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Antibiotic resistance has emerged as a global threat to modern healthcare systems and has nullified many commonly used antibiotics. β-Lactam antibiotics are among the most successful and occupy approximately two-thirds of the prescription antibiotic market. They inhibit the synthesis of the peptidoglycan layer in the bacterial cell wall by mimicking the D-Ala-D-Ala in the pentapeptide crosslinking neighboring glycan chains. To date, various β-lactam antibiotics have been developed to increase the spectrum of activity and evade drug resistance. This review emphasizes the three-dimensional structural characteristics of β-lactam antibiotics regarding the overall scaffold, working mechanism, chemical diversity, and hydrolysis mechanism by β-lactamases. The structural insight into various β-lactams will provide an in-depth understanding of the antibacterial efficacy and susceptibility to drug resistance in multidrug-resistant bacteria and help to develop better β-lactam antibiotics and inhibitors.
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Background@#The most common type of carcinoma ex pleomorphic adenoma (CPA) is histologically equivalent to salivary duct carcinoma, which has an apocrine phenotype. Invasive CPA is often accompanied by non-invasive or in situ carcinoma, an observation that suggests the presence of precursor lesions. The aim of this study was to identify candidate precursor lesions of CPA within pleomorphic adenoma (PA). @*Methods@#Eleven resected cases of CPA with residual PA and 17 cases of PA with atypical changes were subjected to immunohistochemistry (IHC) for p53, human epidermal growth factor receptor 2 (HER2), androgen receptor (AR), pleomorphic adenoma gene 1, gross cystic disease fluid protein-15 (GCDFP-15), and anti-mitochondrial antibody. @*Results@#Invasive or in situ carcinoma cells in all CPAs were positive for AR, GCDFP-15, and HER2. Atypical foci in PAs corresponded to either apocrine or oncocytic changes on the basis of their reactivity to AR, GCDFP-15, and anti-mitochondrial antibody. Atypical cells in PAs surrounding CPAs had an apocrine phenotype without HER2 expression. @*Conclusions@#Our study identified frequent apocrine changes in residual PAs in CPA cases, suggesting a possible precursor role of apocrine changes. We recommend the use of HER2 IHC in atypical PAs, and that clinicians take HER2 positivity into serious consideration.
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Our objective was to investigate whether inflammatory microenvironment induced by Trichomonas vaginalis infection can stimulate proliferation of prostate cancer (PCa) cells in vitro and in vivo mouse experiments. The production of CXCL1 and CCL2 increased when cells of the mouse PCa cells (TRAMP-C2 cell line) were infected with live T. vaginalis. T. vaginalis-conditioned medium (TCM) prepared from co-culture of PCa cells and T. vaginalis increased PCa cells migration, proliferation and invasion. The cytokine receptors (CXCR2, CCR2, gp130) were expressed higher on the PCa cells treated with TCM. Pretreatment of PCa cells with antibodies to these cytokine receptors significantly reduced the proliferation, mobility and invasiveness of PCa cells, indicating that TCM has its effect through cytokine-cytokine receptor signaling. In C57BL/6 mice, the prostates injected with T. vaginalis mixed PCa cells were larger than those injected with PCa cells alone after 4 weeks. Expression of epithelial-mesenchymal transition markers and cyclin D1 in the prostate tissue injected with T. vaginalis mixed PCa cells increased than those of PCa cells alone. Collectively, it was suggested that inflammatory reactions by T. vaginalis-stimulated PCa cells increase the proliferation and invasion of PCa cells through cytokine-cytokine receptor signaling pathways.
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Purpose@#Single-incision cholecystectomy is a surgical method that offers comparable results to conventional laparoscopic cholecystectomy. However, a high risk of postoperative incisional hernia is an issue in single-incision cholecystectomy. This study evaluated the risk factors and incidences of incisional hernia after single-incision cholecystectomy and the advantage issue of using barbed suture material during wound closures. @*Methods@#A total of 1,111 patients underwent laparoscopic or robotic single-incision cholecystectomy between March 2014 and February 2020 at our institution at CHA Bundang Medical Center. During this period, there were 693 patients who underwent wound closure with monofilament suture material (Monosyn 2-0; B. Braun) and the other 418 patients used barbed suture material (Stratafix 2-0; Ethicon). @*Results@#The two patient groups were comparable in age, body mass index, and diagnosis. The total incidence of incisional hernia after single-incision cholecystectomy was 0.5% (five cases). All patients who developed incisional hernia were in the monofilament suture material group (0.7% vs. 0%, p = 0.021). The inf luence of predictive and possible risk factors on incisional hernia rate was analyzed. Among these factors, only old age was an independent predictive risk factor of incisional hernia. @*Conclusion@#Our study showed a low incidence of incisional hernia, all of which occurred in the monofilament suture material group. If technically appropriate, single-incision cholecystectomy does not appear to present a high incidence of hernia. Barbed suture material can be safely applied in wound closure showing comparable incisional hernia incidence to monofilament suture material.
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Background@#Cholecystitis is an important risk factor for gallbladder cancer, but the bile microbiome and its association with gallbladder disease has not been investigated fully.We aimed to analyze the bile microbiome in normal conditions, chronic cholecystitis, and gallbladder cancer, and to identify candidate bacteria that play an important role in gallbladder carcinogenesis. @*Methods@#We performed metagenome sequencing on bile samples of 10 healthy individuals, 10 patients with chronic cholecystitis, and 5 patients with gallbladder cancer, and compared the clinical, radiological, and pathological characteristics of the participants. @*Results@#No significant bacterial signal was identified in the normal bile. The predominant dysbiotic bacteria in both chronic cholecystitis and gallbladder cancer were those belonging to the Enterobacteriaceae family. Klebsiella increased significantly in the order of normal, chronic cholecystitis, and gallbladder cancer. Patients with chronic cholecystitis and dysbiotic microbiome patterns had larger gallstones and showed marked epithelial atypia, which are considered as precancerous conditions. @*Conclusion@#We investigated the bile microbiome in normal, chronic cholecystitis, and gallbladder cancer. We suggest possible roles of Enterobacteriaceae, including Klebsiella, in gallbladder carcinogenesis. Our findings reveal a possible link between a dysbiotic bile microbiome and the development of chronic calculous cholecystitis and gallbladder cancer.
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Purpose@#Single-incision cholecystectomy is a surgical method that offers comparable results to conventional laparoscopic cholecystectomy. However, a high risk of postoperative incisional hernia is an issue in single-incision cholecystectomy. This study evaluated the risk factors and incidences of incisional hernia after single-incision cholecystectomy and the advantage issue of using barbed suture material during wound closures. @*Methods@#A total of 1,111 patients underwent laparoscopic or robotic single-incision cholecystectomy between March 2014 and February 2020 at our institution at CHA Bundang Medical Center. During this period, there were 693 patients who underwent wound closure with monofilament suture material (Monosyn 2-0; B. Braun) and the other 418 patients used barbed suture material (Stratafix 2-0; Ethicon). @*Results@#The two patient groups were comparable in age, body mass index, and diagnosis. The total incidence of incisional hernia after single-incision cholecystectomy was 0.5% (five cases). All patients who developed incisional hernia were in the monofilament suture material group (0.7% vs. 0%, p = 0.021). The inf luence of predictive and possible risk factors on incisional hernia rate was analyzed. Among these factors, only old age was an independent predictive risk factor of incisional hernia. @*Conclusion@#Our study showed a low incidence of incisional hernia, all of which occurred in the monofilament suture material group. If technically appropriate, single-incision cholecystectomy does not appear to present a high incidence of hernia. Barbed suture material can be safely applied in wound closure showing comparable incisional hernia incidence to monofilament suture material.
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Background@#Cholecystitis is an important risk factor for gallbladder cancer, but the bile microbiome and its association with gallbladder disease has not been investigated fully.We aimed to analyze the bile microbiome in normal conditions, chronic cholecystitis, and gallbladder cancer, and to identify candidate bacteria that play an important role in gallbladder carcinogenesis. @*Methods@#We performed metagenome sequencing on bile samples of 10 healthy individuals, 10 patients with chronic cholecystitis, and 5 patients with gallbladder cancer, and compared the clinical, radiological, and pathological characteristics of the participants. @*Results@#No significant bacterial signal was identified in the normal bile. The predominant dysbiotic bacteria in both chronic cholecystitis and gallbladder cancer were those belonging to the Enterobacteriaceae family. Klebsiella increased significantly in the order of normal, chronic cholecystitis, and gallbladder cancer. Patients with chronic cholecystitis and dysbiotic microbiome patterns had larger gallstones and showed marked epithelial atypia, which are considered as precancerous conditions. @*Conclusion@#We investigated the bile microbiome in normal, chronic cholecystitis, and gallbladder cancer. We suggest possible roles of Enterobacteriaceae, including Klebsiella, in gallbladder carcinogenesis. Our findings reveal a possible link between a dysbiotic bile microbiome and the development of chronic calculous cholecystitis and gallbladder cancer.
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Purpose@#Gastric delta cells (D-cells), which are somatostatin-secreting cells, are the main paracrine inhibitor of acid secretion. The number of D-cells was studied in children presenting with upper gastrointestinal (UGI) disease. @*Methods@#We retrospectively investigated the number of D-cells in the gastric body and antrum through immunofluorescence examinations according to symptoms, endoscopic findings, and Helicobacter pylori infection in 75 children who visited Hanyang University Hospital Pediatrics. @*Results@#The mean patient age was 12.2±3.3 years. The male-to-female ratio was 1:1.4. The mean D-cell number per high-power field in the antrum and body was 20.5 and 12 in children with substernal pain, 18.3 and 10.3 in vomiting, 22.3 and 6 in diarrhea, and 9.3 and 6 in abdominal pain, respectively (p>0.05). According to endoscopic findings, the mean D-cell number in the antrum and body was 14.3 and 6 with gastritis, 14 and 9.3 with reflux esophagitis, 16.7 and 8.7 with duodeno-gastric reflux, 19.3 and 12.7 with gastric ulcer, 16 and 13.7 with duodenitis, and 12.3 and 4 with duodenal ulcer, respectively (p>0.05). The D-cell number in the gastric body was 2.7 and 8.7 in children with current H. pylori infection and non-infected children, respectively (p=0.01), while those in the antrum were 15.5 and 14, respectively, with no statistical significance. @*Conclusion@#The D-cell number was lower in the gastric body of children with current H. pylori infection. Further studies concerning peptide-secreting cells with a control group would provide information about the pathogenic pathways of UGI disorder.
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Background@#and Purpose: The myelin oligodendrocyte glycoprotein (MOG) antibody is detected at a high rate in childhood acquired demyelinating syndrome (ADS). This study aimed to determine the diagnostic value of the MOG antibody in ADS and the spectrum of MOGantibody-positive demyelinating diseases in children. @*Methods@#This study included 128 patients diagnosed with ADS (n=94) or unexplained encephalitis (n=34). The MOG antibody in serum was tested using an in-house live-cell-based immunofluorescence assay. @*Results@#The MOG antibody was detected in 48 patients (46 ADS patients and 2 encephalitis patients, comprising 23 males and 25 females). Acute disseminated encephalomyelitis (ADEM) (35.4%) was the most-common diagnosis, followed by the unclassified form (17.4%), isolated optic neuritis (ON) (15.2%), neuromyelitis optica spectrum disorder (13.0%), multiple sclerosis (MS) (10.8%), other clinically isolated syndromes [monophasic event except ADEM, isolated ON, or transverse myelitis (TM)] (8.7%), and unexplained encephalitis (4.3%). At the initial presentation, 35 out of the 46 patients with ADS had brain lesions detected in magnetic resonance imaging, and 54% of these 35 patients had encephalopathy. Nine of the 11 patients without brain lesions exhibited only ON. Thirty-nine percent of the patients experienced a multiphasic event during the mean follow-up period of 34.9 months (range 1.4–169.0 months). Encephalopathy at the initial presentation was frequently confirmed in the monophasic group (p= 0.011). @*Conclusions@#MOG antibodies were identified in all pediatric ADS phenotypes except for monophasic TM. Therefore, the MOG antibody test is recommended for all pediatric patients with ADS, especially before a diagnosis of MS and for patients without a clear diagnosis.
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Purpose@#Mesenchymal epithelial transition (MET) is a proto-oncogene that encodes a heterodimerictransmembrane receptor tyrosine kinase for the hepatocyte growth factor. Aberrant METsignaling has been described in several solid tumors—especially non-small cell lung cancer—and is associated with tumor progression and adverse prognosis. As MET is a potentialtherapeutic target, information regarding its prevalence and clinicopathological relevanceis crucial. @*Materials and Methods@#We investigated MET expression and gene amplification in 113 gallbladder cancers usingtissue microarray. Immunohistochemistry was used to evaluate MET overexpression, andsilver/fluorescence in situ hybridization (ISH) was used to assess gene copy number. @*Results@#MET overexpression was found in 37 cases of gallbladder carcinoma (39.8%), and geneamplification was present in 17 cases (18.3%). MET protein expression did not correlatewith MET amplification. MET amplification was significantly associated with aggressive clinicopathologicalfeatures, including high histological grade, advanced pT category, lymphnode metastasis, and advanced American Joint Committee on Cancer stage. There was nosignificant correlation between any clinicopathological factors and MET overexpression. Nodifference in survival was found with respect to MET overexpression and amplification status. @*Conclusion@#Our data suggested that MET might be a potential therapeutic target for targeted therapyin gallbladder cancer, because MET amplification was found in a subset of tumors associatedwith adverse prognostic factors. Detection of MET amplification by ISH might be a usefulpredictive biomarker test for anti-MET therapy.
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BACKGROUND@#We investigated the association between blood concentration of cadmium and smoking status including use of electronic cigarettes (E-cigars).@*METHODS@#We used data from the Korea National Health and Nutritional Survey 2013 and 2016. A total of 4,744 participants (2,162 men and 2,582 women) were included and were categorized into five groups (Non-smokers, E-cigar non-users in past-smokers, E-cigar users in past-smokers, E-cigar non-users in cigarette-smokers and E-cigar users in cigarette-smokers). Cadmium blood concentration was categorized into tertiles. All sampling and weight variables were stratified, and analysis to account for the complex sampling design was conducted.@*RESULTS@#In both genders, the geometric cadmium concentration was significantly different according to smoking status (both genders, analysis of variance P value < 0.001). In men, E-cigar users were significantly higher than the non-smokers (P value = past-smokers, 0.017; cigarette-smokers, < 0.001) when fully adjusted. Compared with non-smokers, fully-adjusted odds ratios (95% confidence intervals) for the highest cadmium tertiles of E-cigar non-users in cigarette-smokers and E-cigar users in cigarette-smokers were 6.56 (3.55–12.11) and 5.68 (1.96–16.50) in men and 2.74 (1.42–5.29) and 1.29 (0.10–17.44) in women.@*CONCLUSION@#Conventional cigarette smoking in men and women and E-cigar use in men are associated with higher risk of elevated blood cadmium level. Preventive management of cadmium exposure monitoring in conventional cigarette-smokers and E-cigar users may be needed.
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BACKGROUND@#We investigated the association between blood concentration of cadmium and smoking status including use of electronic cigarettes (E-cigars).@*METHODS@#We used data from the Korea National Health and Nutritional Survey 2013 and 2016. A total of 4,744 participants (2,162 men and 2,582 women) were included and were categorized into five groups (Non-smokers, E-cigar non-users in past-smokers, E-cigar users in past-smokers, E-cigar non-users in cigarette-smokers and E-cigar users in cigarette-smokers). Cadmium blood concentration was categorized into tertiles. All sampling and weight variables were stratified, and analysis to account for the complex sampling design was conducted.@*RESULTS@#In both genders, the geometric cadmium concentration was significantly different according to smoking status (both genders, analysis of variance P value < 0.001). In men, E-cigar users were significantly higher than the non-smokers (P value = past-smokers, 0.017; cigarette-smokers, < 0.001) when fully adjusted. Compared with non-smokers, fully-adjusted odds ratios (95% confidence intervals) for the highest cadmium tertiles of E-cigar non-users in cigarette-smokers and E-cigar users in cigarette-smokers were 6.56 (3.55–12.11) and 5.68 (1.96–16.50) in men and 2.74 (1.42–5.29) and 1.29 (0.10–17.44) in women.@*CONCLUSION@#Conventional cigarette smoking in men and women and E-cigar use in men are associated with higher risk of elevated blood cadmium level. Preventive management of cadmium exposure monitoring in conventional cigarette-smokers and E-cigar users may be needed.
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Female , Humans , Male , Cadmium , Electronic Nicotine Delivery Systems , Korea , Nutrition Surveys , Odds Ratio , Smoke , Smoking , Tobacco , Tobacco ProductsABSTRACT
PURPOSE: To investigate the relationship between thyroid abnormality and dry eye syndrome (DES) in a nationally representative Korean population. METHODS: A population-based prospective cross-sectional study was conducted, using the thyroid abnormality data set of the Korean National Health and Nutrition Examination Survey, 2010 – 2012. A total of 16,966 Korean participants with DES were enrolled in the study. RESULTS: The DES patients were predominantly women, non-smokers and non-drinkers, living in urban regions, with a low income and body mass index (BMI), and with a higher percentage of hypertension, hyperlipidemia, thyroid abnormalities, thyroid diseases, and thyroid cancers. After adjusting for all significant variables, thyroid abnormality (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.43–2.61), thyroid disease (OR, 1.85; 95% CI, 1.37–2.52), and thyroid cancer (OR, 2.45; 95% CI, 1.06–5.67) were significantly associated with DES. There was also a significant association between DES and thyroid abnormalities (OR, 2.02; 95% CI, 1.47–2.76), thyroid diseases (OR, 1.93; 95% CI, 1.41–2.65), and thyroid cancer (OR, 2.62; 95% CI, 1.06–6.62) in the female group, but there was no significant association in the male group. CONCLUSIONS: Thyroid abnormalities, thyroid diseases, and thyroid cancers were associated with DES in a nationally representative Korean population. Close evaluation of thyroid abnormalities is therefore needed when treating female patients.
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Female , Humans , Male , Body Mass Index , Cross-Sectional Studies , Dataset , Dry Eye Syndromes , Hyperlipidemias , Hypertension , Nutrition Surveys , Prospective Studies , Republic of Korea , Thyroid Diseases , Thyroid Gland , Thyroid NeoplasmsABSTRACT
PURPOSE: We report a case of Aeromonas keratitis presenting as radial keratoneuritis. CASE SUMMARY: A 33-year-old woman with a history of cleaning her contact lenses with tap water presented with decreased visual acuity for 1 day in the left eye. The patient showed diffuse corneal edema, stromal infiltration, and radial keratoneuritis, which were thought to be pathognomonic for Aeromonas keratitis. Based on the patient's clinical findings and past history, a diagnosis of Aeromonas keratitis was made and she was prescribed topical fortified cefazolin (50 mg/mL, 5%), tobramycin (3 mg/mL), and 0.02% chlorhexidine per hour. Culture results from the contact lens and contact lens solution confirmed infection by Aeromonas hydrophilia. Polymerase chain reaction results for Aeromonas were negative. After 8 days of treatment, the uncorrected visual acuity was 0.7/0.3 with improvement in her corneal findings. CONCLUSIONS: Radial keratoneuritis is not always pathognomic for Aeromonas keratitis and can be present in Aeromonas keratitis. Therefore, ophthalmologists should be cautious when interpreting this clinical sign.
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Adult , Female , Humans , Aeromonas , Cefazolin , Chlorhexidine , Contact Lens Solutions , Contact Lenses , Cornea , Corneal Edema , Diagnosis , Keratitis , Polymerase Chain Reaction , Tobramycin , Visual Acuity , WaterABSTRACT
PURPOSE: We report a case of utilizing a previous silicone band track in the reoperation of scleral encircling. CASE SUMMARY: An 8-year-old male presented with rhegmatogenous retinal detachment in the right eye. Five days after this diagnosis, he received scleral buckling surgery and cryopexy to seal the retinal tear. One month after surgery, a fundus examination showed subretinal fluid at the inferior site of the scleral buckle. He underwent scleral encircling surgery and a cryopexy procedure. The patient has had an uneventful postoperative course, and the retina has remained attached over a follow-up period of 9 months. However, exotropia and hypotropia developed in the right eye. Diagnosis of restrictive strabismus due to tissue adhesion around the silicone band was made. The encircling band was therefore removed and laser photocoagulation was performed 360° around the retina. Twenty-four hours after surgery, a fundus examination showed subretinal fluid. He received 360° scleral encircling surgery not using the 360° conjunctival peritomy. After confirming a previous encircling tract using #0-0 polydioxanone as a guide, #5-0 Nylon was tied to the end of the guide and inserted through the encircling tract with the end sutured with the silicone band. The silicone band was inserted into the encircling tract by pulling the #5-0 Nylon as a guide. Ophthalmoscopy revealed an attached retina with indentation of the scleral buckle at 360°. CONCLUSIONS: For reoperation in patients who previously underwent scleral encircling surgery, using the previous scleral encircling tract may be effective in cases with conjunctival and tissue adhesion.
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Child , Humans , Male , Diagnosis , Exotropia , Follow-Up Studies , Light Coagulation , Nylons , Ophthalmoscopy , Polydioxanone , Reoperation , Retina , Retinal Detachment , Retinal Perforations , Retinaldehyde , Scleral Buckling , Silicon , Silicones , Strabismus , Subretinal Fluid , Tissue AdhesionsABSTRACT
BACKGROUND: Lung cancer is the most common cause of cancer-related death, and adenocarcinoma is the most common histologic subtype. MicroRNA is a small non-coding RNA that inhibits multiple target gene expression at the post-transcriptional level and is commonly dysregulated in malignant tumors. The purpose of this study was to analyze the expression of microRNA-374a (miR-374a) in lung adenocarcinoma and correlate its expression with various clinicopathological characteristics.METHODS: The expression level of miR-374a was measured in 111 formalin-fixed paraffin-embedded lung adenocarcinoma tissues using reverse transcription-quantitative polymerase chain reaction assays. The correlation between miR-374a expression and clinicopathological parameters, including clinical outcome, was further analyzed.RESULTS: High miR-374 expression was correlated with advanced pT category (chi-square test, p=.004) and pleural invasion (chi-square test, p=.034). Survival analysis revealed that patients with high miR-374a expression had significantly shorter disease-free survival relative to those with low miR-374a expression (log-rank test, p=.032).CONCLUSIONS: miR-374a expression may serve as a potential prognostic biomarker for predicting recurrence in early stage lung adenocarcinoma after curative surgery.
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Humans , Adenocarcinoma , Disease-Free Survival , Gene Expression , Lung Neoplasms , Lung , MicroRNAs , Polymerase Chain Reaction , Recurrence , RNA, Small UntranslatedABSTRACT
Unfortunately, the online published article has error in Figure 3.
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BACKGROUND AND PURPOSE: The anti-John-Cunningham virus (JCV)-antibody serostatus and index are used in the risk stratification of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with natalizumab. However, little information on these parameters is available for Asian countries. The purpose of this study was to determine the rate of seropositivity, index, and longitudinal index evolution in Korean patients with MS. METHODS: The antibody seroprevalence was analyzed in 355 samples from 187 patients with clinically isolated syndrome or MS using a second-generation, two-step, enzyme-linked immunosorbent assay. A 4-year longitudinal evaluation was applied to 66 patients. RESULTS: The overall antibody seroprevalence was 80% (n=149). Among antibody-positive patients, the index had a median value of 3.27 (interquartile range, 1.52–4.18), with 77% (n=114) and 56% (n=83) of patients having indices >1.5 and >3.0, respectively. The serostatus of 59 (89%) of the 66 patients did not change during the longitudinal analysis, while 3 (6%) of the 53 patients who were initially seropositive reverted to seronegativity, and 2 (15%) of the 13 patients who were initially seronegative converted to seropositivity. All patients with a baseline index >0.9 maintained seropositivity, and 92% of patients with a baseline index >1.5 maintained this index over 4 years. No patients developed PML (median disease duration, 8 years). CONCLUSIONS: The seroprevalence and index of anti-JCV antibodies in Korean patients with MS may be higher than those in Western countries.