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.

BACKGROUND: From May to July 2015, the Republic of Korea experienced the largest outbreak of Middle East respiratory syndrome (MERS) outside the Arabian Peninsula. A total of 186 patients, including 36 deaths, had been diagnosed with MERS-coronavirus (MERS-CoV) infection as of September 30th, 2015. MATERIALS AND METHODS: We obtained information of patients who were confirmed to have MERS-CoV infection. MERS-CoV infection was diagnosed using real-time reverse-transcriptase polymerase chain reaction assay. RESULTS: The median age of the patients was 55 years (range, 16 to 86). A total of 55.4% of the patients had one or more coexisting medical conditions. The most common symptom was fever (95.2%). At admission, leukopenia (42.6%), thrombocytopenia (46.6%), and elevation of aspartate aminotransferase (42.7%) were observed. Pneumonia was detected in 68.3% of patients at admission and developed in 80.8% during the disease course. Antiviral agents were used for 74.7% of patients. Mechanical ventilation, extracorporeal membrane oxygenation, and convalescent serum were employed for 24.5%, 7.1%, and 3.8% of patients, respectively. Older age, presence of coexisting medical conditions including diabetes or chronic lung disease, presence of dyspnea, hypotension, and leukocytosis at admission, and the use of mechanical ventilation were revealed to be independent predictors of death. CONCLUSION: The clinical features of MERS-CoV infection in the Republic of Korea were similar to those of previous outbreaks in the Middle East. However, the overall mortality rate (20.4%) was lower than that in previous reports. Enhanced surveillance and active management of patients during the outbreak may have resulted in improved outcomes.
Antiviral Agents ; Aspartate Aminotransferases ; Coronavirus Infections* ; Disease Outbreaks ; Dyspnea ; Extracorporeal Membrane Oxygenation ; Fever ; Humans ; Hypotension ; Leukocytosis ; Leukopenia ; Lung Diseases ; Middle East Respiratory Syndrome Coronavirus ; Middle East* ; Mortality ; Pneumonia ; Polymerase Chain Reaction ; Republic of Korea* ; Respiration, Artificial ; Thrombocytopenia

BACKGROUND/AIMS: beta-Cell apoptosis caused by increased endoplasmic reticulum (ER) stress is an important pathogenic component of type 2 diabetes mellitus. In theory, sulfonylureas, used for the treatment of diabetes, can contribute to ER stress. We assessed changes in ER stress in pancreatic beta-cells under glucotoxic or glucolipotoxic conditions using low concentrations of the sulfonylurea, glibenclamide (GB). METHODS: Low concentrations of GB (10 or 100 nM) were added to INS-1 cells cultured under glucotoxic or glucolipotoxic conditions. The degree of viability, level of apoptosis and levels of markers associated with ER stress were measured. RESULTS: Apoptosis decreased in response to low concentrations of GB under glucolipotoxic but not glucotoxic conditions. Most ER stress markers decreased upon the addition of GB. Under glucotoxic conditions, changes in the levels of ER stress markers were not consistent. However, all decreased significantly under glucolipotoxic conditions. CONCLUSIONS: Low concentrations of GB exerted antiapoptotic effects through the attenuation of ER stress under glucolipotoxic conditions.
Animals ; Apoptosis/*drug effects ; Biological Markers/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects ; Diabetes Mellitus/drug therapy ; Endoplasmic Reticulum Stress/*drug effects ; Glyburide/*pharmacology/therapeutic use ; Hypoglycemic Agents/*pharmacology/therapeutic use ; Rats

BACKGROUND: beta-cell death due to endoplasmic reticulum (ER) stress has been regarded as an important pathogenic component of type 2 diabetes. The possibility has been suggested that sulfonylurea, currently being used as one of the main oral hypoglycemic agents of type 2 diabetes, increases ER stress, which could lead to sulfonylurea failure. The authors of the present study examined ER stress of beta-cells in a glucolipotoxic condition using glyburide (GB) in an environment mimicking type 2 diabetes. METHODS: Apoptosis was induced by adding various concentrations of GB (0.001 to 200 microM) to a glucolipotoxic condition using 33 mM glucose, and the effects of varied concentrations of palmitate were evaluated via annexin V staining. The markers of ER stress and pro-apoptotic markers were assessed by Western blotting and semi-quantitative reverse transcription-polymerase chain reaction. Additionally, the anti-apoptotic markers were evaluated. RESULTS: Addition of any concentration of GB in 150 microM palmitate and 33 mM glucose did not increase apoptosis. The expression of phosphorylated eukaryotic initiation factor (eIF-2alpha) was increased and cleaved caspase 3 was decreased by adding GB to a glucolipotoxic condition. However, other ER stress-associated markers such as Bip-1, X-box binding protein-1, ATF-4 and C/EBP-homologous protein transcription factor and anti-apoptotic markers phosphor-p85 phosphatidylinositol 3-kinase and phosphorylation of Akt did not change significantly. CONCLUSION: GB did not show further deleterious effects on the degree of apoptosis or ER stress of INS-1 cells in a glucolipotoxic condition. Increased phosphorylation of eIF-2alpha may attenuate ER stress for adaptation to increased ER protein load.
Annexin A5 ; Apoptosis ; Blotting, Western ; Caspase 3 ; Endoplasmic Reticulum ; Endoplasmic Reticulum Stress ; Eukaryotic Initiation Factor-2 ; Glucose ; Glyburide ; Hypoglycemic Agents ; Insulin-Secreting Cells ; Peptide Initiation Factors ; Phosphatidylinositol 3-Kinase ; Phosphorylation ; Transcription Factors

BACKGROUND/AIMS: Xanthogranulomatous cholecystitis (XGC) mimics early-stage gallbladder (GB) cancer with wall thickening on computed tomography (CT), both clinically and radiologically. Preoperative differentiation of XGC from early-stage GB cancer is important for selecting the most appropriate surgical management. Therefore, we evaluated the clinical features and multidetector CT (MDCT) findings of XGC to determine whether it can be distinguished from early-stage GB cancer. METHODS: We retrospectively evaluated 25 patients with XGC and 56 patients with the wall-thickening type of T1- and T2-stage GB cancer, where all of the diagnoses were pathologically confirmed by surgical treatment. All of the patients underwent preoperative MDCT. The clinical symptoms, laboratory findings, and CT findings were compared. RESULTS: Abdominal pain, fever, and jaundice were noted more frequently in the patients with XGC. Serum aspartate aminotransferase and alanine aminotransferase levels were more elevated in patients with XGC, whereas carbohydrate antigen (CA 19-9) was higher in the patients with GB cancer. When the T-category cancer staging of XGC and early-stage GB cancer were compared, diffuse GB wall thickening, intramural hypoattenuated nodule, gallstone, and pericholecystic infiltration were consistent significant findings associated with XGC, regardless of the cancer staging. CONCLUSIONS: MDCT findings such as diffuse GB wall thickening, intramural hypoattenuated nodule, gallstone, and pericholecystic infiltration together with the clinical symptoms, can provide clues for physicians to differentiate XGC from early-stage GB cancer with wall thickening on CT.
Abdominal Pain ; Alanine Transaminase ; Aspartate Aminotransferases ; Cholecystitis ; Fever ; Gallbladder ; Gallbladder Neoplasms ; Gallstones ; Granuloma ; Humans ; Jaundice ; Multidetector Computed Tomography ; Neoplasm Staging ; Retrospective Studies ; Xanthomatosis

Primary cardiac lymphomas (PCL) are extremely rare. Clinical manifestations may be variable and are attributed to location. Here, we report on a case of PCL presenting with atrioventricular (AV) block. A 55 year-old male had experienced chest discomfort with unexplained dyspnea and night sweating. His initial electrocardiogram (ECG) revealed a first degree AV block. Along with worsening chest discomfort and dyspnea, his ECG changed to show second degree AV block (Mobitz type I). Computed tomography (CT) scan showed a cardiac mass (about 7 cm) and biopsy was performed. Pathologic finding confirmed diffuse large B-cell lymphoma. The patient was treated with multi-drug combination chemotherapy (R-CHOP: Rituximab, cyclophoshamide, anthracycline, vincristine, and prednisone). After treatment, ECG changed to show normal sinus rhythm with complete remission on follow-up CT scan.
Antibodies, Monoclonal, Murine-Derived ; Atrioventricular Block ; Biopsy ; Drug Therapy, Combination ; Dyspnea ; Electrocardiography ; Follow-Up Studies ; Heart Neoplasms ; Humans ; Lymphoma ; Lymphoma, B-Cell ; Lymphoma, Large B-Cell, Diffuse ; Male ; Sweat ; Sweating ; Thorax ; Vincristine ; Rituximab

BACKGROUND: Blood glucose level continuously fluctuates within a certain range in the human body. In diabetes patients, the extent of such fluctuation is large, despite the strict control of blood glucose. Blood glucose fluctuation has been shown to mediate more adverse effects on vascular endothelial cells and diabetes complications than chronic hyperglycemia, which has been explained as due to oxidative stress. As few previous studies have reported the effects of chronic and intermittent hyperglycemia on the apoptosis and function of pancreatic beta cells, this study reported herein was performed to investigate such effects on these cells. METHODS: For chronic hyperglycemia, INS-1 cells were cultured for 5 days with changes of RPMI 1640 medium containing 33 mM glucose every 12 hours. For intermittent hyperglycemia, the medium containing 11 mM glucose was exchanged with the medium containing 33 mM glucose every 12 hours. Apoptosis was assessed by TUNEL assay Hoechst staining and cleaved caspase 3. Insulin secretory capacity was assessed, and the expression of Mn-SOD and Bcl-2 was measured by Western blotting. RESULTS: In comparison to the control group, INS-1 cells exposed to chronic hyperglycemia and intermittent hyperglycemia showed an increase in apoptosis. The apoptosis of INS-1 cells exposed to intermittent hyperglycemia increased significantly more than the apoptosis of INS-1 cells exposed to chronic hyperglycemia. In comparison to the control group, the insulin secretory capacity in the two hyperglycemic states was decreased, and more with intermittent hyperglycemia than with chronic hyperglycemia. The expression of Mn-SOD and Bcl-2 increased more with chronic hyperglycemia than with intermittent hyperglycemia. CONCLUSION: Intermittent hyperglycemia induced a higher degree of apoptosis and decreased the insulin secretory capacity more in pancreatic beta cells than chronic hyperglycemia. This activity may be mediated by the anti-oxidative enzyme Mn-SOD and the anti-apoptotic signal Bcl-2.
Apoptosis ; Blood Glucose ; Blotting, Western ; Caspase 3 ; Diabetes Complications ; Endothelial Cells ; Glucose ; Human Body ; Humans ; Hyperglycemia ; In Situ Nick-End Labeling ; Insulin ; Insulin-Secreting Cells ; Oxidative Stress ; Superoxide Dismutase

PURPOSE: Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme regulating folate level, which affects DNA synthesis and methylation. MTHFR is highly polymorphic, and its variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level. Generally, a low folate level is known to be associated with a gastrointestinal neoplasm. Three common single nucleotide polymorphisms (SNPs) resulting in amino-acid changes (C677T, A1298C and G1793A) have been reported in MTHFR. We studied the relationship of MTHFR C677T, A1298C and G1793A polymorphisms between from colon cancer group and control group of Korean people. METHODS: We performed a case- control study to examine the relationship between MTHFR C677, A1298C, and G1793A polymorphisms and the risk of colon cancer. Two hundred seven (207) individuals with colon cancer and 288 healthy persons were analyzed. Blood sampling of each group was performed, and (PCR-RFLP) was analyzed; as a result, MTHFR polymorphism genotypes were obtained. RESULTS: The genotype frequencies of MTHFR C677T polymorphisms were 27.1% (CC), 48.3% (CT), 24.6% (TT), and 72.9% (CT+TT) in the patient group and 39.2% (CC), 36.8% (CT), 24.0% (TT), and 60.8% (CT+TT) in the control group. The genotype frequencies of MTHFR A1298C polymorphisms were 58% (AA), 35.7% (AC), 6.3% (CC), and 42% (AC+CC) in the patient group and 55.6% (AA), 40.3% (AC), 4.2% (CC), and 44.4% (AC+CC) in control group. The genotype frequencies of MTHFR G1793A polymorphisms were 83% (GG), 15.9% (GA), 1% (AA), and 16.9% (GA+AA) in the patient group and 85.8% (GG), 11.8% (GA), 2.4% (AA), and 14.2% (GA+AA) in the control group. The 677CT genotype was associated with a significantly increased risk for colon cancer (adjusted OR=1.90, 95% confidence interval: 1.25~2.90 in CT) than the 677CC genotype. The 1298CC, 1298AC, 1793AA, and 1793GA genotypes were not associated with a significantly increased risk for colon cancer. CONCLUSIONS: The MTHFR C677T polymorphism may influence colon cancer, but the MTHFR A1298C and G1793A polymorphisms need to be studied further for careful interpretation and confirmation in larger studies.
Colon ; Colonic Neoplasms ; DNA ; Folic Acid ; Gastrointestinal Neoplasms ; Genotype ; Humans ; Methylation ; Methylenetetrahydrofolate Reductase (NADPH2) ; Plasma ; Polymorphism, Single Nucleotide