly increasing genetic diversity, and a more recent origin in contrast to HTNV. Reassortment events were infrequent, but both viruses appear to utilize the M gene segment in genetic exchanges. SEOV favors the L or M segment reassortment, while HTNV prefers the M or S segment exchange. Purifying selection dominates in all three gene segments of both viruses, yet SEOV experiences an elevated positive selection in its glycoprotein Gc ectodomain. Key amino acid differences, including a positive ‘lysine fence’ (through residues K77, K82, K231, K307, and K310) located at the tip of the Gn, alongside the physical stability around an RGD-like motif through M108-F334 interaction, may contribute to the unique antigenic properties of SEOV. With the increasing global dispersion and potential implications of SEOV for the global public health landscape, this study highlights the unique evolutionary dynamics and antigenic properties of SEOV and HTNV in informing vaccine design and public health preparedness.

Background/Aims: We examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication. Methods: A randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)- based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases. Results: In total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences. Conclusions: TPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier NCT03317223).

Background/Aims: This study evaluated the incidence of iatrogenic colonic perforation (ICP) in a high-volume center and analyzed the clinical outcomes and associated factors. Methods: As a retrospective study of the electronic medical records, the whole data of patients who underwent colonoscopy from June 2004 to May 2020 were reviewed. Results: During 16 years, 69,458 procedures were performed, of which 60,288 were diagnostic and 9,170 were therapeutic. ICP occurred in 0.027% (16/60,288) for diagnostic colonoscopies and in 0.076% (7/9,170) for therapeutic purposes (p=0.015; hazard ratio 2.878; 95% CI, 1.184-6.997). Fifty-two percent (12 cases) were managed with endoscopic clip closure, and 43.5% (10 cases) required surgery. The reasons for the procedure and the procedure timing appeared to affect the treatment decision. Perforations during therapeutic colonoscopy were treated with surgery more often than those for diagnostic purposes (66.7% [4/6] vs. 37.5% [6/16], p=0.221). Regarding the timing of the procedure, ICP that occurred in the afternoon session was more likely treated surgically (56.3% [9/16] vs. 0/5, p=0.027). Mortality occurred in two patients (2/23, 8.7%). Both were aged (mean age 84.0±1.4 vs. 65.7±10.5, p

Abstract Pandemics affect human lives severely and globally. Experience predicts that there will be a pandemic for sure although the time is unknown. When a viral epidemic breaks out, assessing its pandemic risk is an important part of the process that characterizes genomic property, viral pathogenicity, transmission in animal model, and so forth. In this review, we intend to figure out how a pandemic may occur by looking into the past influenza pandemic events. We discuss interpretations of the experimental evidences resulted from animal model studies and extend implications of viral pandemic potentials and ingredients to emerging viral epidemics. Focusing on the pandemic potential of viral infectious diseases, we suggest what should be assessed to prevent global catastrophes from influenza virus, Middle East respiratory syndrome coronavirus, dengue and Zika viruses.

Background/AimsA meta-analysis of randomized trials performed in healthy asymptomatic individuals suggested that overall mortality may increase after Helicobacter pylori eradication despite a significant decrease in the gastric cancer incidence and mortality rates. This retrospective population-based cohort study investigated if H. pylori treatment is associated with an increase in overall mortality in patients with hypertension.Methods : From the database of the Korean National Health Insurance Sample Cohort, we selected 198,487 patients treated for hypertension between 2002 and 2010. Those who received H. pylori treatment (H. pylori treatment cohort, 5,541 patients) were matched to those who did not (nontreatment cohort, 11,082 patients) at the ratio of 1 to 2. The primary outcome was the risk of overall mortality. The secondary outcomes were the risks of mortality due to cardiovascular disease, cerebrovascular disease, and cancer. The outcomes were evaluated from 6 months after H. pylori treatment to December 2013. A Cox proportional hazard model was used to estimate the hazard ratios (HRs).Results : During a median follow-up period of 4.8 years, death from any cause was reported in 4.1% of the patients in the H. pylori treatment cohort and 5.5% of the patients in the nontreatment cohort. The adjusted HR (aHR) for overall mortality in the H. pylori treatment cohort was 0.70 (95% confidence interval [CI], 0.60 to 0.82; p

Cross-species transmission of viral diseases alarms our global community for its potential of novel pandemic events. Of various viral pathogens noted recently, parvoviruses have posed public health threats not only to humans but to wild animals. To investigate the prevalence of parvoviruses in wild Manchurian chipmunks, here we detected genetic fragments of the nonstructural protein of parvovirus by polymerase chain reaction in wild Manchurian chipmunk specimens captured in the central and southern regions of South Korea and compared their sequence homology with references. Of a total of 348 specimens examined, chipmunk parvovirus (ChpPV)-specific gene fragments were detected with a 31.32 % rate (109 chipmunks of 348) in their kidney, liver, lung, and spleen samples, and the chipmunks captured in Gangwon Province exhibited the highest positive rate (45.37%), followed by Gyeongsang (35.29%), Gyeonggi (31.03%), Chungcheong (20.00%), and Jeolla (19.70%). When compared with the reference sequences registered in GenBank, a partial ChpPV sequence showed 97.70% identity to the previously reported Korean strain at the nucleic acid level. In the phylogenetic analysis, ChpPV exhibited closer relationship to primate parvoviruses, erythroviruses, and bovine parvovirus than to adeno-associated viruses. Despite limited sample size and genetic sequences examined in this study, our results underline the prevalence of ChpPV in Korea and emphasize the need of close surveillance of parvoviruses in wild animals.

Background/AimsThis nationwide, multicenter prospective randomized controlled trial aimed to compare the efficacy and safety of 10-day concomitant therapy (CT) and 10-day sequential therapy (ST) with 7-day clarithromycin-containing triple therapy (TT) as first-line treatment for Helicobacter pylori infection in the Korean population.Methods : Patients with H. pylori infection were assigned randomly to 7d-TT (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for 7 days), 10d-ST (lansoprazole 30 mg and amoxicillin 1 g twice daily for the first 5 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg twice daily for the remaining 5 days), or 10d-CT (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 10 days). The primary endpoint was eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses.Results : A total of 1,141 patients were included. The 10d-CT protocol achieved a markedly higher eradication rate than the 7d-TT protocol in both the ITT (81.2% vs 63.9%) and PP analyses (90.6% vs 71.4%). The eradication rate of the 10d-ST protocol was superior to that of the 7d-TT protocol (76.3% vs 63.9%, ITT analysis; 85.0% vs 71.4%, PP analysis). No significant differences in adherence or serious side effects were found among the three treatment arms.Conclusion : sThe 10d-CT and 10d-ST regimens were superior to the 7d-TT regimen as standard first-line treatment in Korea.

Background/Aims Irsogladine maleate, an enhancer of gastric mucosal protective factors, has demonstrated its efficacy for various gastric mucosal injuries. The aim of this study was to evaluate the efficacy and safety of irsogladine for prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin-induced peptic ulcer and gastritis. Methods In this multicenter, randomized, double-blind, exploratory clinical trial, 100 patients over 50 years of age who needed continuous NSAIDs or aspirin for more than 8 weeks were randomly assigned to either test group (irsogladine maleate 2 mg, twice daily, 39 patients for full analysis) or placebo group (37 patients for full analysis). Primary outcomes were incidence of peptic ulcer and ratio of modified Lanza score (MLS) 2 to 4. Secondary outcome was the number of acute erosions confirmed by endoscopy at 8 weeks. Adverse effects were also compared. Results There were no significant differences in gastric protective effects between test and placebo groups. However, two cases of peptic ulcer in the placebo group but none in the test group were observed. These two cases of peptic ulcer were Helicobacter pylori-negative. In addition, H. pylori-negative group showed significant changes in MLS score (p = 0.0247) and edema score (p = 0.0154) after the treatment compared to those before treatment in the test group. There was no significant difference in adverse events between the two groups. Conclusions The efficacy of irsogladine maleate was found in H. pylori-negative group, suggesting its potential as a protective agent against NSAIDs or aspirin-induced peptic ulcer and gastritis.

Background/Aims Atrophic gastritis and intestinal metaplasia are sequential consequences of chronic Helicobacter pylori (H. pylori) infection. These conditions are well known to increase the risk of gastric adenocarcinoma development. Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is also a malignant consequence of H. pylori infection, but the relationship between gastric MALT lymphoma and atrophic gastritis-intestinal metaplasia has not been a focus of interest. We investigated the clinical characteristics of atrophic gastritis and intestinal metaplasia in patients with gastric MALT lymphoma. Materials and Methods A study was conducted by reviewing the electronic medical records of patients diagnosed as having gastric MALT lymphoma at an academic institute, the Yeouido St. Mary's Hospital, Seoul, Korea, between January 2001 and December 2018. Results Fifty-eight subjects were enrolled consecutively during the study period and analyzed retrospectively. The patients’ mean age was 56.9 years old. The male-to-female ratio was 1.15 (31/27). On histological examination, background atrophic gastritis and intestinal metaplasia were detected in 26.8% (15/58) of cases. Serum pepsinogen I, II and gastrin levels, as serological markers of atrophy, were evaluated in 28 subjects. Three (5.2%) of the 28 cases were compatible with serological atrophic gastritis (pepsinogen I/II ratio of

Gastrointestinal stromal tumor (GIST) is a mesenchymal tumor derived from Cajal cells originating from the myotonic plexus. The expression of tyrosine kinase (KIT) membrane receptors that are active on KIT is inhibited by the KIT inhibitor imatinib mesylate. GISTs are resistant to conventional chemotherapy, and radiation therapy is not significantly beneficial for GISTs. With the development of imatinib mesylate, approximately 81.6% of patients with advanced and metastatic GIST exhibit an effect above the stabilization response, thereby increasing the survival time. However, imatinib mesylate alone is unlikely to cure metastatic GISTs. Even with a partial or stable response, imatinib mesylate may be used for a longer time period. However, resection of grossly visible lesions should be considered for patients with a stable response during surgical treatment. In this study, we present a case of GIST with liver metastasis after imatinib mesylate treatment, which was followed up without recurrence after partial resection.

Of various rodent-borne hantaviruses, Seoul orthohantavirus (SEOV) causes haemorrhagic fever with renal syndrome (HFRS), as does Hantaan orthohantavirus (HTNV). Given global-scale of cases of human infection with SEOV, it is of great clinical importance to distinguish SEOV from other HFRS-causing hantaviruses. In May 2019, a middle-aged patient who had lived in a suburban area of Chungcheong Province, Republic of Korea and enjoyed outdoor activities was transferred to Asan Medical Center in Seoul, Republic of Korea with HFRS; his symptoms included high fever and generalized myalgia. The rapid diagnostic test performed immediately after his transfer detected HTNV-specific antibodies, and the patient was treated accordingly. However, two consecutive IFAs performed at ten-day intervals showed no HTNV-specific immunoglobulin (Ig) G. During continuous supportive care, next-generation sequencing successfully identified viral genomic sequences in the patient's serum, which were SEOV and not HTNV. Phylogenetic analysis grouped the L, M, and S genes of this SEOV strain together with those of rat- or human-isolated Korean strains reported previously. Given global outbreaks and public health threats of zoonotic hantaviruses, a causative pathogen of hantavirus HFRS should be identified correctly at the time of diagnosis and by point-of-care testing.

Zoonotic avian influenza viruses pose severe health threats to humans. Of several viral subtypes reported, the low pathogenic avian influenza H7N9 virus has since February 2013 caused more than 1,500 cases of human infection with an almost 40% case-fatality rate. Vaccination of poultry appears to reduce human infections. However, the emergence of highly pathogenic strains has increased concerns about H7N9 pandemics. To develop an efficacious H7N9 human vaccine, we designed vaccine viruses by changing the patterns of N-linked glycosylation (NLG) on the viral hemagglutinin (HA) protein based on evolutionary patterns of H7 HA NLG changes. Notably, a virus in which 2 NLG modifications were added to HA showed higher growth rates in cell culture and elicited more cross-reactive antibodies than did other vaccine viruses with no change in the viral antigenicity. Developed into an inactivated vaccine formulation, the vaccine virus with 2 HA NLG additions exhibited much better protective efficacy against lethal viral challenge in mice than did a vaccine candidate with wild-type (WT) HA by reducing viral replication in the lungs. In a ferret model, the 2 NLG-added vaccine viruses also induced hemagglutination-inhibiting antibodies and significantly suppressed viral replication in the upper and lower respiratory tracts compared with the WT HA vaccines. In a mode of action study, the HA NLG modification appeared to increase HA protein contents incorporated into viral particles, which would be successfully translated to improve vaccine efficacy. These results suggest the strong potential of HA NLG modifications in designing avian influenza vaccines.

Roll-to-roll nanoimprint lithography (RTR-NIL) is a low-cost and continuous fabrication process for large-area functional films. However, the partial ultraviolet (UV) resin filling obstructs the ongoing production process. This study incorporates UV resin filling process into the nanopillars and nanopores by using RTR-NIL. A multiphase numerical model with a sliding mesh method is proposed in this study to show the actual phenomena of imprint mold rotation and feeding of UV resin on the polyethylene terephthalate (PET) substrate. The implementation of UV resin filling under environmental conditions was performed by utilizing the open-channel (OC) boundary conditions. The numerical model was solved by using the explicit volume of fluid (VOF) scheme to compute the filling on each node of the computational domain. The effects of different processing parameters were investigated through the proposed numerical model such as imprinting speed (IS), contact angles (CAs), viscosity, initial thickness of the PET, and supporting roll diameter. A good agreement was found between numerical simulations and experimental results. The proposed numerical model gives better insights of the filling process for the mass production of functional surfaces with nanopillars and nanopores patterns for different applications on an industrial scale.

Lymphangioma of the esophagus is a rare submucosal benign tumor. A 49-year-old man was referred because of a foreign body sensation in the esophagus. In endoscopy, a 10.0×1.0-cm longitudinal, translucent, whitish yellow mass covered with normal esophageal mucosa was found in the lower esophagus. Endoscopic ultrasonography revealed a heterogeneous, mainly hypoechoic, well-circum-scribed lesion located in the third layer. Incisional biopsy was performed, and histologic findings showed multiple dilated lymphatic vessels, consistent with lymphangioma. After 3 months of proton pump inhibitor treatment, the symptom was relieved and the patient is currently asymptomatic and under surveillance.

Background/Aims Rebleeding is associated with mortality in patients with peptic ulcer bleeding (PUB), and risk stratification is important for the management of these patients. The purpose of our study was to examine the risk factors associated with rebleeding in patients with PUB. Methods : The Korean Peptic Ulcer Bleeding registry is a large prospectively collected database of patients with PUB who were hospitalized between 2014 and 2015 at 28 medical centers in Korea. We examined the basic characteristics and clinical outcomes of patients in this registry. Univariate and multivariate analyses were performed to identify the factors associated with rebleeding. Results : In total, 904 patients with PUB were registered, and 897 patients were analyzed. Rebleeding occurred in 7.1% of the patients (64), and the 30-day mortality was 1.0% (nine patients). According to the multivariate analysis, the risk factors for rebleeding were the presence of co-morbidities, use of multiple drugs, albumin levels, and hematemesis/hematochezia as initial presentations. Conclusion : s The presence of co-morbidities, use of multiple drugs, albumin levels, and initial presentations with hematemesis/hematochezia can be indicators of rebleeding in patients with PUB. The wide use of proton pump inhibitors and prompt endoscopic interventions may explain the low incidence of rebleeding and low mortality rates in Korea.

Abstract Background Most international guidelines recommend triple-therapy regimens consisting of a proton pump inhibitor, clarithromycin, and amoxicillin/metronidazole for at least 7 days for the eradication of Helicobacter pylori. However, the efficacy of 7-day clarithromycin-based standard triple therapy for H. pylori infection is currently unacceptable in Korea. In this study, we will compare the efficacy and safety of 7-day standard triple therapy, 10-day sequential therapy, and 10-day concomitant therapy for the first-line treatment of H. pylori infection in Korea. Methods/design In this multicenter, investigator-blinded, randomized trial we are recruiting adult patients with H. pylori infection from 15 hospitals in Korea to determine whether sequential or concomitant treatment is superior to standard triple therapy. Patients are randomly assigned to receive either standard triple therapy (lansoprazole, amoxicillin, and clarithromycin) for 7 days, or sequential treatment (lansoprazole and amoxicillin for the first 5 days, followed by lansoprazole, clarithromycin, and metronidazole for another 5 days) for 10 days, or concomitant therapy (lansoprazole, amoxicillin, clarithromycin, and metronidazole) for 10 days. The primary outcome is the rate of H. pylori eradication in the intention-to-treat population. Discussion The results of this study will be crucial for determining the optimal regimen for the primary treatment of H. pylori infection in Korea. This study will produce vital evidence that will lead to revisions to guidelines concerning first-line treatment regimens for H. pylori infection. Trial registration Clinical Research Information Service (CRIS), Republic of Korea, KCT0001980. Registered on 25 July 2016.

Abstract It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry. We identified this molecular alteration after the adaptation of a 2009 pandemic H1N1 virus (pH1N1) in BALB/c mice. The mouse-adapted pH1N1 lost its eight consecutive amino acids including one potential N-linked glycosite from the NA stalk region. To explore the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes, we generated NA stalk mutant viruses on the pH1N1 backbone by reverse genetics. Intriguingly, either NA stalk truncation or deglycosylation changed pH1N1 into a lethal virus to mice by resulting in extensive pathologic transformation in the mouse lungs and systemic infection affecting beyond the respiratory organs in mice. The increased pathogenicity of these NA stalk mutants was also reproduced in ferrets. In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model. Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.

Zoonotic transmission of orthohantaviruses from rodent reservoirs to humans has been the cause of severe fatalities. Human infections are reported worldwide, but vaccines have been approved only in China and Korea. Orthohantavirus vaccine development has been pursued with no sense of urgency due to the relative paucity of cases in countries outside China and Korea. However, the orthohantaviruses continuously evolve in hosts and thus the current vaccine may not work as well against some variants. Therefore, a more effective vaccine should be prepared against the orthohantaviruses. In this review, we discuss the issues caused by the orthohantavirus vaccine. Given the pros and cons of the orthohantavirus vaccine, we suggest strategies for the development of better vaccines in terms of pandemic preparedness.

Background/AimsThe purpose of this study is to investigate the recurrence rate of peptic ulcer disease (PUD) over a long follow-up period with PUD patients without Helicobacter pylori.Methods : We retrospectively reviewed patients diagnosed with PUD on endoscopy and divided them into two groups: a H. pylori-negative group (HP-negative group), and a group of patients with untreated H. pylori (HP noneradicated group). We compared the recurrence rates of PUD in these two groups and analyzed the factors that affected ulcer recurrence.Results : Total of nine hospitals in Korea participated, and a total of 1,761 patients were retrospectively reviewed. The HP-negative group included 553 patients, and the HP noneradicated group included 372 patients. The 5-year cumulative probabilities of PUD recurrence were 36.4% in the HP-negative group and 43.8% in the HP noneradicated group (p=0.113). The factors that were found to affect recurrence in the HP-negative group were elder, male, and comorbid chronic kidney disease.Conclusion : sThe 5-year cumulative probability of PUD recurrence without H. pylori infection after a long-term follow-up was 36.4% and the factors that affected recurrence were elder, male, and comorbid chronic kidney disease.

Background/AimsEradication of Helicobacter pylori infection with standard triple therapy (TT) has declined primarily because of increased antibiotic resistance. Sequential therapy (ST) has been suggested as an alternative to TT for the first-line treatment of H. pylori. The purpose of this study was to compare the efficacy of ST with TT.Methods : This was a multicenter, randomized open-label trial performed at nine centers in Korea. Patients with H. pylori infection were randomly assigned to receive either 7 day TT or 10 day ST. Eradication rates, drug compliance, and adverse events were compared among the two regimens.Results : A total of 601 patients were enrolled between March 2011 and September 2014. The intention-to-treat eradication rates were 70.8% for TT and 82.4% for ST (p=0.001). The corresponding per protocol eradication rates were 76.9% and 88.8% for TT and ST, respectively (p=0.000). There were no statistically significant differences between the two regimens with respect to drug compliance and adverse events.Conclusion : sST achieved better eradication rates than TT as a first-line therapy for H. pylori eradication in Korea.

Pneumatosis cystoides intestinalis (PCI) is a rare condition characterized by multiple gas-filled cysts of varying size in the wall of gastrointestinal tract. PCI may idiopathic or secondary to various disorders. The etiology and pathogenesis of PCI are unclear. Treatment is usually conservative, and includes oxygen and antibiotics therapy. Surgery is reserved for cases of suspected inconvertible intestinal obstruction or perforation. Eleven patients who were diagnosed with PI between 2005 and 2015 were reviewed. We report three cases of PCI and describe causes and complications. The most important point in the treatment of PCI is to determine whether the patient needs surgery. Conservative care should be considered first if the patient is stable. If any complication is observed, such as ischemia in the intestine, surgery is needed. It is important to choose the best treatment based on prognostic factors and CT findings. (Korean J Gastroenterol 2016;67:262-266)

Seasonal influenza is caused by two influenza A subtype (H1N1 and H3N2) and two influenza B lineage (Victoria and Yamagata) viruses. Of these antigenically distinct viruses, the H3N2 virus was consistently detected in substantial proportions in Korea during the 2010/11-2013/14 seasons when compared to the other viruses and appeared responsible for the influenza-like illness rate peak during the first half of the 2011/12 season. To further scrutinize possible causes for this, we investigated the evolutionary and serological relationships between the vaccine and Korean H3N2 strains during the 2011/12 season for the main antigenic determinants of influenza viruses, the hemagglutinin (HA) and neuraminidase (NA) genes. In the 2011/12 season, when the number of H3N2 cases peaked, the majority of the Korean strains did not belong to the HA clade of A/Perth/16/2009 vaccine, and no Korean strains were of this lineage in the NA segment. In a serological assay, post-vaccinated human sera exhibited much reduced hemagglutination inhibition antibody titers against the non-vaccine clade Korean H3N2 strains. Moreover, Korean strains harbored several amino acid differences in the HA antigenic sites and in the NA with respect to vaccine lineages during this season. Of these, the HA antigenic site C residues 45 and 261 and the NA residue 81 appeared to be the signatures of positive selection. In subsequent seasons, when H3N2 cases were lower, the HA and NA genes of vaccine and Korean strains were more phylogenetically related to each other. Combined, our results provide indirect support for using phylogenetic clustering patterns of the HA and possibly also the NA genes in the selection of vaccine viruses and the assessment of vaccine effectiveness.

Human metapneumovirus (HMPV) has been described as an important etiologic agent of upper and lower respiratory tract infections, especially in young children and the elderly. Most of school-aged children might be introduced to HMPVs, and exacerbation with other viral or bacterial super-infection is common. However, our understanding of the molecular evolution of HMPVs remains limited. To address the comprehensive evolutionary dynamics of HMPVs, we report a genome-wide analysis of the eight genes (N, P, M, F, M2, SH, G, and L) using 103 complete genome sequences. Phylogenetic reconstruction revealed that the eight genes from one HMPV strain grouped into the same genetic group among the five distinct lineages (A1, A2a, A2b, B1, and B2). A few exceptions of phylogenetic incongruence might suggest past recombination events, and we detected possible recombination breakpoints in the F, SH, and G coding regions. The five genetic lineages of HMPVs shared quite remote common ancestors ranging more than 220 to 470 years of age with the most recent origins for the A2b sublineage. Purifying selection was common, but most protein genes except the F and M2-2 coding regions also appeared to experience episodic diversifying selection. Taken together, these suggest that the five lineages of HMPVs maintain their individual evolutionary dynamics and that recombination and selection forces might work on shaping the genetic diversity of HMPVs.

Background. The decline of Helicobacter pylori (H. pylori) eradication rates with standard triple therapy resulted in a search for novel therapies for first-line therapy of H. pylori infection. Aim. The aim of the study is to compare the efficacy of concomitant therapy with sequential therapy as the first-line therapy of H. pylori eradication. Methods. We reviewed medical records of patients who were confirmed to have H. pylori infection and received eradication treatment from September 2012 to March 2015. The concomitant group was treated with rabeprazole, amoxicillin, clarithromycin, and metronidazole for 7 days. The sequential group was treated with rabeprazole and amoxicillin for 5 days and then rabeprazole, clarithromycin, and metronidazole for an additional 5 days. Six weeks after the treatment period, patients in both groups underwent 13C-Urea breath test (UBT) to confirm H. pylori eradication. Results. The eradication rate was 90.3% in the concomitant group and 85.5% in the sequential group. However, the eradication rates between the two groups showed no statistical difference (P=0.343). Conclusion. No statistical difference was found in eradication rates between the two groups. However, in areas where antibiotic resistance is high, concomitant therapy may be more effective than sequential therapy for H. pylori eradication.

Correction In the original publication [1] was an error in the grant number in the funding section. The correct version can be found in this Erratum.

Objectives. Sessile nonampullary duodenal tumors (SNADTs) are relatively rare and endoscopic resection of these lesions is considered more challenging than in other parts of the gastrointestinal tract. The aim of this study was to evaluate the feasibility of endoscopic resection for SNADT. Methods. Medical records including endoscopic resection for SNADT from July 2002 to July 2013 from 5 centers affiliated to The Catholic University of Korea were reviewed retrospectively. Demographic features and clinical outcomes such as complete resection and complications were analyzed. Results. A total of 56 lesions from 54 patients were enrolled in this study. Forty-five lesions were resected by endoscopic mucosal resection (EMR), 6 lesions by endoscopic submucosal dissection (ESD), and 5 lesions by simple polypectomy. Histologic examination after endoscopic resection revealed adenocarcinoma in 2, low grade adenoma in 25, high grade adenoma in 11, and carcinoid tumor in 18 lesions. En bloc resection rates and histological complete resection rates were 78.6% (44/56) and 80.0% (28/35), respectively. Bleeding which required additional endoscopic intervention occurred in 1.8% (1/56) and perforation in 7.1% (4/56). There was no procedure-related mortality. Conclusions. Endoscopic resection techniques including ESD might be safe and effective modalities for the management of SNADT.

Influenza A virus (IAV) can infect avian and mammalian species, including humans. The genome nature of IAVs may contribute to viral adaptation in different animal hosts, resulting in gene reassortment and the reproduction of variants with optimal fitness. As seen again in the 2009 swine-origin influenza A H1N1 pandemic, pigs are known to be susceptible to swine, avian, and human IAVs and can serve as a 'mixing vessel' for the generation of novel IAV variants. To this end, the emergence of swine influenza viruses must be kept under close surveillance. Herein, we report the isolation and phylogenetic study of a swine IAV, A/swine/Korea/PL01/2012 (swPL01, H3N2 subtype). After screening nasopharyngeal samples from pigs in the Gyeongsangnam-do region of Korea from December 2011 to May 2012, we isolated the swPL01 virus and sequenced its all of 8 genome segments (polymerase basic 2, PB2; polymerase basic 1, PB1; polymerase acidic, PA; hemagglutinin, HA; nucleocapsid protein, NP; neuraminidase, NA; matrix protein, M; and nonstructural protein, NS). The phylogenetic study, analyzed with reference strains registered in the National Center for Biotechnology Information (NCBI) database, indicated that the swPL01 virus was similar to the North American triple-reassortant swine strains and that the HA gene of the swPL01 virus was categorized into swine H3 cluster IV. The swPL01 virus had the M gene of the triple-reassortant swine H3N2 viruses, whereas that of other contemporary strains in Korea was transferred from the 2009 pandemic H1N1 virus. These data suggest the possibility that various swine H3N2 viruses may co-circulate in Korea, which underlines the importance of a sustained surveillance system against swine IAVs.

Proanthocyanidin (grape seed proanthocyanidin extracts, GSPEs) is an antioxidant and scavenges free radicals. Excessive oxidative stress and free radical production are major components in the pathogenesis of NSAID-induced small intestinal injury. We investigated the effect of GSPEs on indomethacin-induced intestinal mucosal injury in the rat. Rats were allocated into four groups: the null control group, the indomethacin control group, the low-dose GSPEs group, and the high-dose GSPEs group. GSPEs were administered for 4 days. Then indomethacin and GSPEs were coadministered for the following 2 days by oral route. The dose of indomethacin was 200 mg/Kg. The doses of GSPEs were 100 mg/Kg for low-dose group and 300 mg/Kg for high-dose group. Luminal bleeding was solely observed in one of 5 rats from indomethacin control group. The number of ulcer count was reduced to 0.1 ± 0.3 per rat in GSPEs treated group compared to 1.4 ± 0.5 per rat in indomethacin control group. Submucosal inflammatory cell infiltration was also reduced to 50% in GSPEs treated group. The tissue level of prostaglandin E2 was not affected by GSPEs treatment. GSPEs attenuated the indomethacin-induced small intestinal injury irrespective of the tissue PGE2 depletion and glutathione consumption.

Antiviral drugs are being used for therapeutic purposes against influenza illness in humans. However, antiviral-resistant variants often nullify the effectiveness of antivirals. Combined medications, as seen in the treatment of cancers and other infectious diseases, have been suggested as an option for the control of antiviral-resistant influenza viruses. Here, we evaluated the therapeutic value of combination therapy against oseltamivir-resistant 2009 pandemic influenza H1N1 virus infection in DBA/2 mice. Mice were treated for five days with favipiravir and peramivir starting 4 hours after lethal challenge. Compared with either monotherapy, combination therapy saved more mice from viral lethality and resulted in increased antiviral efficacy in the lungs of infected mice. Furthermore, the synergism between the two antivirals, which was consistent with the survival outcomes of combination therapy, indicated that favipiravir could serve as a critical agent of combination therapy for the control of oseltamivir-resistant strains. Our results provide new insight into the feasibility of favipiravir in combination therapy against oseltamivir-resistant influenza virus infection.