Background/Aims: The long-term course of Crohn’s disease (CD) has never been evaluated in non-Caucasian population-based cohorts. The aim of the present study was to evaluate the longterm prognosis of Korean CD patients in the well-defined population-based Songpa-Kangdong inflammatory bowel disease cohort. Methods: Outcomes of disease and their predictors were evaluated for 418 patients diagnosed with CD between 1986 and 2015. Results: During a median of 123 months, systemic corticosteroids, thiopurines, and anti-tumor necrosis factor (TNF) agents were administered to 58.6%, 81.3%, and 37.1% of patients, respectively. Over time, the cumulative probability of starting corticosteroids significantly decreased (p=0.001), whereas that of starting thiopurines and anti-TNFs significantly increased (both p<0.001). The cumulative probability of behavioral progression was 54.5% at 20 years, and it significantly decreased during the anti-TNF era. Intestinal resection was required for 113 patients (27.0%). The cumulative probabilities of intestinal resection at 1, 5, 10, 20, and 25 years after CD diagnosis were 12.7%, 16.5%, 23.8%, 45.1%, and 51.2%, respectively. Multivariable Cox regression analysis identified stricturing behavior at diagnosis (adjusted hazard ratio [aHR], 2.70; 95% confidence interval [CI], 1.55 to 4.71), penetrating behavior at diagnosis (aHR, 11.15; 95% CI, 6.91 to 17.97), and diagnosis of CD during the anti-TNF era (aHR, 0.51; 95% CI, 0.35 to 0.76) as independently associated with intestinal resection. The standardized mortality ratio among CD patients was 1.36 (95% CI, 0.59 to 2.68). Conclusions The long-term prognosis of Korean patients with CD is at least as good as that of Western CD patients, as indicated by the low intestinal resection rate. Moreover, behavioral progression and intestinal resection rates have decreased over the past 3 decades.

Background/Aims: We aimed to evaluate the clinical characteristics and long-term prognosis of elderly-onset ulcerative colitis (EOUC) in Korean patients over a 30-year period using a wellestablished population-based cohort in the Songpa-Kangdong district of Seoul, Korea. Methods: Clinical characteristics and prognosis were compared between two groups: EOUC,defined as UC diagnosed in individuals aged ≥60 years and non-EOUC (N-EOUC), defined asUC diagnosed in individuals aged 18 to 59 years. Results: We identified 99 patients with EOUC (10.3%) and 866 patients with N-EOUC (89.7%) between 1986 and 2015. During the median follow-up of 104.5 months, the overall exposure tomedications was comparable between patients with EOUC and N-EOUC (p=0.091 for corticosteroids, p=0.794 for thiopurines, and p=0.095 for anti-tumor necrosis factor agents). The cumula-tive risks of disease outcomes were also comparable between patients with EOUC and N-EOUC (22.4% vs 30.4% for proximal disease extension [p=0.351], 11.9% vs 18.1% for hospitalization [p=0.240], and 2.3% vs 1.8% for colectomy [p=0.977]) at 10 years after diagnosis. Multivariate Cox regression analysis revealed that corticosteroid use at diagnosis was an independent predic-tor of proximal disease extension (hazard ratio [HR], 6.216; 95% confidence interval [CI], 1.314 to 28.826) and hospitalization (HR, 11.241; 95% CI, 3.027 to 41.742) in patients with EOUC. Conclusions In this population-based study from Korea, the pattern of medication use seemed comparable between the EOUC and N-EOUC groups. Moreover, patients with EOUC and those with N-EOUC have a similar disease course in terms of proximal disease extension, hospitaliza-tion, and colectomy.

Background/Aims: We aimed to evaluate the clinical characteristics and long-term prognosis of elderly-onset ulcerative colitis (EOUC) in Korean patients over a 30-year period using a wellestablished population-based cohort in the Songpa-Kangdong district of Seoul, Korea. Methods: Clinical characteristics and prognosis were compared between two groups: EOUC,defined as UC diagnosed in individuals aged ≥60 years and non-EOUC (N-EOUC), defined asUC diagnosed in individuals aged 18 to 59 years. Results: We identified 99 patients with EOUC (10.3%) and 866 patients with N-EOUC (89.7%) between 1986 and 2015. During the median follow-up of 104.5 months, the overall exposure tomedications was comparable between patients with EOUC and N-EOUC (p=0.091 for corticosteroids, p=0.794 for thiopurines, and p=0.095 for anti-tumor necrosis factor agents). The cumula-tive risks of disease outcomes were also comparable between patients with EOUC and N-EOUC (22.4% vs 30.4% for proximal disease extension [p=0.351], 11.9% vs 18.1% for hospitalization [p=0.240], and 2.3% vs 1.8% for colectomy [p=0.977]) at 10 years after diagnosis. Multivariate Cox regression analysis revealed that corticosteroid use at diagnosis was an independent predic-tor of proximal disease extension (hazard ratio [HR], 6.216; 95% confidence interval [CI], 1.314 to 28.826) and hospitalization (HR, 11.241; 95% CI, 3.027 to 41.742) in patients with EOUC. Conclusions In this population-based study from Korea, the pattern of medication use seemed comparable between the EOUC and N-EOUC groups. Moreover, patients with EOUC and those with N-EOUC have a similar disease course in terms of proximal disease extension, hospitaliza-tion, and colectomy.

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. METHODS: A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids. RESULTS: A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals. CONCLUSIONS: The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.
Acetaminophen ; Acetates ; Acetic Acid ; Anti-Inflammatory Agents, Non-Steroidal ; Cicatrix ; Classification ; Cyclooxygenase 2 Inhibitors ; Diethylpropion ; Drug Hypersensitivity ; Drug Hypersensitivity Syndrome ; Hospitals, University ; Incidence ; Korea ; Phenotype ; Propionates ; Prospective Studies ; Retrospective Studies ; Salicylates ; Salicylic Acid ; Stevens-Johnson Syndrome

Hepatic ischemia/reperfusion (I/R) injury leads to oxidative stress and acute inflammatory responses that cause liver damage and have a considerable impact on the postoperative outcome. Much research has been performed to develop possible protective techniques. We aimed to investigate the efficacy of SPA0355, a synthetic thiourea analog, in an animal model of hepatic I/R injury. Male C57BL/6 mice underwent normothermic partial liver ischemia for 45 min followed by varying periods of reperfusion. The animals were divided into three groups: sham operated, I/R and SPA0355 pretreated. Pretreatment with SPA0355 protected against hepatic I/R injury, as indicated by the decreased levels of serum aminotransferase and reduced parenchymal necrosis and apoptosis. Liver synthetic function was also restored by SPA0355 as reflected by the prolonged prothrombin time. To gain insight into the mechanism involved in this protection, we measured the activity of nuclear factor-kappaB (NF-kappaB), which revealed that SPA0355 suppressed the nuclear translocation and DNA binding of NF-kappaB subunits. Concomitantly, the expression of NF-kappaB target genes such as IL-1beta, IL-6, TNF-alpha and iNOS was significantly downregulated. Lastly, the liver antioxidant enzymes superoxide dismutase, catalase and glutathione were upregulated by SPA0355 treatment, which correlated with the reduction in serum malondialdehyde. Our results suggest that SPA0355 pretreatment prior to I/R injury could be an effective method to reduce liver damage.
Animals ; Anti-Inflammatory Agents/*therapeutic use ; Benzoxazines/*therapeutic use ; Liver/*drug effects/immunology/*injuries/pathology ; Male ; Mice, Inbred C57BL ; NF-kappa B/immunology ; Reperfusion Injury/*drug therapy/immunology/pathology ; Signal Transduction/drug effects ; Thiourea/*analogs & derivatives/therapeutic use

OBJECTIVE: The aim of this study was to document the natural course of asymptomatic adult moyamoya disease (MMD) and the factors related to disease progression to aid in treatment decisions. MATERIALS AND METHODS: Among 459 adult MMD patients (aged > or = 20 years), 42 patients were included in this retrospective cohort study. Clinical records of adult asymptomatic MMD patients (n = 42) and follow-up data from September 2013 were reviewed to determine the factors related to disease progression. RESULTS: The mean age of patients at the time of diagnosis was 41.2 years (range, 23-64 years), and the mean follow-up period was 37.3 months (range, 7.4-108.7 months). Of the 42 patients and 75 hemispheres, there were 12 patients (28.6%) and 13 hemispheres (17.3%) with disease progression. There were four hemispheres (5.3%) with symptomatic progression (three hemorrhage, one transient ischemic attack) and nine hemispheres (12.0%) with asymptomatic radiographic progression. There were no relationships with sex, diabetes, hypertension, thyroid disease, family history of MMD, or family history of stroke. However, reduced initial cerebrovascular reserve capacity was observed in seven hemispheres (9.3%) in patients with disease progression. A relationship was found between disease progression and initial cerebrovascular reserve capacity (p = 0.05). None of the patients underwent bypass surgery during the follow-up period. CONCLUSION: It appears that asymptomatic adult MMD is not a permanent stable disease. In particular, reduced cerebrovascular reserve capacity is an indication of MMD progression, so close regular observation is needed.
Adult* ; Asymptomatic Diseases ; Cerebrovascular Disorders ; Cohort Studies ; Diagnosis ; Disease Progression ; Follow-Up Studies ; Hemorrhage ; Humans ; Hypertension ; Moyamoya Disease* ; Retrospective Studies ; Stroke ; Thyroid Diseases

OBJECTIVE: Several studies have reported on the effectiveness of fronto-lateral craniotomy in reducing the operating time and post-operative complications. However, no study has practically evaluated this method from the cosmetic point of view. MATERIALS AND METHODS: We designed this study for comparison of the clinical differences and cosmetic outcomes between the frontolateral craniotomy and the conventional pterional craniotomy for clipping of unruptured intracranial aneurysms. We performed a retrospective analysis of the two groups based on their medical records and radiologic findings juxtaposed with their length of hospital stay, intensive care unit day and operation time, and the emergence of postoperative complication, mean size of aneurysm, and temporal depression. RESULTS: After careful comparison of the thickness of temporalis muscle between the craniotomy side and the contralateral side, the results clearly showed that the conventional pterional craniotomy group was asymmetric by a p value of 0.152 and the frontolateral craniotomy group was symmetric by a p value of 0.002. CONCLUSION: Frontolateral craniotomy could be a practical alternative for patients with an unruptured intracranial aneurysm in the anterior circulation including the posterior communicating artery, particularly those who are in a medically poor state or who highly demand minimal aesthetic mutilation.
Aneurysm* ; Arteries ; Craniotomy ; Depression ; Humans ; Intensive Care Units ; Intracranial Aneurysm ; Length of Stay ; Medical Records ; Postoperative Complications ; Retrospective Studies

Single nucleotide polymorphisms (SNPs) are the most abundant forms of human genetic variations and resources for mapping complex genetic traits and disease association studies. We have constructed a linkage disequilibrium(LD) map of chromosome 22 in Korean samples and compared it with those of other populations, including Yorubans in Ibadan, Nigeria (YRI), Centred'Etude du Polymorphisme Humain (CEPH) reference families (CEU), Japanese in Tokyo (JPT) and Han Chinese in Beijing (CHB) in the HapMap database. We genotyped 4681 of 111,448 publicly available SNPs in 90 unrelated Koreans. Among genotyped SNPs, 4167 were polymorphic. Three hundred and five LD blocks were constructed to make up 18.6% (6.4 of 34.5 Mb) of chromosome 22 with 757 tagSNPs and 815 haplotypes(frequency > or = 5.0%). Of 3430 common SNPs genotyped in all five populations, 514 were monomorphic in Koreans. The CHB + JPT samples have more than a 72% overlap with the monomorphic SNPs in Koreans, while the CEU + YRI samples have less than a 38% overlap. The patterns of hot spots and LD blocks were dispersed throughout chromosome 22, with some common blocks among populations, highly concordant between the three Asian samples. Analysis of the distribution of chimpanzee-derived allele frequency (DAF), a measure of genetic differentiation, Fst levels, and allele frequency difference (AFD) among Koreans and the HapMap samples showed a strong correlation between the Asians, while the CEU and YRI samples showed a very weak correlation with Korean samples. Relative distance as a quantitative measurement based upon DAF, Fst, and AFD indicated that all three Asian samples are very proximate, while CEU and YRI are significantly remote from the Asian samples. Comparative genome-wide LD studies provide useful information on the association studies of complex diseases.
Asian Continental Ancestry Group ; Chromosomes, Human, Pair 22 ; Gene Frequency ; Genetic Variation ; Haplotypes ; HapMap Project ; Humans ; Nigeria ; Polymorphism, Single Nucleotide ; Tokyo

Single nucleotide polymorphisms (SNPs) are the most abundant forms of human genetic variations and resources for mapping complex genetic traits and disease association studies. We have constructed a linkage disequilibrium(LD) map of chromosome 22 in Korean samples and compared it with those of other populations, including Yorubans in Ibadan, Nigeria (YRI), Centred'Etude du Polymorphisme Humain (CEPH) reference families (CEU), Japanese in Tokyo (JPT) and Han Chinese in Beijing (CHB) in the HapMap database. We genotyped 4681 of 111,448 publicly available SNPs in 90 unrelated Koreans. Among genotyped SNPs, 4167 were polymorphic. Three hundred and five LD blocks were constructed to make up 18.6% (6.4 of 34.5 Mb) of chromosome 22 with 757 tagSNPs and 815 haplotypes(frequency > or = 5.0%). Of 3430 common SNPs genotyped in all five populations, 514 were monomorphic in Koreans. The CHB + JPT samples have more than a 72% overlap with the monomorphic SNPs in Koreans, while the CEU + YRI samples have less than a 38% overlap. The patterns of hot spots and LD blocks were dispersed throughout chromosome 22, with some common blocks among populations, highly concordant between the three Asian samples. Analysis of the distribution of chimpanzee-derived allele frequency (DAF), a measure of genetic differentiation, Fst levels, and allele frequency difference (AFD) among Koreans and the HapMap samples showed a strong correlation between the Asians, while the CEU and YRI samples showed a very weak correlation with Korean samples. Relative distance as a quantitative measurement based upon DAF, Fst, and AFD indicated that all three Asian samples are very proximate, while CEU and YRI are significantly remote from the Asian samples. Comparative genome-wide LD studies provide useful information on the association studies of complex diseases.
Asian Continental Ancestry Group ; Chromosomes, Human, Pair 22 ; Gene Frequency ; Genetic Variation ; Haplotypes ; HapMap Project ; Humans ; Nigeria ; Polymorphism, Single Nucleotide ; Tokyo

BACKGROUND: This study compared the bronchodilator efficacy and safety of tiotropium inhalation capsules (18microgram once daily) with a ipratropium metered dose inhaler (2 puffs of 20microgram q.i.d.) in patients with chronic obstructive pulmonary disease (COPD). METHOD: After the initial screening assessment and a two-week run-in period, patients received either tiotropium 18microgram once daily or ipratropium 40microgram four times daily over a period of 4 weeks in a double blind, double dummy, parallel group study. The outcome measures were the lung function, the daily records of the peak expiratory flow rate (PEFR), the patients' questionnaire, and the use of concomitant salbutamol. The forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC) were measured 5 minutes before inhalation, and 0.5, 1, 2 and 3 hours after inhaling the study drug on days 0, 14 and 28. RESULT: In 16 centers, 134 patients with a mean (SD) age of 66 (7) years and a predicted FEV1 of 42 (12)% were analyzed. The trough FEV1 response was significantly higher in the tiotropium group than in the ipratropium group after a four-week treatment period. The weekly mean morning PEFR of the tiotropium group was consistently higher than that of the ipratropium group during the 4-week treatment period with differences ranging from 12.52 to 13.88 l/min, which were statistically significant. Tiotropium was well tolerated by the COPD patients during the 4-week treatment period and had a similar safety profile to ipratropium. CONCLUSION: This study shows that tiotropium administrated once daily has a superior bronchodilator effect with a similar safety profile in treating COPD patients compared with ipratropium, inhaled four times daily.
Adult* ; Albuterol ; Bronchodilator Agents ; Capsules ; Forced Expiratory Volume ; Humans ; Inhalation ; Ipratropium* ; Lung ; Mass Screening ; Metered Dose Inhalers ; Outcome Assessment (Health Care) ; Peak Expiratory Flow Rate ; Pulmonary Disease, Chronic Obstructive* ; Surveys and Questionnaires ; Vital Capacity ; Tiotropium Bromide