In 2017, the Korean Diabetes Association (KDA) published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). The KDA regularly updates its Clinical Practice Guidelines, but since the last update in 2015, many results from clinical trials have been introduced, and domestic data from studies performed in Korean patients with T2DM have been published. Recently, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations. Additionally, new data from clinical trials using dipeptidyl peptidase 4 inhibitors and thiazolidinediones in Korean patients with T2DM were added. Following a systematic review and assessment of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the use of antihyperglycemic agents and revised the treatment algorithm for Korean adult patients with T2DM.

In order to improve the quality of life and to prevent chronic complications related to diabetes mellitus, intensive lifestyle modification and proper medication are needed from the early stage of diagnosis of type 2 diabetes mellitus (T2DM). When using the first medication for diabetic patients, the appropriate treatment should be selected considering the clinical characteristics of the patient, efficacy of the drug, side effects, and cost. In general, the use of metformin as the first treatment for oral hypoglycemic monotherapy is recommended because of its excellent blood glucose-lowering effect, relatively low side effects, long-term proven safety, low risk of hypoglycemia, and low weight gain. If metformin is difficult to use as a first-line treatment, other appropriate medications should be selected in view of the clinical situation. If the goal of achieving glycemic control is not achieved by monotherapy, a combination therapy with different mechanisms of action should be initiated promptly.

The Korean Diabetes Association (KDA) has regularly updated its Clinical Practice Guidelines. In 2017, the KDA published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). Growing evidence from new multinational clinical trials using novel and traditional insulin analogues has also been accumulated. Following global trends, many results of clinical trials, especially concerning the clinical efficacy and safety of insulin therapy, have been published about Korean patients with T2DM. After a systematic search of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the initiation, choice, and intensification of insulin and created an insulin treatment algorithm for the first time to guide physicians caring for adult Korean patients with T2DM.

The Korean Diabetes Association (KDA) recently updated the Clinical Practice Guidelines on antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus (T2DM). In combination therapy of oral hypoglycemic agents (OHAs), general recommendations were not changed from those of the 2015 KDA guidelines. The Committee on Clinical Practice Guidelines of the KDA has extensively reviewed and discussed the results of meta-analyses and systematic reviews of effectiveness and safety of OHAs and many clinical trials on Korean patients with T2DM for the update of guidelines. All OHAs were effective when added to metformin or metformin and sulfonylurea, although the effects of each agent on body weight and hypoglycemia were different. Therefore, selection of a second agent as a metformin add-on therapy or third agent as a metformin and sulfonylurea add-on therapy should be based on the patient's clinical characteristics and the efficacy, side effects, mechanism of action, risk of hypoglycemia, effect on body weight, patient preference, and combined comorbidity. In this review, we address the results of meta-analyses and systematic reviews, comparing the effectiveness and safety among OHAs. It will help to choose the appropriate drug for an individual patient with T2DM.

Although debate on the concept of fibromyalgia (FM) has been vigorous ever since the classification criteria were first published, FM is now better understood and has become recognized as a disorder. Recently, FM has come to be considered a major health problem, affecting 1% to 5% of the general population. As familial aggregations have been observed among some FM patients, genetic research on FM is logical. In fact, genome-wide association studies and linkage analysis, and studies on candidate genes, have uncovered associations between certain genetic factors and FM. Genetic susceptibility is now considered to influence the etiology of FM. At the same time, novel genetic techniques, such as microRNA analysis, have been used in attempts to improve our understanding of the genetic predisposition to FM. In this article, we review recent advances in, and continuing challenges to, the identification of genes contributing to the development of, and symptom severity in, FM.

Background/Aims: The aim of this study was to compare the effects of erythromycin infusion and gastric lavage in order to improve the quality of visualization during emergency upper endoscopy. Methods: We performed a prospective randomized pilot study. Patients presented with hematemesis or melena within 12 hours and were randomly assigned to the erythromycin group (intravenous infusion of erythromycin), gastric lavage group (nasogastric tube placement with gastric lavage), or erythromycin + gastric lavage group (both erythromycin infusion and gastric lavage). The primary outcome was satisfactory visualization. Secondary outcomes included identification of a bleeding source, the success rate of hemostasis, duration of endoscopy, complications related to erythromycin infusion or gastric lavage, number of transfused blood units, rebleeding rate, and bleeding-related mortality. Results: A total of 43 patients were randomly assigned: 14 patients in the erythromycin group; 15 patients in the gastric lavage group; and 14 patients in the erythromycin + gastric lavage group. Overall satisfactory visualization was achieved in 81% of patients: 92.8% in the erythromycin group; 60.0% in the gastric lavage group; and 92.9% in the erythromycin + gastric lavage group, respectively (p = 0.055). The identification of a bleeding source was possible in all cases. The success rate of hemostasis, duration of endoscopy, and number of transfused blood units did not significantly differ between groups. There were no complications. Rebleeding occurred in three patients (7.0%). Bleeding-related mortality was not reported. Conclusions: Intravenous erythromycin infusion prior to emergency endoscopy for acute nonvariceal upper gastrointestinal bleeding seems to provide satisfactory endoscopic visualization.

Background/Aims: Combined treatment of pegylated $interferon-{\alpha}$ (PEG-IFN) and ribavirin (RBV) has long been accepted as the standard treatment for chronic hepatitis C virus (HCV) infection. Many predictive factors for treatment response have been identified. The aim of this study was to evaluate the efficacy and safety of combined PEG-IFN plus RBV and to examine the value of serum uric acid as a predictive factor in the treatment of chronic hepatitis C. Methods: A total of 74 patients chronically infected with HCV were enrolled between December 2004 and June 2009. Patients received subcutaneous PEG-IFN (${\alpha}-2a$: $180{\mu}g$ once a week) in combination with RBV (1,000 to 1,200 mg daily depending on body weight). We evaluated treatment responses represented by early virologic response (EVR), end-of-treatment response (ETR), sustained virologic response (SVR), and relapse, as well as diverse adverse events. Various viral and host features were also assessed to clarify factors associated with treatment response. Results: During treatment, EVR was achieved in 26 patients (26/33, 78.8%) with HCV genotype 1. ETR and SVR were achieved in 59 (77.6%) and 56 patients (73.6%), respectively, across all genotypes. Genotype 2/3, lower HCV RNA, and lower uric acid were associated with higher SVR. Conclusions: The treatment response to combination therapy with PEG-IFN plus RBV was effective, especially in genotype 2/3. Uric acid might be useful as a predictive factor for response to therapy for chronic hepatitis.

Background/Aims: Although lipoprotein lipase (LPL) gene Pvu II polymorphism has been associated with an increased risk of hypertriglyceridemia (HT), there is no clear consensus within the scientific community. Methods: A meta-analysis of 1,640 subjects from six individual studies was conducted to better elucidate the potential relationship between the LPL gene Pvu II polymorphism and HT within the Chinese population. Pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were evaluated by using fixed effect models. Results: Our analysis indicated a significant association between LPL gene Pvu II polymorphism and HT within the Chinese population under allelic (OR, 1.550; 95% CI, 1.320 to 1.830; $p=1.158{\times}10^{-7}$), recessive (OR, 0.540; 95% CI, 0.390 to 0.750; p = 0.0002), dominant (OR, 1.889; 95% CI, 1.501 to 2.377; $p=5.960{\times}10^{-8}$), homozygous (OR, 2.167; 95% CI, 1.531 to 3.067; $p=1.242{\times}10^{-5}$), heterozygous (OR, 1.810; 95% CI, 1.419 to 2.309; $p=1.842{\times}10^{-6}$), and additive genetic models (OR, 1.553; 95% CI, 1.320 to 1.828; $p=1.158{\times}10^{-7}$). Conclusions: Because LPL gene Pvu II restriction fragment length polymorphism polymorphism was associated with an elevated risk of HT, the P+ allele carriers of the LPL gene might be predisposed to HT.

Background/Aims: Fimasartan is an angiotensin type 1 receptor blocker (ARB) which has comparable efficacy and tolerability with other ARBs. The aim of this study was to evaluate 24-hour blood pressure (BP) lowering efficacy and the tolerability of the low dose fimasartan compared with valsartan in patients with mild to moderate hypertension. Methods: This study was a phase II, prospective, multicenter, randomized, double-blind, parallel-grouped trial. A total of 75 hypertensive patients, whose mean ambulatory BP monitoring values were ${\geq}135/85mmHg$, were randomized to either fimasartan 30 mg or valsartan 80 mg daily. The primary efficacy endpoint was the change in the mean 24-hour systolic BP (SBP) values from the baseline and at the week 8. Secondary endpoints included the change in the mean 24-hour diastolic BP values, the daytime and the nighttime mean BP values at week 8, the trough-to-peak (T/P) ratio and the smoothness index. Results: At week 8, the mean 24-hour SBP values significantly decreased in both groups; $-10.5{\pm}11.9mmHg$ (p < 0.0001) in the fimasartan group and $-5.5{\pm}11.6mmHg$ (p = 0.0307) in the valsartan group. The difference between two groups was $4.3{\pm}2.9mmHg$ but there was no statistical significance (p = 0.1392). The global T/P ratio in the fimasartan 30 mg groups were 0.48 and 0.40 in the valsartan 80 mg group, respectively (p = 0.3411). The most frequent adverse events (AEs) were acute pharyngitis and there were no cases of severe AEs. Conclusions: In mild-to-moderate hypertensive patients, low dose (30 mg) fimasartan showed comparable 24-hour BP lowering efficacy compared with valsartan (80 mg). There was no difference in tolerability between two groups.

Background/Aims: Despite increasing interest in pulmonary thromboembolism (PTE), data on recent trends in PTE incidence are limited. This study evaluated the recent incidence rate of PTE. Methods: We performed a retrospective chart review of patients with PTE admitted to Chung-Ang University Hospital during the 10-year period from 2006 to 2015. Age-standardized incidence and mortality rates were calculated by the direct method per 100,000 populations. To analyze the trend of risk factor, we also calculated the proportions of cancer, major operation, and recent major fracture over that time. Results: Total crude incidence rate of PTE per 100,000 was 229.36 and the age-sex adjusted standardized incidence rate was 151.28 (95% confidence interval [CI], 127.88 to 177.10). The incidence rate have been significantly increased 1.083 times annually from 2006 (105.96 per 100,000) to 2015 (320.02 per 100,000) (95% CI, 1.049 to 1.118; p < 0.001). These incidences also increased annually in age group of 35 to 54, 55 to 74, and ${\geq}$ 75 years, and in both males (odds ratio [OR], 1.071; 95% CI, 1.019 to 1.127; p = 0.007) and females (OR, 1.091; 95% CI, 1.047 to 1.136; p < 0.001). Cancer accounted for most of the increase from 20.0% at 2006 to 2007 to 42.8% at 2014 to 2015 (OR, 1.154; 95% CI, 1.074 to 1.240; p < 0.001), while the proportions of recent fracture and major operation remained constant. Conclusions: The incidence of pulmonary embolism has gradually increased over the 10 years. The increase of PTE incidence was mainly due to increased proportion of cancer patients.

Background/Aims: The p22phox C242T gene polymorphism (rs4673) may be linked to an increased susceptibility for overt diabetic nephropathy (ODN), but the study results are still inconclusive. Methods: To explore the relationship between p22phox C242T gene polymorphism and ODN, the current meta-analysis of 707 ODN patients and 745 controls from five individual studies was conducted. The pooled odds ratio (OR) and its corresponding 95% confidence interval (CI) were evaluated by either a random or fixed effect model. Results: In our meta-analysis, a significant relationship between the p22phox C242T gene polymorphism and ODN was found under allelic (OR, 2.760; 95% CI, 1.400 to 5.450; p = 0.004), recessive (OR, 5.080; 95% CI, 1.020 to 25.430; p = 0.05), dominant (OR, 1.700; 95% CI, 1.167 to 2.477; p = 0.006), homozygous (OR, 3.900; 95% CI, 1.022 to 14.889; p = 0.046), heterozygous (OR, 1.523; 95% CI, 1.167 to 1.986; p = 0.002), and additive genetic models (OR, 2.019; 95% CI, 1.232 to 3.309; p = 0.005). Conclusions: A positive correlation between p22phox C242T gene polymorphism and ODN risk was found. The T allele carriers of p22phox C242T gene polymorphism might be predisposed to ODN.

Background/Aims: Recent findings have demonstrated the occurrence of neutrophil transendothelial migration in the reverse direction (reverse TEM) and that endothelial junctional adhesion molecule C (JAM-C) is a negative regulator of reverse TEM. In this study, we tested the effects of a JAM-C blocking antibody on the resolution of kidney injuries and inflammation in a mouse model of cisplatin-induced acute kidney injury (AKI). Methods: Cisplatin was administered via intraperitoneal injection. A JAM-C blocking antibody or a control immunoglobulin G was administered intraperitoneal at 1.5 mg/kg, with the injection being delayed until day 4 following cisplatin administration to restrict the effect of antibodies on recovery. Results: After cisplatin injection, serum creatinine and histologic injuries peaked on day 4. Treatment with a JAM-C blocking antibody on days 4 and 5 promoted the functional and histologic recovery of cisplatin-induced AKI on days 5 and 6. Facilitating recovery with a JAM-C blocking antibody correlated with significantly increased circulating intercellular adhesion molecule $_1{^+}$ Tamm-Horsfall $protein^+$ neutrophils and significantly decreased renal neutrophil infiltration, indicating that facilitating reverse the TEM of neutrophils from the kidney to the peripheral circulation partially mediated the resolution of inflammation and recovery. Conclusions: These results demonstrated that reverse TEM is involved in the resolution of neutrophilic inflammation in cisplatin-induced AKI and that JAM-C is an important regulator of this process.

Background/Aims: Proteinuria is associated with hypertension and preeclampsia in pregnancy. However, the impact of random urine proteinuria on fetal and maternal outcomes has not been established. We investigated the influence of random urine proteinuria on the clinical outcomes of pregnancy. Methods: From January 2008 to December 2010, 2,822 patients were retrospectively studied. A total of 536 pregnant women with proteinuria in random urine and matched controls without proteinuria via propensity score matching were analyzed. Proteinuria was checked by the dipstick method. Results: The patients' mean age was $33.0{\pm}4.7years$, and the mean gestational age was $235.6{\pm}50.6days$ on admission. The prevalence of hypertension and chronic kidney disease was 2.4% (n = 67) and 1.0% (n = 29), respectively. Women with random urine proteinuria showed higher blood urea nitrogen levels and a higher incidence of hematuria. These women also had a higher incidence of preeclampsia, preterm labor, premature rupture of membranes, and intrauterine growth restriction. Proteinuria was strongly correlated with preeclampsia in both propensity score matching (p < 0.001, r = 0.783) and unmatched whole samples (p < 0.001, r = 0.851). Conclusions: These findings suggest that random urine proteinuria is associated with preeclampsia, preterm labor, premature rupture of membrane, and intrauterine growth restriction.

Background/Aims: Cancer-induced bone pain (CIBP) is one of the most common pains in patients with advanced neoplasms. Because of treatment-associated side effects, more than half of cancer patients are reported to have inadequate and undermanaged pain control. New mechanism-based therapies must be developed to reduce cancer pain. Quetiapine is a commonly used atypical antipsychotic drug. We report a study of the potential analgesic effects of quetiapine in a mouse model of CIBP and examine the mechanism of bone pain by analyzing the expression of various nociceptors. Methods: Fifteen male C3H/HeN mice were arbitrarily divided into five groups: control and, CIBP with no treatment, quetiapine treatment, opioid treatment, and melatonin treatment. The mice were tested for mechanical hyperalgesia by determining the nociceptive hind paw withdrawal pressure threshold. Tissues from tibia were removed and subjected to quantitative and qualitative evaluations of transient receptor potential vanilloid 1 (TRPV1), TRPV4, acid-sensing ion channel 1 (ASIC1), ASIC2, and ASIC3 expression. Results: Paw withdrawal pressure threshold was improved in the quetiapine treatment group compared with the CIBP group. Expression of TRPV1, TRPV4, ASIC1, ASIC2, and ASIC3 in the CIBP with quetiapine treatment group was significantly lower than that in the CIBP group. Conclusions: Our results suggest an analgesic effect of quetiapine in the CIBP animal model and implicate TRPV and ASICs as potential targets for cancer pain management.

Background/Aims: Brucellosis patients present various non-specific clinical symptoms, such as fever, fatigue, sweating, joint pain, arthritis, myalgia, and headache. Based on the nonspecifity of its clinical signs and symtoms, we decided to evaluate whether mean platelet volume (MPV), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) will contribute to the diagnosis. Methods: In this retrospective study, we reviewed hospital-records of 60 children with a confirmed diagnosis of brucellosis in Kayseri between January 2013 and January 2016, and compared the hematological parameters; white blood cell (WBC) count, hemoglobin (Hb), neutrophil count, lymphocyte count, platelet count, MPV, NLR, and PLR with 55 healthy age and gender matched children. Also, the well known inflammation markers; erytrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were compared between the patient and control group. Results: We found significant difference among the Hb, platelet count, MPV and NLR values between the patient and control group (p < 0.05). There was no difference between WBC, neutrophil count, lymphocyte count and PLR between the patient and control group (p > 0.05). When the patients were divided into groups as arthritis positive and arthritis negative and compared to the control group; we found that the NLR is more significant in between the arthritis positive and control group (p = 0.013). Also, we found significant difference among the ESR and CRP values between the patient and control group (p < 0.001). Conclusions: The results of this study indicates that MPV and NLR values can be used as markers of inflammation in childhood brucellosis. Also, NLR is more valuable in children with brucella arthritis.

Background/Aims: $^{18}F-fluorodeoxyglucose$ positron emission tomography/computed tomography ($^{18}F-FDG$ PET/CT) has been suggested as a reliable imaging technique for monitoring of disease activity in patients with adult-onset Still's disease (AOSD). Therefore, we investigated the clinical significance of $^{18}F-FDG$ PET/CT in Korean AOSD patients. Methods: Thirteen AOSD patients were included in the study. The PET/CT images were evaluated with visual and semiquantitative method using standardized uptake values (SUVs). Results: The presence of increased $^{18}F-FDG$ uptake was noted in 90% of clinically active AOSD patients. $^{18}F-FDG$ uptake was located in the lymph node, spleen, and bone marrow. Visual grade and SUV intensity of lymph node was significantly correlated with the systemic score of AOSD. Visual grade of spleen was significantly correlated with the systemic score, erythrocyte sedimentation rate (ESR), and ferritin. Additionally, visual grade and SUV intensity of bone marrow was significantly correlated with the systemic score, ESR, leukocyte, and neutrophil. Conclusions: Visual grade and SUV intensity of lymph node, spleen, and bone marrow on $^{18}F-FDG$ PET/CT scan showed significant correlations with known disease activity markers. The data suggest that $^{18}F-FDG$ PET/CT scan may be a useful imaging technique for evaluation of disease activity in AOSD patients.

Background/Aims: Nontuberculous mycobacteria (NTM) infection has been increasing worldwide in both general population and immunocompromised patients, which has also been reported in rheumatoid arthritis (RA) patients. This study aimed to identify the incidence and clinical characteristics of NTM infection in RA patients living in tuberculosis (TB) infection endemic area. Methods: We performed a retrospective analysis of NTM infection cases in our RA registry at a tertiary referral center from January 1995 to December 2013. The clinical features of them were compared to those of 52 TB infection patients from same registry. Results: Among 1,397 patients with RA, NTM infection was newly developed in 26 patients and the incidence of NTM infection was 164.8 per 100,000 patient-years. The Mycobacterium avium complex was the most frequent isolate (76.9%). None of the NTM infections had extrapulmonary involvement, which was rather common in TB infection (26.9%). Patients with NTM infection were older, received higher cumulative steroid doses, and had higher rates of past TB infection history and concomitant interstitial lung disease (ILD) than cases with TB infection. Conclusions: In South Korea, NTM infection is not rare in RA patients, and infection rates are growing. Physicians should be cautious about NTM infection in patients with a history of TB infection or concomitant ILD, even living in TB endemic area.