The combined use of anti-peptic agents is associated with an increased risk of osteoporotic fracture: a nationwide case-control study

Background/Aims@#Long-term use of acid suppressants such as proton pump inhibitors (PPIs) and histamine 2 receptor antagonist (H2RA) has been associated with the risk of osteoporotic fracture. Acid suppressants and muco-protective agents (MPAs) are often used together as anti-ulcer agents. We evaluated the association between the risk of osteoporotic fracture and the combined use of these anti-peptic agents. @*Methods@#A population-based case-control study was conducted by analyzing the Korean National Health Insurance Data from 2014 to 2020. Patients who had been prescribed anti-peptic agents, such as PPI, H2RA, or MPA, were included. Considering the incidence of osteoporotic fractures, the case group (n = 14,704) and control group (n = 58,816) were classified by 1:4 matching based on age and sex. @*Results@#The use of all types of anti-peptic agents was associated with an increased risk of osteoporotic fractures (PPI: hazard osteoratio [HR], 1.31; H2RA: HR, 1.44; and MPA: HR, 1.33; all p < 0.001). Compared to PPI alone, the combined use of “PPI and H2RA” (HR, 1.58; p = 0.010) as well as “PPI, H2RA, and MPA” (HR, 1.71; p = 0.001) was associated with an increased risk of osteoporotic fracture. However, compared with PPI alone, “MPA and PPI or H2RA” was not associated with an increased risk of osteoporotic fracture. @*Conclusions@#This study found that the combined use of “PPI and H2RA” was associated with a higher risk of osteoporotic fractures. In cases where deemed necessary, the physicians may initially consider prescribing the combination use of MPA.

Reduced risk of gastrointestinal bleeding associated with eupatilin in aspirin plus acid suppressant users: nationwide population-based study

Background/Aims@#Mucoprotective agents, such as eupatilin, are often prescribed to prevent gastrointestinal (GI) bleeding in addition to an acid suppressant despite the absence of a large-scale study. We evaluated the additional effect of eupatilin on the prevention of GI bleeding in both the upper and lower GI tract in concomitant aspirin and acid suppressant users using the nationwide database of national claims data from the Korean National Health Insurance Service (NHIS). @*Methods@#An aspirin cohort was constructed using the NHIS claims data from 2013 to 2020. Patients who manifested with hematemesis, melena, or hematochezia were considered to have GI bleeding. A Cox proportional hazards regression model was used to determine the risk factors for GI bleeding associated with the concomitant use of GI drugs and other covariates among aspirin users. @*Results@#Overall, a total of 432,208 aspirin users were included. The concurrent use of an acid suppressant and eupatilin (hazard ratio [HR] = 0.85, p = 0.016, vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding. Moreover, a more than 3-month duration (HR = 0.88, p = 0.030) of acid suppressant and eupatilin prescription (vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding. @*Conclusions@#Eupatilin administration for ≥ 3 months showed additional preventive effect on GI bleeding in concomitant aspirin and acid suppressant users. Thus, cotreatment with eupatilin with a duration of 3 months or longer is recommended for reducing GI bleeding among aspirin plus acid suppressant users.

Association between eupatilin and reduction in small bowel bleeding in aspirin users and aspirin plus acid suppressant users

Background/Aims@#Capsule endoscopy (CE) has shown that low-dose aspirin occasionally causes small bowel (SB) bleeding. We herein evaluated the protective effects of mucoprotective agents (MPAs) on SB bleeding in aspirin users using the nationwide database of claims data from the National Health Insurance Service (NHIS). @*Methods@#As CE is an insured procedure, we constructed an aspirin-SB cohort using NHIS claims data, with a maximum follow- up period of 24 months. Patients with anemia, melena, or hematochezia that occurred within 4 weeks before and after performing CE were suspected to have SB bleeding. A Cox proportional hazards regression model was used to determine the risk factors for SB bleeding. Subgroup analyses were conducted among patients who used acid suppressants, such as proton pump inhibitors (PPIs) and histamine-2 receptor antagonists. @*Results@#A total of 15,542 aspirin users were included. Anticoagulant use (hazard ratio [HR], 3.22), high Charlson comorbidity index score (≥ 2) (HR, 3.54), and PPI use (HR, 2.85) were significantly associated with SB bleeding, whereas eupatilin use (HR, 0.35) was a preventive factor. SB bleeding occurred more frequently in concurrent users of acid suppressants than in nonusers (1.3% vs. 0.5%). Subgroup analysis revealed that eupatilin significantly reduced the risk of SB bleeding in aspirin users with concurrent use of acid suppressants (HR, 0.23 vs. 2.55). @*Conclusions@#Eupatilin was associated with a reduced risk of SB bleeding in both aspirin users and those with concomitant use of acid suppressants. Eupatilin use should be considered for aspirin users, especially for those concomitantly taking acid suppressants.

A practical approach for small bowel bleeding

Gastrointestinal (GI) bleeding is one of the most common conditions among patients visiting emergency departments in Korea. GI bleeding is divided into upper and lower GI bleeding, according to the bleeding site. GI bleeding is also divided into overt and occult GI bleeding based on bleeding characteristics. In addition, obscure GI bleeding refers to recurrent or persistent GI bleeding from a source that cannot be identified after esophagogastroduodenoscopy or colonoscopy. The small intestine is the largest part of the alimentary tract. It extends from the pylorus to the cecum. The small intestine is difficult to access owing to its long length. Moreover, it is not fixed to the abdominal cavity. When hemorrhage occurs in the small intestine, the source cannot be found in many cases because of the characteristics of the small intestine. In practice, small-intestinal bleeding accounts for most of the obscure GI bleeding. Therefore, in this review, we introduce and describe systemic approaches and examination methods, including video capsule endoscopy and balloon enteroscopy, that can be performed in patients with suspected small bowel bleeding in clinical practice.

Cancer risk in patients with Peutz-Jeghers syndrome in Korea: a retrospective multi-center study

Background/Aims@#There have been little research on the cancer risks of patients with Peutz-Jeghers syndrome (PJS) in Korea. We aimed to investigate the clinical features of PJS patients and their cancer incidence rate. @*Methods@#Patients with PJS from nine medical centers were enrolled. In those patients diagnosed with cancer, data obtained included the date of cancer diagnosis, the tumor location, and the cancer stage. The cumulative risks of gastrointestinal cancers and extra-gastrointestinal cancers were calculated using the Kaplan-Meier method. @*Results@#A total of 96 PJS patients were included. The median age at diagnosis of PJS was 23.4 years. Cancer developed in 21 of the 96 patients (21.9%). The age of PJS diagnosis was widely distributed (0.9 to 72.4 years). The most common cancers were gastrointestinal cancer (n = 12) followed by breast cancer (n = 6). The cumulative lifetime cancer risk was calculated to be 62.1% at age 60. The cumulative lifetime gastrointestinal cancer risk was 47.1% at age 70. The cumulative lifetime extra- gastrointestinal cancer risk was 40.3% at age 60. @*Conclusions@#PJS onset may occur at any age and the risks of gastrointestinal and extra-gastrointestinal cancer are high. Thorough surveillance of PJS patients for malignancies is vital.

Propofol Alone versus Propofol in Combination with Midazolam for Sedative Endoscopy in Patients with Paradoxical Reactions to Midazolam

Background/Aims@#The efficacy of propofol in gastrointestinal endoscopy for patients with midazolam-induced paradoxical reactions remains unclarified. This study aimed to compare the efficacy and safety of propofol-based sedation in patients who previously experienced paradoxical reactions. @*Methods@#This was a prospective, single-blinded, randomized controlled pilot study. Participants with a history of paradoxical reactions to midazolam during a previous esophagogastroduodenoscopy were recruited and randomly assigned to group I (propofol monosedation) or group II (combination of propofol and midazolam). The primary endpoint was the occurrence of a paradoxical reaction. @*Results@#A total of 30 participants (mean age, 54.7±12.6 years; male, 19/30) were randomly assigned to group I (n=16) or group II (n=14). There were no paradoxical reactions in group I, but there were two in group II, without a significant difference (p=0.209). The mean dose of propofol was higher in group I than in group II (p=0.002). Meanwhile, the procedure and recovery times did not differ between groups. @*Conclusions@#Propofol-based sedation was safe and effective for patients who experienced paradoxical reactions to midazolam. However, caution is needed because few cases of paradoxical reaction again can happen in group II in which midazolam was readministered.

Osteoporosis Is Associated with an Increased Risk of Colorectal Adenoma and High-Risk Adenoma: A Retrospective, Multicenter, Cross-Sectional, Case-Control Study

Background/Aims@#The protective effects of vitamin D and calcium on colorectal neoplasms are known. Bone mineral density (BMD) may be a reliable biomarker that reflects the long-term anticancer effect of vitamin D and calcium. This study aimed to evaluate the association between BMD and colorectal adenomas including high-risk adenoma. @*Methods@#A multicenter, cross-sectional, case-control study was conducted among participants with average risk of colorectal cancer who underwent BMD and screening colonoscopy between 2015 and 2019. The main outcome was the detection of colorectal neoplasms. The variable under consideration was low BMD (osteopenia/osteoporosis). The logistic regression model included baseline demographics, components of metabolic syndrome, fatty liver disease status, and aspirin and multivitamin use. @*Results@#A total of 2,109 subjects were enrolled. The mean age was 52.1±10.8 years and 42.6% were male. The adenoma detection rate was 43%. Colorectal adenoma and high-risk adenoma were both more prevalent in subjects with low BMD than those with normal BMD (48.2% vs 38.8% and 12.1% vs 9.1%). In the univariate analysis, old age, male sex, smoking, metabolic components, fatty liver, and osteoporosis were significantly associated with the risk of adenoma and high-risk adenoma. In the multivariate analysis, osteoporosis was independently associated with risk of colorectal adenoma (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.11 to 2.46; p=0.014) and high-risk adenoma (OR, 1.94; 95% CI, 1.14 to 3.29; p=0.014). @*Conclusions@#Osteoporosis is an independent risk factor of colorectal adenoma and high-risk adenoma

Comparison of Oral Sulfate Solution and Polyethylene Glycol Plus Ascorbic Acid on the Efficacy of Bowel Preparation

Background/Aims@#The quality of bowel preparation is one of the quality indicators for colonoscopy. The aim of this study was to compare the efficacy of oral sulfate solution (OSS) and polyethylene glycol plus ascorbic acid (PEG-AA) for bowel preparation. @*Methods@#The study involved 167 patients who underwent diagnostic colonoscopies. Inadequate bowel preparation was defined as any score of ≤1 in each colon section based on the Boston Bowel Preparation Scale. Multivariate logistic regression was used to compare the efficacy of OSS and PEG-AA. Subgroup analyses were performed based on patient characteristics. @*Results@#Overall, 106 (63.5%) patients received OSS, and 61 (36.5%) patients received PEG-AA. The rate of inadequate bowel preparation was 12.3% in patients receiving OSS and 32.8% in patients receiving PEG-AA (p=0.001). OSS (odds ratio [OR] = 0.26; p=0.003) and morning examination (OR=0.11; p=0.038) were significantly associated with efficient bowel preparation. The efficacy of OSS compared with PEG-AA was only significant in patients ≥50 years of age vs. <50 years of age (OR=0.13; p=0.001 vs. OR=0.96; p=0.959) and female vs. male patients (OR=0.06; p=0.002 vs. OR=0.58; p=0.339). @*Conclusions@#OSS was significantly more efficient for bowel preparation than PEG-AA, especially in patients ≥50 years of age and female patients. Morning examination led to a good quality of bowel preparation, irrespective of the preparation regimen.

Pancreatic Hemangioma Suspected of Neuroendocrine Tumor / 대한소화기학회지

Adult pancreatic hemangioma is an extremely rare disease, with only 22 cases reported since 1939. Pancreatic hemangioma has no specific symptoms, diagnostic imaging, or laboratory findings, making it difficult to be clinically suspected and diagnosed. The majority are confirmed after surgery. In this report, a 61-year-old woman presented with melena and showed multiple small hyper- vascular lesions in the pancreas. A pancreatic neuroendocrine tumor was suspected, and the patient underwent a distal pancreatectomy. The pathology examination and immunohistochemical study revealed a pancreatic hemangioma.

Vegetarianism as a protective factor for asymptomatic colonic diverticulosis in Asians: a retrospective cross-sectional and case-control study

Background/Aims@#Dietary fiber intake is considered a protective factor for diverticular disease such as diverticulitis. However, evidence for an inverse connection between dietary fiber consumption and asymptomatic colonic diverticulosis is lacking. Specifically, few studies have investigated this subject in Asians with different presentations of diverticulosis. Therefore, we assessed the protective effects of a vegetarian diet for asymptomatic colonic diverticulosis in Buddhist monks who are obligatory vegetarians for spiritual reasons compared with the general population. @*Methods@#A retrospective, cross-sectional, case-control study was conducted in age- and sex-matched Buddhist monks and the general population who underwent colonoscopy for screening at a Korean health promotion center from August 2005 to June 2018. We compared the prevalence of asymptomatic diverticulosis between the 2 groups using a self-administered questionnaire. @*Results@#In this study, a total of 1,316 individuals were included (Buddhist monks of 658 and general population of 658) with a mean age of 52.6±9.5 years. The prevalence of asymptomatic diverticulosis in Buddhist monks was lower compared with the general population (6.7% [44/658] vs. 10.8% [71/658], P=0.008). Buddhist monks had a higher rate of high body mass index (BMI) and metabolic syndrome. By a multivariate regression analysis model, a nonvegetarian diet (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.21–2.72, P=0.004), old age (OR, 4.53; 95% CI, 1.36–15.12; P=0.014), male sex (OR, 1.91; 95% CI, 1.28–2.85; P=0.002), and a high BMI (OR, 1.50; 95% CI, 1.01–2.23; P=0.047) were independent predictors of asymptomatic diverticulosis. Moreover, a nonvegetarian diet was associated with both right-sided and left-sided diverticulosis. @*Conclusions@#A nonvegetarian diet may increase a risk of asymptomatic colonic diverticulosis in Asians.

Comparison of Fentanyl versus Meperidine in Combination with Midazolam for Sedative Colonoscopy in Korea

Background/Aims@#Combination of midazolam and opioids is used widely for endoscopic sedation. Compared with meperidine, fentanyl is reportedly associated with rapid recovery, turnover rate of endoscopy room, and quality of endoscopy. We compared fentanyl with meperidine when combined with midazolam for sedative colonoscopy. @*Methods@#A retrospective, cross-sectional, 1:2 matching study was conducted. Induction and recovery time were compared as the primary outcomes. Moreover, cecal intubation time, withdrawal time, total procedure time of colonoscopy, paradoxical reaction, adenoma detection rate, and adverse effect of midazolam or opioids were assessed as the secondary outcomes. @*Results@#A total of 129 subjects (43 fentanyl vs. 86 meperidine) were included in the analysis. The fentanyl group showed significantly more rapid induction time (4.5±2.7 min vs. 7.5±4.7 min, p<0.001), but longer recovery time (59.5±25.6 min vs. 50.3±10.9 min, p=0.030) than the meperidine group. In multivariate analysis, the induction time of the fentanyl group was 3.40 min faster (p<0.001), but the recovery time was 6.38 min longer (p=0.046) than that of the meperidine group. There was no difference in withdrawal time and adenoma detection rate between the two groups. @*Conclusions@#The fentanyl group had more rapid sedation induction time but longer recovery time than the meperidine group.

Surveillance colonoscopy in patients with sessile serrated adenoma

No abstract available.

Effect of Helicobacter pylori eradication on the regression of gastric polyps in National Cancer Screening Program

BACKGROUND/AIMS: Western guidelines recommend Helicobacter pylori eradication in H. pylori-associated gastric polyps; however, there is no standard guideline in Korea. The aim of this study is to assess the effect of H. pylori eradication on the regression of gastric hyperplastic polyps in National Cancer Screening Cohort, representative of general population. METHODS: Among participants in National Cancer Screening Program, subjects who had H. pylori positive gastric hyperplastic polyps less than 10 mm and underwent follow-up endoscopy and H. pylori testing were enrolled. The effect of H. pylori eradication on hyperplastic gastric polyps was estimated using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 183 H. pylori infected subjects with hyperplastic polyp at baseline underwent follow-up endoscopy and H. pylori test after mean of 2.2 years. Successful H. pylori eradication markedly induced the disappearance of hyperplastic polyps comparing to non-eradication group (83.7% vs. 34.1%, p = 0.001). Successful eradication increased the possibility of disappearance of hyperplastic polyps (adjusted OR, 5.56; 95% CI, 2.63 to 11.11). Polyp size was inversely related with the disappearance of hyperplastic polyps (adjusted OR, 59; 95% CI, 0.48 to 0.71). CONCLUSIONS: Eradication of H. pylori infection may induce disappearance of gastric hyperplastic polyps in National Cancer Screening Cohort.

Standard First-line Triple Therapy for Helicobacter pylori Infection: A Comparison of Eradication Rates Based on Timing of Administration of Proton Pump Inhibitors

BACKGROUND/AIMS: Recent Korean studies performed over the past few decades have shown diminishing efficacy and unacceptability of clarithromycin-based triple therapy as first-line eradication therapy for Helicobacter pylori infection, based on evidence of a declining eradication rate. Triple therapy continues to be used as first-line eradication therapy despite concerns regarding high clarithromycin resistance among Koreans. Patient compliance and acid suppression are important factors associated with the H. pylori eradication rate. We investigated whether regular administration of a proton pump inhibitor (PPI) 30 minutes before a meal can improve the eradication rate. MATERIALS AND METHODS: We retrospectively analyzed the data of 316 patients who were treated with first-line triple therapy (PPI, amoxicillin, and clarithromycin) for H. pylori infection between January 2012 and September 2017. Patients were divided into 2 groups based on the time of administration of the PPI (group A: before a meal, group B: after a meal). The urea breath test was performed 4~6 weeks after eradication of infection. RESULTS: Notably, 249 patients (78.8%, 249/316) showed successful eradication. The eradication rates in groups A and B were 87.5% (49/56 patients) and 76.9% (200/260 patients), respectively. We observed that regular administration of PPI before meals improved the eradication rate (P=0.079). CONCLUSIONS: We observed that although clarithromycin-based triple therapy was associated with an overall eradication rate <80%, regular PPI administration before meals improved the eradication rate. Regular PPI administration before meals and effective education to improve patient compliance could improve the eradication rate through maximal acid suppression.

Fitz-Hugh-Curtis syndrome is not uncommon / 대한내과학회지

Fitz-Hugh-Curtis (FHC) syndrome is hepatitis characterized by severe right upper abdominal pain associated with pelvic inflammatory disease (PID), mimicking the symptoms of acute abdomen, such as in acute cholecystitis. FHC syndrome is becoming more common with the increasing incidence of PID in Korea. We treated eight patients with FHC syndrome, who visited our hospital with right upper quadrant abdominal pain. We emphasize the importance of spiral computed tomography (CT) in the diagnosis of right upper quadrant abdominal pain in sexually active young women.

Clinical Characteristics and Risk Factors of Colon Polyps in Gyeongju and Pohang Area / 대한소화기학회지

BACKGROUND/AIMS: The purposes of this study were to investigate various environmental factors for colon polyps and to analyze locoregional clinical characteristics of colon polyps in Gyeongju and Pohang area. METHODS: From October 2005 to September 2006, patients who underwent colonoscopy were analyzed based on their ages, genders, body mass indices (BMI), dietary habits, smoking behaviors, accompaying diseases, and medications as risk factors for the occurrence of colon polyps. Then clinical manifestations, gross appearances and pathologic findings of polyps were investigated. RESULTS: Among 253 patients enrolled, a total of 296 colon polyps were found in 108 patients. The incidence of colon polyps in more than 50-year old patients was 3.2-fold greater compared to less than 50-year old patients. Smoking habits were also significantly associated with the occurence of colon polyps. Among adenomatous polyps, tubulovillous type and moderate to severe dysplasia were frequently observed as the size increased, yet the location of polyps was not significantly associated. CONCLUSIONS: Older age and smoking habit increase the risk of colon polyps. Rectal polyps have less chance to be adenomatous type. The larger the polyp grows, the more likely it to be tubulovillous and dysplastic.

A Case of an Intestinal Pseudo-obstruction in Post-encephalitis Mental Retardation / 대한소화기내시경학회지

A 44-year-old female patient, with developmental disabilities and mental retardation after central nervous system (CNS) infection during infancy, presented with a complaint of severe abdominal distension and weight loss for the past two months. The patient was diagnosed with an intestinal pseudo-obstruction, based on radiological findings and an endoscopic finding of marked gaseous distension of the stomach and the small bowel without stenosis and mechanical obstruction. The patient had delayed gastrointestinal mobility. We report a case of an intestinal pseudo-obstruction accompanied with mental retardation after CNS infection.

Clinical Associations between the Supplementary Examinations of the Terminal Ileal Mucosal Lesion and the Lesion of the Ileocecal Valve

BACKGROUND/AIMS: The diagnostic value of terminal ileum (TI) biopsies during colonoscopy remains controversial. This study assessed the clinical characteristics of terminal ileal lesions during colonoscopy to find the affecting factors for the specific investigations in addition to TI biopsies. METHODS: Thirty-seven patients (male to female ratio of 1.6, mean age 42.2+/-12.2 years, range 20-68 years) who had undergone colonoscopy with biopsies of TI at Dongguk University International Hospital from September 2005 to December 2007 were retrospectively studied. We analyzed the characteristics of patients, endoscopic and histopathologic findings, followed by multivariate analysis of those significant variables. RESULTS: Ulcerative lesions were most frequently found in 17 cases (45.9%) and multiple lesions were observed in eight cases (21.6%). Aphthoid shape was evident in 19 cases (51.4%). Eight cases (21.6%) were combined with ileocecal valve (ICV) lesion. On histopathologic examination, nonspecific inflammation was evident in 19 cases (51.4%). The diagnostic yield of TI biopsies was 5.4%. Presence of ICV lesion (p=0.004) and multiple lesions (p=0.027) were associated with clinically significant TI lesion. By multivariate analysis, only ICV lesion was statistically significant (Odds ratio 8.3: 95% confidence interval 1.3-54.1, p=0.026). CONCLUSIONS: Not all patients who undergo colonoscopy require intubation of TI. However, a careful examination of ICV could be useful to determine whether intubation of TI would be necessary or not.

The Importance of Gases in Portal Veins and Liver Parenchyme is Characterized by Liver Ultrasonography in Full-term Neonates with Necrotizing Enterocolitis

PURPOSE: Although early treatment of neonatal necrotizing enterocolitis (NEC) is very important, there exists no definite way of diagnosing NEC at an early stage. Previous reports argue that gases in portal veins and liver parenchyme are detected by liver ultrasonography (USG) even when no symptoms corresponding to NEC are provoked. This study demonstrates the importance of liver USG for early diagnosis of NEC. METHODS: Abdominal USG was performed on 1381 newborn infants who were admitted to the neonatal intensive care unit of Soonchunhyang University Cheonan Hospital between February 2003 and September 2005. Twelve infants were diagnosed with NEC by liver USG and their individual pathologies were compared. RESULTS: All of the patients described here were full-term and the most frequent symptom observed was watery diarrhea; four had no symptoms at all. Severe metabolic acidosis was seen in two patients, a rise of C-reactive protein (CRP) in five patients and rotavirus antigen positivity in five patients. One of the patients showed portal vein gas, pneumatosis intestinalis and ileus in a simple abdominal radiography and another patient showed ileus only. However, all of the other 10 patients presented with no abnormal symptoms, according to simple abdominal radiography. CONCLUSION: NEC should be considered in neonates with gases present in portal veins, intestinal walls and liver parenchyme, as detected by liver USG even when no symptoms corresponding to NEC are provoked.

A case of alkaptonuria: the first case in Korea / 소아과

Alkaptonuria is a rare metabolic disease in which homogentisic acid cannot be metabolized due to a lack of the enzyme homogentisic acid oxidase. The disease often manifests itself in childhood by darkening of the urine upon standing. The disease leads to such serious consequences as ochronosis of cartilage and connective tissues with arthritis. It is expected that treatment with ascorbic acid and a dietary restriction of protein may decrease the late and serious consequences by diminishing the serum concentration of the metabolite benzoquinone acetic acid. A thirteen month-old girl was recently diagnosed with alkaptonuria by urine organic acid analysis. She excreted pinkish urine on a diaper and as time went by the urine color changed to a light brown. In laboratory findings, urine examination and culture results were normal. But urine organic acid analysis detected abnormal findings a prominent and massive elevation of homogentisic acid. The other physical findings were normal. This is the first case diagnosed in Korea.