Although ileocolonoscopy is the gold standard for diagnosis of inflammatory bowel disease and is useful for assessing the disease severity in the colon and terminal ileum, several alternative diagnostic techniques have been developed recently. For ulcerative colitis (UC), magnification colonoscopy, endocytoscopy, and confocal laser endomicroscopy enable assessment of histological inflammation without the need for biopsy. Capsule endoscopy is useful for detection of small intestinal and colonic lesions in both female and male patients. For UC, capsule endoscopy may be useful for evaluating colonic inflammation in patients with a previous poor colonoscopy experience, while it should be used only in Crohn's disease (CD) patients with unexplained symptoms when other examinations are negative. Magnetic resonance enterography (MRE) is particularly useful for detecting transmural inflammation, stenosis, and extraintestinal lesions, including abscesses and fistulas. MRE is also useful when evaluating small and large intestinal lesions, even in cases with severe strictures in which full evaluation of the small bowel would be virtually impossible using other devices. Therefore, the appropriate diagnostic devices for detecting CD lesions in the small and large intestine should be used.

Bone is a unique organ composed of mineralized hard tissue, unlike any other body part. The unique manner in which bone can constantly undergo self-remodeling has created interesting clinical approaches to the healing of damaged bone. Healing of large bone defects is achieved using implant materials that gradually integrate with the body after healing is completed. Such strategies require a multidisciplinary approach by material scientists, biological scientists, and clinicians. Development of materials for bone healing and exploration of the interactions thereof with the body are active research areas. In this review, we explore ongoing developments in the creation of materials for regenerating hard tissues.

Human genetic variation is represented by the genetic differences both within and among populations, and most genetic variants do not cause overt diseases but contribute to disease susceptibility and influence drug response. During the last century, various genetic variants, such as copy number variations (CNVs), have been associated with diverse human disorders. Here, we review studies on the associations between CNVs and autoimmune diseases to gain some insight. First, some CNV loci are commonly implicated in various autoimmune diseases, such as $Fc{\gamma}$ receptors in patients with systemic lupus erythemoatosus or idiopathic thrombocytopenic purpura and ${\beta}-defensin$ genes in patients with psoriasis or Crohn's disease. This means that when a CNV locus is associated with a particular autoimmune disease, we should examine its potential associations with other diseases. Second, interpopulation or interethnic differences in the effects of CNVs on phenotypes exist, including disease susceptibility, and evidence suggests that CNVs are important to understand susceptibility to and pathogenesis of autoimmune diseases. However, many findings need to be replicated in independent populations and different ethnic groups. The validity and reliability of detecting CNVs will improve quickly as genotyping technology advances, which will support the required replication.

Background/Aims: $^{18}F-Fluorodeoxyglucose$ positron-emission tomography ($^{18}F-FDG$ PET) has been used to assess the biological behavior of hepatocellular carcinoma (HCC). In this study, we investigated the usefulness of $^{18}F-FDG$ PET for predicting tumor progression and survival in patients with intermediate Barcelona Clinic Liver Cancer (BCLC) intermediate-stage HCC treated by transarterial chemoembolization (TACE). Methods: From February 2006 to March 2013, 210 patients treated with TACE, including 77 patients with BCLC intermediate-stage HCC, underwent examination by $^{18}F-FDG$ PET. $^{18}F-FDG$ uptake was calculated based on the tumor maximum (Tmax) standardized uptake value (SUV), the liver mean (Lmean) SUV, and the ratio of the Tmax SUV to the Lmean SUV (Tmax/Lmean). Results: The mean follow-up period for the 77 patients (52 males, 25 females; average age, 63.3 years) was 22.2 months. The median time to progression of HCC in patients with a low Tmax/Lmean (< 1.83) and high Tmax/Lmean (${\geq}1.83$) was 17 and 6 months, respectively (p < 0.001). The median overall survival time of patients with a low and high Tmax/Lmean was 44 and 14 months, respectively (p = 0.003). Multivariate analysis revealed that the Tmax/Lmean was an independent predictor of overall survival (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.210 to 3.156; p = 0.006) and tumor progression (HR, 2.05; 95% CI, 1.264 to 3.308; p = 0.004). Conclusions: $^{18}F-FDG$ uptake calculated by the Tmax/Lmean using PET predicted tumor progression and survival in patients with BCLC intermediate-stage HCC treated by TACE.

Background/Aims: Poor sleep quality (SQ) is associated with increased cardiovascular mortality and morbidity. Additionally, asymmetric dimethylarginine (ADMA) is an independent predictor of cardiovascular mortality and morbidity. However, no sufficient data regarding the relationship between ADMA levels and SQ have been reported. The goal of the current study was to evaluate the association between SQ and ADMA levels in normotensive patients with type 2 diabetes mellitus. Methods: The study participants consisted of 78 normotensive type 2 diabetics. The SQ of all participants was assessed using the Pittsburgh Sleep Quality Index (PSQI). Patients with a global PSQI score > 5 were defined as "poor sleepers." Factors associated with poor SQ were analyzed using a multiple regression model. Serum ADMA levels were measured using high performance liquid chromatography. Results: The median ADMA levels of the poor sleepers were increased compared with patients defined as good sleepers (5.5 [4.2 to 6.6] vs. 4.4 [2.9 to 5.4], p < 0.01, respectively). However, the L-arginine/ADMA ratio was decreased in poor sleepers (p < 0.01). Global PSQI scores were positively correlated with ADMA levels (p < 0.01) and negatively correlated with the L-arginine/ADMA ratio (p = 0.02). ADMA levels were correlated with sleep latency (p < 0.01) and sleep efficiency (p = 0.01). Logistic regression analysis showed that ADMA levels (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.16 to 2.44; p = 0.01) and body mass index (OR, 1.15; 95% CI, 1.01 to 1.31; p = 0.04) were associated with poor SQ independently of glomerular filtration rate, sex, age, duration of diabetes, hemoglobin $A_{1c}$, total cholesterol, and systolic blood pressure. Conclusions: Self-reported SQ was independently associated with ADMA levels in normotensive patients with diabetes mellitus.

Background/Aims: We evaluated the trend in the rates of drug-resistant tuberculosis (TB) over time, as well as the difference in the drug-resistance pattern between pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) at a private referral center in South Korea. Methods: All patients with culture-confirmed TB from 2006 to 2013 were included. Results: In total, 1,745 patients were included: 1,431 (82.0%) were new cases, and 314 (18.0%) were cases treated previously; 1,610 (92.3%) were diagnosed with PTB, and 135 (7.7%) were diagnosed with EPTB. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB were detected in 5.8% and 2.0% of new cases and in 20.1% and 8.6% of previously treated cases, respectively. The MDR TB rate during the study period decreased remarkably, whereas the MDR and XDR TB rates decreased significantly in previously treated cases. No difference in the drug-resistance rate was detected between PTB and EPTB. Conclusions: The TB drug-resistance rate, particularly that of MDR TB, remained high at a private referral hospital, and the drug-resistance rate did not decrease significantly from 2006 to 2013. This finding underscores the need for a national survey regarding the prevalence of drug-resistant TB to obtain the most accurate and current drug-resistance status in South Korea, including the private sector.

Background/Aims: The diagnostic accuracy of thyroid dysfunctions is primarily affected by the validity of the reference interval for serum thyroid-stimulating hormone (TSH). Thus, the present study aimed to establish a reference interval for TSH using a normal Korean population. Methods: This study included 19,465 subjects who were recruited after undergoing routine health check-ups. Subjects with overt thyroid disease, a prior history of thyroid disease, or a family history of thyroid cancer were excluded from the present analyses. The reference range for serum TSH was evaluated in a normal Korean reference population which was defined according to criteria based on the guidelines of the National Academy of Clinical Biochemistry, ultrasound (US) findings, and smoking status. Sex and age were also taken into consideration when evaluating the distribution of serum TSH levels in different groups. Results: In the presence of positive anti-thyroid peroxidase antibodies or abnormal US findings, the central 95 percentile interval of the serum TSH levels was widened. Additionally, the distribution of serum TSH levels shifted toward lower values in the current smokers group. The reference interval for TSH obtained using a normal Korean reference population was 0.73 to 7.06 mIU/L. The serum TSH levels were higher in females than in males in all groups, and there were no age-dependent shifts. Conclusions: The present findings demonstrate that the serum TSH reference interval in a normal Korean reference population was higher than that in other countries. This result suggests that the upper and lower limits of the TSH reference interval, which was previously defined by studies from Western countries, should be raised for Korean populations.

Background/Aims: Neutrophil gelatinase-associated lipocalin (NGAL) is a wellknown biomarker of acute kidney injury. We evaluated the value of plasma NGAL (pNGAL) as an independent predictor of prognosis in immunoglobulin A nephropathy (IgAN). Methods: In total, 91 patients with biopsy-proven IgAN at a single center were evaluated. pNGAL was measured using a commercial enzyme-linked immunosorbent assay kit (R&D Systems). Adverse renal outcome was defined as chronic kidney disease (CKD) stage 3 or above at the last follow-up. Pearson correlation coefficient and Cox regression were used for analyses. Results: The mean age of all patients (male:female, 48:43) was 35 years (range, 18 to 77). pNGAL ranged between 21.68 and 446.40 ng/mL (median, 123.97) and showed a correlation with age (r = 0.332, p = 0.001), creatinine (r = 0.336, p = 0.001), estimated glomerular filtration rate (r = -0.397, p < 0.001), uric acid (r = 0.289, p = 0.006), and the protein-to-creatinine ratio (r = 0.288, p = 0.006). During a mean follow-up period of 37.6 months, 11 patients (12.1%) had CKD stage 3 or above. In a multivariate Cox regression model, hypertension (hazard ratio [HR], 8.779; 95% confidence interval [CI], 1.526 to 50.496; p = 0.015), proteinuria > 1 g/day (HR, 5.184; 95% CI, 1.124 to 23.921; p = 0.035), and pNGAL (HR, 1.012; 95% CI, 1.003 to 1.022; p = 0.013) were independent predictors associated with adverse renal outcome. Conclusions: pNGAL showed strong correlations with other clinical prognostic factors and was also an independent predictor of adverse renal outcome. We suggest pNGAL as a potential predictor for prognosis in IgAN, while further studies are needed to confirm the clinical value.

Background/Aims: Tubulointerstitial injury plays an important role in the progression of immunoglobulin A nephropathy (IgAN), and neutrophil gelatinase-associated lipocalin (NGAL) is among the most sensitive tubular biomarkers. We investigated whether serum or urine NGAL predicts prognosis in patients with IgAN. Methods: The present study enrolled patients with biopsy-proven IgAN from January 2005 to December 2010, whose serum and urine samples at the time of kidney biopsy were preserved by freezing. We retrospectively reviewed patient clinical data and followed patients until October 2012. Serum and urine NGAL levels were measured using an enzyme-linked immunosorbent assay kit. Renal progression was defined as an estimated glomerular filtration rate decline by > 50% or progression to end-stage renal disease. Results: There were 121 patients enrolled in this study. During the median follow-up period of 41.49 months, renal progression was found in nine patients (7.4%). Serum or urine NGAL alone could not predict renal progression; however, when serum and urine NGAL levels were combined, belonging to the high NGAL group independently predicted renal progression (hazard ratio [HR], 5.56; 95% confidence interval [CI], 1.42 to 21.73; p = 0.014), along with tubular damage graded according to the Oxford classification as $T_2$ (HR, 8.79; 95% CI, 2.01 to 38.51; p = 0.004). In addition, a Kaplan-Meier curve of renal survival showed significantly higher renal progression in patients in the high NGAL group (log rank, p = 0.004). Conclusions: In patients with IgAN, high serum and urine NGAL levels at the time of kidney biopsy predict renal progression.

Background/Aims: Several studies have demonstrated the effect of autologous hematopoietic stem cell transplantation (auto-HSCT) as a salvage treatment for patients with relapsed diffuse large B-cell lymphoma (DLBCL). However, the role of auto-HSCT as a frontline treatment has not been fully investigated in the rituximab era. We validated the age-adjusted International Prognostic Index (aaIPI) score for high-risk DLBCL patients and identified a possible role for frontline auto-HSCT. Methods: We recommended frontline auto-HSCT for high-risk DLBCL patients who satisfied the criteria of both a higher Ann-Arbor stage (III to IV) and an elevated lactate dehydrogenase (LDH) level at diagnosis with an aaIPI $score{\geq}2$. From 2006 to 2011, among the 150 DLBCL patients aged ${\leq}60$ years who were treated with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), 23 high-risk patients with a complete response (CR) were treated with auto-HSCT. For comparison, we selected 35 well-matched high-risk patients with CR who completed R-CHOP treatment alone. In addition, there were 81 low-risk patients and 11 refractory patients. Results: DLBCL patients with an aaIPI $score{\geq}2$ showed inferior overall survival (OS; p = 0.040) and progression-free survival (PFS; p = 0.007) compared to the aaIPI score 0 to 1. Between the two treatment arms among the high-risk DLBCL patients, the clinical parameters were not different. The high-risk group treated with frontline auto-HSCT showed similar OS (p = 0.392) and PFS (p = 0.670) to those in the low-risk group. Thus, frontline auto-HSCT showed superior PFS (p = 0.004), but only a trend towards favorable OS (p = 0.091) compared to R-CHOP alone. Conclusions: We identified the possible role of frontline auto-HSCT for high-risk DLBCL with a higher stage (III to IV) and elevated LDH level.

Background/Aims: Acute pyelonephritis (APN) is the most common cause of community-onset bacteremia in hospitalized elderly patients. The objectives of this study were to investigate the differences in the clinical and microbiological data of hospitalized elderly and non-elderly women with community-onset APN. Methods: Women with community-onset APN as a discharge diagnosis were identified from January 2004 to December 2013 using an electronic medical records system. We compared the clinical and microbiologic data in elderly and non-elderly women with community-onset APN due to Enterobacteriaceae. Results: Of the 1,134 women with community-onset APN caused by Enterobacteriaceae, 443 were elderly and 691 were non-elderly women. The elderly group had a lower frequency of upper and lower urinary tract symptoms/signs than the non-elderly. The incidence of bacteremia, extended-spectrum ${\beta}-lactamase$ (ESBL)-producing Enterobacteriaceae, patients with a C-reactive protein (CRP) level ${\geq}15mg/dL$, and patients with a leukocyte count ${\geq}15,000/mm^3$ in the blood, were significantly higher in the elderly group than in the non-elderly group. The proportion of patients requiring hospitalization for 10 days or more was significantly higher in the elderly group compared to the non-elderly group (51.5% vs. 26.2%, p < 0.001). The clinical cure rates at 4 to 14 days after the end of therapy were 98.3% (338/344) and 97.4% (519/533) in the elderly and non-elderly groups, respectively (p = 0.393). Conclusions: Elderly women with APN exhibit higher serum CRP levels, a higher frequency of bacteremia, a higher proportion of ESBL-producing uropathogens, and require a longer hospitalization than non-elderly women, although these patients may not complain of typical urinary symptoms.

Background/Aims: The aim of this study was to compare the sleep quality between rheumatoid arthritis (RA) patients and healthy controls; and to evaluate the relationship between RA disease activity and sleep quality in Korea. Methods: A total of 130 RA patients and 67 age- and sex-matched healthy controls were enrolled in a comparative study of sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Age, gender, concomitant medication, erythrocyte sedimentation rate, serum C-reactive protein, Beck Depression Inventory second edition (BDI-II), 28 joints disease activity score (DAS28), pain visual analog scale (VAS), and PSQI were analyzed as covariates. We also analyzed the sleep quality of RA patients according to the disease activity ($DAS28{\leq}3.2$, 3.2 < DAS28 < 5.1, and $DAS28{\geq}5.1$, respectively). Results: The total PSQI score and the frequency of poor sleep quality, were higher in the RA patients ($5.62{\pm}4.19$, 38.5%) than in the control subjects ($3.57{\pm}2.17$, 13.4%). The patients with poor sleep quality (PSQI > 5) were older and had a higher BDI-II and VAS score than the patients without sleep disturbance ($PSQI{\leq}5$). The score in subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, daytime dysfunction, total PSQI, and frequency of poor sleep quality were increased when RA activity was high. Conclusions: Sleep disturbance was observed in RA patients (38.5%), and high RA disease activity was associated with poor sleep quality in Korea.

Background/Aims: The course of ankylosing spondylitis (AS) is rather variable, and the factors that predict radiographic progression remain largely obscure. In this study, we tried to determine the clinical factors and laboratory measures that are useful in predicting the radiographic progression of patients with AS. Methods: In 64 consecutive patients with AS, we collected radiographic and laboratory data over 3 years. Radiographic data included images of the sacroiliac (SI) and hip joints and laboratory data included areas under the curve (AUC) of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), alkaline phosphatase (ALP), and hemoglobin (Hb). We investigated associations among changes in radiographic scores, initial clinical manifestations and laboratory measurements. Results: Changes in scores for the SI joint and lumbar spine did not correlate with AUC for ESR, CRP, or ALP. AUC for Hb did not significantly correlate with radiographic progression in any joint. Patients with hip arthritis at the initial visit showed significantly higher radiographic score changes after 3 years in the SI and hip joint compared to those without hip arthritis. Patients who had shoulder arthritis as the initial manifestation had significantly increased AUCs for ESR and CRP compared to those without shoulder arthritis. However, at 3 years, the change of the lumbar spine score was significantly higher in patients without shoulder arthritis. Conclusions: These results indicate that hip arthritis at presentation is a useful clinical marker for predicting the structural damage to the SI and hip joint, and suggest that initial shoulder arthritis correlates with slower radiographic progression of the lumbar spine.