The incidence and prevalence of inflammatory bowel diseases (IBDs) including ulcerative colitis and Crohn disease are rapidly increasing in Western countries and in developed Asian countries. Although biologic agents targeting the immune system have been effective in patients with IBD, cessation of treatment leads to relapse in the majority of patients, suggesting that intrinsic immune dysregulation is an effect, not a cause, of IBD. Dramatic changes in the environment, resulting in the dysregulated composition of intestinal microbiota or dysbiosis, may be associated with the fundamental causes of IBD. Japan now has upgraded water supply and sewerage systems, as well as dietary habits and antibiotic overuse that are similar to such features found in developed Western countries. The purpose of this review article was to describe the association of diet, particularly Japanese food and microbiota, with IBD.

Chronic kidney disease (CKD) has been recognized as a significant global health problem because of the increased risk of total and cardiovascular morbidity and mortality. Vitamin D deficiency or insufficiency is common in patients with CKD, and serum levels of vitamin D appear to have an inverse correlation with kidney function. Growing evidence has indicated that vitamin D deficiency may contribute to deteriorating renal function, as well as increased morbidity and mortality in patients with CKD. Recent studies have suggested that treatment with active vitamin D or its analogues can ameliorate renal injury by reducing fibrosis, apoptosis, and inflammation in animal models; this treatment also decreases proteinuria and mortality in patients with CKD. These renoprotective effects of vitamin D treatment are far beyond its classical role in the maintenance of bone and mineral metabolism, in addition to its pleiotropic effects on extramineral metabolism. In this review, we discuss the altered metabolism of vitamin D in kidney disease, and the potential renoprotective mechanisms of vitamin D in experimental and clinical studies. In addition, issues regarding the effects of vitamin D treatment on clinical outcomes are discussed.

Background/Aims: To evaluate the long-term efficacy and safety of endoscopic injection of N-butyl-2-cyanoacrylate (NBC; Histoacryl) for treatment of bleeding gastric varices. Methods: We retrospectively analyzed the records of 455 patients with gastric variceal hemorrhage (GVH) who were consecutively treated with NBC from January 2004 to July 2013, with a mean follow-up period of 582 days. The patients' endoscopic findings, initial hemostasis, complications, rebleeding rates, and bleeding-related death rates were reviewed. Results: Hemostasis was achieved initially in 96.9% (441/455) of patients; rebleeding occurred in 35.2% (160/455), and the bleeding-related death rate was 6.8% (31/455) during follow-up. Complications included fever (6.8%), abdominal pain (3.7%), diarrhea (1.3%), spontaneous bacterial peritonitis (0.7%), bacteremia (0.4%), and embolism (0.2%). A red-color sign on concomitant esophageal varices (EVs) (p = 0.002) and previous history of variceal bleeding (p < 0.001) were significant risk factors for rebleeding within 1 year. The Child-Pugh score (p < 0.001), presence of hepatocellular carcinoma (p = 0.001), and failure of initial hemostasis (p < 0.001) were the risk factors most closely associated with bleeding-related death. Conclusions: This study provides a comprehensive overview of the outcomes and prognostic factors of patients with GVH. The results may help in the selection of effective treatment strategies for patients with GVH.

Background/Aims: There are few data on the effects of low hemoglobin levels on the left ventricle (LV) in patients without heart disease. The objective of this study was to document changes in the echocardiographic variables of LV structure and function after the correction of anemia without significant cardiovascular disease. Methods: In total, 34 iron-deficiency anemia patients ($35{\pm}11$ years old, 32 females) without traditional cardiovascular risk factors or cardiovascular disease and 34 age- and gender-matched controls were studied. Assessments included history, physical examination, and echocardiography. Of the 34 patients with anemia enrolled, 20 were followed and underwent echocardiography after correction of the anemia. Results: There were significant differences between the anemia and control groups in LV diameter, left ventricular mass index (LVMI), left atrial volume index (LAVI), peak mitral early diastolic (E) velocity, peak mitral late diastolic (A) velocity, E/A ratio, the ratio of mitral to mitral annular early diastolic velocity (E/E'), stroke volume, and cardiac index. Twenty patients underwent follow-up echocardiography after treatment of anemia. The follow-up results showed significant decreases in the LV end-diastolic and end-systolic diameters and LVMI, compared with baseline levels. LAVI, E velocity, and E/E' also decreased, suggesting a decrease in LV filling pressure. Conclusions: Low hemoglobin level was associated with larger cardiac chambers, increased LV, mass and higher LV filling pressure even in the subjects without cardiovascular risk factors or overt cardiovascular disease. Appropriate correction of anemia decreased LV mass, LA volume, and E/E'.

Background/Aims: The aim of the present study was to evaluate the relationship between thyroid hormone levels and infarct severity in patients with ST-elevation myocardial infarction (STEMI). Methods: We retrospectively reviewed thyroid hormone levels, infarct severity, and the extent of transmurality in 40 STEMI patients evaluated via contrast-enhanced cardiac magnetic resonance imaging. Results: The high triiodothyronine ($T_3$) group (${\geq}68.3ng/dL$) exhibited a significantly higher extent of transmural involvement (late transmural enhancement > 75% after administration of gadolinium contrast agent) than did the low $T_3$ group (60% vs. 15%; p = 0.003). However, no significant difference was evident between the high- and low-thyroid-stimulating hormone/free thyroxine ($FT_4$) groups. When the $T_3$ cutoff level was set to 68.3 ng/dL using a receiver operating characteristic curve, the sensitivity was 80% and the specificity 68% in terms of differentiating between those with and without transmural involvement. Upon logistic regression analysis, high $T_3$ level was an independent predictor of transmural involvement after adjustment for the presence of diabetes mellitus (DM) and the use of glycoprotein IIb/IIIa inhibitors (odds ratio, 40.62; 95% confidence interval, 3.29 to 502; p = 0.004). Conclusions: The $T_3$ level predicted transmural involvement that was independent of glycoprotein IIb/IIIa inhibitor use and DM positivity.

Background/Aims: Gastroesophageal reflux disease is one of the most common causes of chronic cough and is a potential risk factor for the exacerbation of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the prevalence and risk factors for reflux esophagitis (RE) in COPD patients. Methods: From our hospital database, between September 2006 and April 2010, we searched for subjects who were 40 years old or older and had undergone both postbronchodilator spirometry and esophagogastroduodenoscopy (EGD). COPD was defined as having a ratio of forced expiratory volume in 1 second to forced vital capacity < 0.7 in postbronchodilator spirometry and no abnormality causing airway obstruction, except emphysematous changes, on a chest X-ray. The diagnosis of RE was based on a mucosal break surrounding the distal esophageal sphincter through EGD. Results: In total, 253 patients with COPD were enrolled. The prevalence of RE in COPD was 30% (76/253). Multiple logistic regression analyses revealed that age (odds ratio [OR], 0.950; 95% confidence interval [CI], 0.918 to 0.983; p = 0.003), smoking pack-years (OR, 1.015; 95% CI, 1.004 to 1.025; p = 0.006), and inhaled anticholinergics (OR, 0.516; 95% CI, 0.271 to 0.982; p = 0.044) were independently associated with RE in COPD patients. Conclusions: The prevalence of RE in our COPD patients was higher than that reported previously in the Korean general population. In COPD, smoking increased the risk of RE, whereas inhaled anticholinergics may be associated with a reduced risk of RE.

Background/Aims: 5'-Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a cellular energy sensor that monitors intracellular AMP/adenosine triphosphate (ATP) ratios and is a key regulator of the proliferation and survival of diverse malignant cell types. In the present study, we investigated the effect of activating AMPK by 5-aminoimidazole-4-carboxamide-ribonucleotide (AICAR) in thyroid cancer cells. Methods: We used FRO thyroid cancer cells harboring the $BRAF^{V600E}$ mutation to examine the effect of AICAR on cell proliferation and cell survival. We also evaluated the involvement of mitogen-activated protein kinase (MAPK) pathways in this effect. Results: We found that AICAR treatment promoted AMPK activation and suppressed cell proliferation and survival by inducing p21 accumulation and activating caspase-3. AICAR significantly induced activation of p38 MAPK, and pretreatment with SB203580, a specific inhibitor of the p38 MAPK pathway, partially but significantly rescued cell survival. Furthermore, small interfering RNA targeting AMPK-${\alpha}1$ abolished AICAR-induced activation of p38 MAPK, p21 accumulation, and activation of caspase-3. Conclusions: Our findings demonstrate that AMPK activation using AICAR inhibited cell proliferation and survival by activating p38 MAPK and proapoptotic molecules in FRO thyroid cancer cells. These results suggest that the AMPK and p38 MAPK signaling pathways may be useful therapeutic targets to treat thyroid cancer.

Background/Aims: Recurrent focal segmental glomerulosclerosis (FSGS) following renal transplantation is relatively common. However, the risk factors and optimal pretransplant treatment preventing recurrence of FSGS remain controversial. Methods: We retrospectively reviewed 27 adult renal transplant recipients with FSGS over a period of 10 years. We first compared possible risk factors for FSGS recurrence between the recurrence and nonrecurrence groups. Then we evaluated the effect of pretransplant plasmapheresis (PP; n = 4) and PP with rituximab (PP + RTX; n = 5) on recurrence of FSGS after transplantation compared to control patients that were not treated with these modalities. Results: There were seven recurrences in 27 patients (25.9%), but there were no significant differences in possible risk factors for FSGS recurrence between the two groups. Recurrence rates between patients with pretransplant PP or PP + RTX and control patients were not significantly different (22.2% vs. 27.7%, p > 0.05). There was also no significant difference in recurrence between the pretransplant PP and PP + RTX groups (25% vs. 20%, p > 0.05). Conclusions: Pretransplant PP or PP + RTX do not significantly decrease the recurrence of FSGS in adult renal transplant candidates.

Background/Aims: Inflammation is an important factor in renal injury. Ferritin, an inflammatory marker, is considered an independent predictor of rapid renal progression in patients with chronic kidney disease. However, the relationship between ferritin and residual renal function (RRF) in patients undergoing peritoneal dialysis (PD) remains unclear. Methods: We reviewed the medical records of patients who started PD between June 2001 and March 2012 at Soonchunhyang University Bucheon Hospital, Korea. A total of 123 patients were enrolled in the study. At 1 month after the initiation of PD, RRF was determined by a 24-hour urine collection and measured every 6 months thereafter. Clinical and biochemical data at the time of the initial 24-hour urine collection were considered as baseline. Results: The RRF reduction rate was significantly greater in patients with high ferritin (ferritin ${\geq}250ng/mL$) compared with those with low ferritin (ferritin < 250 ng/mL;$-1.71{pm}1.36mL$/min/yr/$1.73m^2$ vs. $-0.84{pm}1.63mL$/min/yr/$1.73m^2$, respectively; p = 0.007). Pearson correlation analysis revealed a significant negative correlation between the baseline serum ferritin level and the RRF reduction rate (r = -0.219, p = 0.015). Using multiple linear regression analysis and adjusting for other risk factors, baseline serum ferritin was an independent factor for the RRF reduction rate (${\beta}$ = -0.002, p = 0.002). Conclusions: In this study we showed that a higher ferritin level was significantly associated with a more rapid RRF decline in patients undergoing PD.

Background/Aims: Recently, many cases of vitamin K-dependent coagulopathy of unknown origin have been reported. Such patients lack any relevant family history and have no systemic disease, raising suspicion of superwarfarin intoxication. We evaluated individual risk factors causing coagulopathy and hemorrhagic symptoms in patients with suspected superwarfarin intoxication. In addition, we determined how to effectively treat vitamin K-dependent coagulopathy caused by suspected superwarfarin intoxication. Methods: Seven patients with suspected superwarfarin intoxication who lacked any definitive history of rodenticide ingestion were included. Thirty-one patients initially diagnosed with rodenticide poisoning were also included. We performed a retrospective chart review of all subjects and examined clinical data including patient demographics and medical histories. Results: Patients initially diagnosed with rodenticide poisoning were divided into two groups, one of which had a laboratory abnormality (prothrombin time [PT]> 13 seconds) and another group with PTs in the normal range. There was no significant difference between the two groups in any of age, gender, the extent of chronic alcohol consumption, the causative rodenticide, psychiatric problems, ingestion of drugs interacting with warfarin, the extent of intoxication, or the type of ingestion attempt. The albumin level of the former group was significantly lower than that of the latter group (p = 0.014). Furthermore, a significant difference between the two groups was evident in terms of simultaneous ingestion of rodenticide and alcohol (p = 0.023). Conclusions: Most patients with superwarfarin poisoning did not exhibit any complication. When such complications were evident, they were associated with serum albumin level and coingestion of rodenticide and alcohol.

Background/Aims: We investigated diff erences in identifying candidates for antiosteoporotic treatment in rheumatoid arthritis (RA) patients according to two available clinical guidelines. Methods: We prospectively enrolled 100 female patients aged 50 years or older with RA who visited Hanyang University Hospital for periodic examinations between April 2011 and August 2011. We applied the glucocorticoid-induced osteoporosis (GIOP) recommendations and the National Osteoporosis Foundation (NOF) guidelines to RA patients and examined agreement between the guidelines for identifying candidates for antiosteoporotic treatment. We also analyzed the impact of screening vertebral fractures (VFs) in determining the treatment of osteoporosis in RA patients. Results: The 57 patients taking glucocorticoids were classifi ed into high-risk (n = 23), medium-risk (n = 16), and low-risk (n = 18) groups according to the GIOP recommendations. Based on the NOF guidelines, 36 of 57 patients were candidates for antiosteoporotic treatment and the agreement between two guidelines was high (${\kappa}$ = 0.76). Two of the 18 patients in the low-risk group and 19 of 43 patients not eligible per the GIOP recommendations were classifi ed as candidates for antiosteoporotic treatment by the NOF guidelines. Conclusions: In determining antiosteoporotic treatment for RA patients, using only the GIOP recommendations is insuffi cient. Application of the NOF guidelines in patients not eligible for or classifi ed into the low-risk group per the GIOP recommendations and screening for VFs may be helpful in deciding on antiosteoporotic treatment in RA patients.

Background/Aims: Increased resting energy expenditure (REE) in rheumatoid arthritis (RA) patients is thought to be caused by hypermetabolism associated with production of proinflammatory cytokines. Our aim in the present study was to explore the possible association between REE and disease activity in females with RA. Methods: A total of 499 female RA patients were recruited to this cross-sectional study assessing REE scores on disease activity indices (the routine assessment of patient index data 3 [RAPID3], the disease activity score 28, and the clinical/simplified disease activity index [CDAI/SDAI]) and the levels of RA-associated autoantibodies (rheumatoid factor and anticyclic citrullinated peptide [anti-CCP] antibodies). Age-matched healthy female controls (n = 131) were also enrolled. Results: REE did not differ between RA patients (all patients, and those in remission or not) and controls, or between RA patients in remission or not (p > 0.05 for all comparisons). Increased REE in total RA patients was associated with younger age and a higher body mass index (BMI) (p < 0.001 and p < 0.001, respectively), but not with disease activity index scores on any of RAPID3, CDAI, or SDAI. BMI was the only clinical parameter exhibiting a significant relationship with REE quartiles (Q1 to Q4; p < 0.001); none of disease duration, functional status, or anti-CCP antibody titer in RA patients was significantly related to REE, based on analysis of covariance. Conclusions: We found no association between REE and disease activity in RA patients, implying that energy metabolism in RA patients might be independent of RA-associated systemic inflammation.