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Hee-Won Moon, , Mina Hur,
The Korean journal of internal medicine, Volume 33, pp 893-901;

In countries with a higher risk of gastric atrophic gastritis, noninvasive tests are helpful for a more reliable diagnosis of Helicobacter pylori infection. The aim of this study was to evaluate the characteristics of seropositive subjects according to their stool H. pylori antigen test, serum pepsinogen (PG) assay, and endoscopic findings. Consecutive subjects who visited Konkuk University Medical Center for upper gastrointestinal endoscopy for a regular check-up were included in a prospective setting if the serum anti-H. pylori immunoglobulin G assay was positive. A H. pylori antigen stool test was measured using a stool H. pylori antigen enzyme-linked immunosorbent assay kit on the same day as a serum PG assay and endoscopy. Of 318 seropositive subjects, 256 (80.5%) showed positive stool test findings. Subjects with a negative stool test result showed lower serum PG I (p < 0.001) and PG II (p < 0.001) levels and higher PG I/II ratio (p < 0.001) than those with a positive stool test. Chronic atrophic gastritis was more common in the positive stool test group than the negative stool test group on endoscopic finding (p = 0.009). A higher serum PG I level (p = 0.001) and a lower serum PG I/II ratio (p = 0.001) were independent risk factors for the presence of H. pylori antigen in stool. A high serum PG level denotes an ongoing current H. pylori infection with positive stool H. pylori antigen test findings. Seropositive subjects with increased gastric secreting ability tend to have H. pylori in their fecal material as reflected by a positive stool H. pylori antigen test finding.
Sang Gon Lee, Hee-Jung Chung, Jeong Bae Park, Hyosoon Park,
The Korean journal of internal medicine, Volume 33, pp 1119-1128;

We found that more comparable results can be produced by laboratory data harmonization using commutable samples. Therefore, harmonization efforts should be undertaken in multicenter trials for accurate data analysis (CRIS number; KCT0001235).
Dong-Jin Park, Shin-Seok Lee
The Korean journal of internal medicine, Volume 32, pp 984-995;

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.
Seung-Hyun Ko, Kyu-Yeon Hur, , Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, , Kyung Mook Choi, Jin Hwa Kim, et al.
The Korean journal of internal medicine, Volume 32, pp 947-958;

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.
Byung-Wan Lee, Jin Hwa Kim, Seung-Hyun Ko, Kyu Yeon Hur, Nan-Hee Kim, , , Min Kyong Moon, Seok-O Park, Kyung Mook Choi, et al.
The Korean journal of internal medicine, Volume 32, pp 967-973;

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.
, , Seung-Hyun Ko, Kyu Yeon Hur, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Kyung Mook Choi, Jin Hwa Kim, et al.
The Korean journal of internal medicine, Volume 32, pp 959-966;

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.
Jung-Yeon Lim, Keon-Il Im, Yunejin Song, Nayoun Kim, Young-Sun Nam, Young-Woo Jeon, Seok-Goo Cho
The Korean journal of internal medicine, Volume 33, pp 980-989;

Adoptive therapy with regulatory T (Treg) cells to prevent graft-versus-host disease (GVHD) would benefit from a strategy to improve homing to the sites of inflammation following hematopoietic stem cell transplantation (HSCT). Although donor-derived Treg cells have mainly been used in these models, third-party-derived Treg cells are a promising alternative for cell-based immunotherapy, as they can be screened for pathogens and cell activity, and banked for GVHD prevention. In this study, we explored major histocompatibility complex (MHC) disparities between Treg cells and conventional T cells in HSCT to evaluate the impact of these different cell populations on the prevention of acute GVHD, as well as survival after allogeneic transplantation.To induce acute GVHD, lethally irradiated BALB/c (H-2d) mice were transplanted with 5 × 105 T cell-depleted bone marrow cells and 5 × 105 CD4+CD25- splenic T cells from C57BL/6 (H-2b) mice. Recipients were injected with 5 × 105 cultured donor-, host-, or third-party-derived CD4+CD25+CD62L+ Treg cells (bone marrow transplantation + day 1).Systemic infusion of three groups of Treg cell improved clinicopathological manifestations and survival in an acute GVHD model. Although donor-derived Treg cells were immunologically the most effective, the third-party-derived Treg cell therapy group displayed equal regulation of expansion of CD4+CD25+- Foxp3+ Treg cells and suppressive CD4+IL-17+ T-helper (Th17) cells in ex vivo assays compared with the donor- and host-derived groups.Our findings demonstrate that the use of third-party Treg cells is a viable alternative to donor-derived Treg cellular therapy in clinical settings, in which human leukocyte antigen-matched donors are not always readily available.
Seon Ha Baek, Sejoong Kim, Ki Young Na, Suhnggwon Kim, Ho Jun Chin
The Korean journal of internal medicine, Volume 33, pp 970-979;

Predialysis hyponatremia has been recently reported to be associated with mortality in incident hemodialysis patients. However, whether hyponatremia is associated with unfavorable outcomes in elderly patients remains unknown. We hypothesized that nephrology referral inf luences hyponatremia, and aimed to define how nephrology referral affects the association between hyponatremia and mortality in the elderly. We retrospectively assessed mortality in 599 incident hemodialysis patients aged ≥ 70 at a tertiary university hospital, between 2000 and 2010. We analyzed 90-day and 1-year all-cause mortality (ACM) in relation to predialysis serum sodium (sNa). We divided the patients into two groups according to predialysis glucose-corrected sNa: hyponatremia (< 135 mmol/L) and normonatremia (135 to 145 mmol/L). Low estimated glomerular filtration rate, high phosphorus, low albumin, nonpreparation of arteriovenous fistula or graft, and late referral were associated with a low sNa in the elderly. Among 599 patients, 106 and 174 patients died at the 90-day and 1-year follow-ups, respectively. Each 10-mmol/L increase in predialysis sNa tended to be associated with lower 90-day and 1-year ACM. When patients were stratified by nephrology referral, hyponatremia was associated with increased mortality in early referral group (90-day ACM: hazard ratio [HR] = 2.335, p = 0.041; 1-year ACM: HR = 1.790, p = 0.024). However, hyponatremia was not associated with mortality in late referral group. Predialysis hyponatremia at hemodialysis initiation is associated with late referra
Jung-Wan Yoo, Seung Jun Lee, Jong Deog Lee,
The Korean journal of internal medicine, Volume 33, pp 331-339;

Both diaphragmatic excursion and change in muscle thickening are measured using ultrasonography (US) to assess diaphragm function and mechanical ventilation weaning outcomes. However, which parameter can better predict successful extubation remains to be determined. The aim of this study was to compare the clinical utility of these two diaphragmatic parameters to predict extubation success.This study included patients subjected to extubation trial in the medical or surgical intensive care unit of a university-affiliated hospital from May 2015 through February 2016. Diaphragm excursion and percent of thickening change (Δtdi%) were measured using US within 24 hours before extubation.Sixty patients were included, and 78.3% (47/60) of these patients were successfully extubated, whereas 21.7% (13/60) were not. The median degree of excursion was greater in patients with extubation success than in those with extubation failure (1.65 cm vs. 0.8 cm, p < 0.001). Patients with extubation success had a greater Δtdi% than those with extubation failure (42.1% vs. 22.5%, p = 0.03). The areas under the receiver operating curve for excursion and Δtdi% were 0.836 (95% confidence interval [CI], 0.717 to 0.919) and 0.698 (95% CI, 0.566 to 0.810), respectively (p = 0.017).Diaphragm excursion seems more accurate than a change in the diaphragm thickness to predict extubation success.
Ji Soo Song, Hee Chul Yu, Woo Sung Moon
The Korean journal of internal medicine, Volume 33, pp 645-646;

Hong Ki Min, Youn Soo Lee, Suk-Woo Yang, Jennifer Lee, Seung-Ki Kwok, Ji Hyeon Ju, , Sung-Hwan Park
The Korean journal of internal medicine, Volume 34, pp 220-226;

This study investigated the clinical and pathological features of immunoglobulin G4 (IgG4)-related ophthalmic disease. To clarify the features, we compared IgG4-related ophthalmic disease and orbital inflammatory pseudotumor. We retrospectively reviewed the medical records of 103 patients who were initially diagnosed with orbital inflammatory pseudotumor, and identified 16 cases in which the diagnosis was based on surgical biopsy and for which data in medical records were sufficient for analysis. Immunohistochemical staining of pathological specimens for IgG and IgG4 was performed. Finally, six of IgG4-related ophthalmic disease patient and 10 of orbital inf lammatory pseudotumor patient were analyzed. The IgG4-related ophthalmic disease group had more IgG4-positive plasma cells and a higher IgG4/IgG plasma cell ratio than the orbital inflammatory pseudotumor group. Collagenous fibrosis and lacrimal gland involvement were significantly more frequent in the IgG4-related ophthalmic disease group. Dense lymphocyte infiltration, obliterative phlebitis, and bilateral lesions were more frequent in IgG4-related ophthalmic disease, but the differences were not significant. The recurrence-free period was shorter in the IgG4-related ophthalmic disease group (p = 0.035). The location of the lesion (lacrimal gland), count and ratio of IgG4-positive plasma cells, and collagenous fibrosis aid the diagnosis of IgG4-related ophthalmic disease in patients with idiopathic orbital mass-like lesions. In addition, maintenance therapy should be considered in patients with IgG4-related ophthalmic disease to prevent recurrence.
Hyung Joon Joo, Ji-Young Park, Soon Jun Hong, Kyoung-Ah Kim, Seung Hoon Lee, Jae-Young Cho, Jae Hyoung Park, Cheol Woong Yu, Do-Sun Lim
The Korean journal of internal medicine, Volume 33, pp 522-531;

Although epigallocatechin-3-gallate (EGCG), which is found in high contents in the dried leaves of green tea, has been reported to have an anti-platelet effect, synergistic effects of EGCG in addition to current anti-platelet medications remains to be elucidated.Blood samples were obtained from 40 participants who took aspirin (ASA, n = 10), clopidogrel (CPD, n = 10), ticagrelor (TCG, n = 10) and no anti-platelet medication (Control, n = 10). Ex vivo platelet aggregation and adhesion under various stimulators were analyzed by multiple electrode aggregometry (MEA) and Impact-R systems. PAC-1 and P-selectin expressions in human platelets were analyzed by flow cytometry.In MEA analysis, adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP)-induced platelet aggregations were lower in the CPD and the TCG groups; arachidonic acid (AA)-induced platelet aggregation was lower in the ASA group, whereas collagen (COL)-induced platelet aggregations were comparable among four groups. EGCG significantly reduced ADP- and COL-induced platelet aggregation in dose-dependent manner (ADP, p = 0.04; COL, p < 0.01). There were no additional suppressions of platelet aggregation stimulated by AA in the ASA group, and by ADP in the CPD and TCG groups. Moreover, EGCG suppressed shear stress-induced platelet adhesion on Impact-R, and had no effect on P-selectin and PAC-1 expressions.Ex vivo treatment of EGCG inhibited platelet adhesion and aggregation without changes in P-selectin and PAC-1 expression. There was no additional suppressions in platelet aggregation stimulated by AA in the ASA group and ADP in the CPD and TCG groups.
Natalia Buda, Anna Wszołek, Maciej Śledziński, Anton Żawrocki, Krzysztof Sworczak
The Korean journal of internal medicine, Volume 33, pp 1032-1033;

Hae-Young Lee, Cheol-Ho Kim, Jae-Kwan Song, Shung Chull Chae, , Ng-Soo Kim,
The Korean journal of internal medicine, Volume 32, pp 1025-1036;

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. 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 ≥ 135/85 mmHg, 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. At week 8, the mean 24-hour SBP values significantly decreased in both groups; –10.5 ± 11.9 mmHg (p < 0.0001) in the fimasartan group and –5.5 ± 11.6 mmHg (p = 0.0307) in the valsartan group. The difference between two groups was 4.3 ± 2.9 mmHg 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. 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.
Hyukjin Park, Young Joon Hong, Young Keun Ahn, , Jeong Gwan Cho,
The Korean journal of internal medicine, Volume 32, pp 1101-1103;

Jeong Eun Lee, Shinwon Lee, Sang Heon Song, Ihm Soo Kwak, Sun Hee Lee
The Korean journal of internal medicine, Volume 34, pp 409-417;

Little is known about tenofovir disoproxil fumarate (TDF)-induced nephrotoxicity in human immunodeficiency virus (HIV)-infected patients in Korea. The objective of this study was to evaluate the incidence and risk factors of TDF-associated nephrotoxicity among HIV-infected patients in Korea. A single-center retrospective cohort study was conducted on HIV-infected patients in Korea. We included patients who had started TDF or abacavir (ABC)-based antiretroviral therapy (ART) between October 2006 and December 2014. Estimated glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease-Epidemiology Collaboration equation. Renal dysfunction was defined as > 25% decrease of baseline eGFR. A propensity matched case-control study was conducted to compare renal dysfunction rates between the two groups. The risk factors of nephrotoxicity were analyzed by Cox regression analysis. A total of 210 HIV-infected patients were included in the study, of which, 108 were TDF-based ART group and 102 were ABC-based ART group. Renal dysfunction occurred in 16 patients (14.8%) in the TDF group and 11 (10.8%) in the ABC group. Incidence of renal dysfunction of TDF and ABC group was 9.66 per 100 person-years (PYs) and 5.14 per 100 PYs, respectively (p = 0.176). In propensity-score-matched analysis, renal dysfunction rates were TDF 13.3% versus ABC 13.3% (p > 0.999). In multivariable analysis, Centers for Disease Control and Prevention clinical category C was a significant risk factor for renal dysfunction. Approximately, 13% of HIV-infected patients treated with TDF had renal dysfunction. Advanced stage of HIV infection was a significant risk factor for renal dysfunction.
Ji Hun Kim, Min Kyung Chung, Jin Young Kang, Jung Hee Koh, Jennifer Lee, Seung-Ki Kwok, Ji Hyeon Ju, Sung-Hwan Park
The Korean journal of internal medicine, Volume 34, pp 202-209;

Gout is associated with metabolic disorders that are important risk factors for cardiovascular disease and erectile dysfunction (ED). We aimed to identify independent predictors of ED in patients with gout. From August 2014 to August 2015, male outpatients who were being treated for gout in our rheumatology clinic and healthy males without any history of inflammatory disease (control group) were studied. ED was assessed in participants using the five-item version of the International Index of Erectile Function questionnaire. Insulin resistance (IR) was estimated using the homeostatic model assessment (HOMA-IR). Logistic regression analysis was performed to determine the effect of variables on ED risk in all of the study subjects and in patients with gout. We analyzed 80 patients with gout and 70 healthy controls. The median age of patients with gout was 52 years and median disease duration was 120 months. Gout patients were more likely to have ED than controls (55.3% vs. 41.4%, p < 0.047). After adjustment for confounding factors, only HOMA-IR was significantly associated with ED (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.05 to 3.15). Gout patients with ED were more likely to be older (p < 0.001), have higher HOMA-IR (p = 0.048), and have lower glomerular filtration rate (p = 0.038) than those without ED. Multivariate logistic regression analysis showed that HOMA-IR was an independent predictor for ED (OR, 1.62; 95% CI, 1.03 to 2.82) in gout patients. IR is an independent predictor of ED in patients with gout.
Ye An Kim, Hye Sook Min, Sun Wook Cho, Young Joo Park
The Korean journal of internal medicine, Volume 32, pp 1121-1122;

Jung Sun Park, Hoon In Choi, Eun Hui Bae, Seong Kwon Ma,
The Korean journal of internal medicine, Volume 34, pp 146-155;

Treatment with paricalcitol inhibited IS-induced apoptosis by regulating MAPK, NF-κB, and Akt signaling pathway in HK-2 cells.
Ting-Bo Li, Yin-Zhuang Zhang, Wei-Qi Liu, Jie-Jie Zhang, Jun Peng, Xiu-Ju Luo,
The Korean journal of internal medicine, Volume 33, pp 313-322;

NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (NOX)-mediated oxidative stress plays a key role in promotion of oxidative injury in the cardiovascular system. The aim of this study is to evaluate the status of NOX in endothelial progenitor cells (EPCs) of hyperlipidemic patients and to assess the correlation between NOX activity and the functions EPCs. A total of 30 hyperlipidemic patients were enrolled for this study and 30 age-matched volunteers with normal level of plasma lipids served as controls. After the circulating EPCs were isolated, the EPC functions (migration, adhesion and tube formation) were evaluated and the status of NOX (expression and activity) was examined. Compared to the controls, hyperlipidemic patients showed an increase in plasma lipids and a reduction in EPC functions including the attenuated abilities in adhesion, migration and tube formation, concomitant with an increase in NOX expression (NOX2 and NOX4), NOX activity, and reactive oxygen species production. The data analysis showed negative correlations between NOX activity and EPC functions. There is a positive correlation between the NOX-mediated oxidative stress and the dysfunctions of circulating EPCs in hyperlipidemic patients, and suppression of NOX might offer a novel strategy to improve EPCs functions in hyperlipidemia.
Myeong Ho Yeon, Hee Seok Jeong, Hee Seung Lee, Jong Soon Jang, Seungho Lee, Soon Man Yoon, Hee Bok Chae, Seon Mee Park, Sei Jin Youn, , et al.
The Korean journal of internal medicine, Volume 33, pp 883-892;

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and brushing cytology are used worldwide to diagnose pancreatic and biliary malignant tumors. Liquid-based cytology (LBC) has been developed and it is currently used to overcome the limitations of conventional smears (CS). In this study, the authors aimed to compare the diagnostic value of the CellPrepPlus (CP; Biodyne) LBC method with CS in samples obtained using EUS-FNA and brushing cytology. This study prospectively enrolled 75 patients with pancreatic or biliary lesions from June 2012 to October 2013. For cytological analyses, including inadequate specimens, benign and atypical were further classified into benign, and suspicious and malignant were subcategorized as malignant. Sensitivity, specificity, accuracy, and positive predictive values (PPV) and negative predictive values (NPV) were evaluated. In the EUS-FNA based cytological analysis of pancreatic specimens, CP had a sensitivity of 60.7%; specificity, 100%; accuracy, 77.1%; PPV, 100%; and NPV, 64.5%. CS had a sensitivity of 85.7%; specificity, 100%; accuracy, 91.7%; PPV, 100%; and NPV, 83.3%. In the brushing cytology based analysis of biliary specimens, CP had sensitivity of 53.1%; specificity, 100%; accuracy, 54.5%; PPV, 100%; and NPV, 6.3%. CS had a sensitivity of 78.1%; specificity, 100%; accuracy, 78.8%; PPV, 100%; and NPV, 12.5%. Our study found that CP had a lower sensitivity because of low cellularity compared with CS. Therefore, CP (LBC) has a lower diagnostic accuracy for pancreatic EUS-FNA based and biliary brush cytology based analyses compared with CS.
, Krishna Kolappa Pillai, , Prem Kapur, Paru Kutty Pillai, Kandasamy Nagarajan
The Korean journal of internal medicine, Volume 33, pp 1203-1209;

Adverse drug reaction (ADR) is an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product. The present study was conducted in order to monitor the frequency and severity of ADR during antimicrobial therapy of septicemia.A prospective, observational, and noncomparative study was conducted over a period of 6 months on patients of septicemia admitted at a university hospital. Naranjo algorithm scale was used for causality assessment. Severity assessment was done by Hartwig severity scale.ADRs in selected hospitalized patients of septicemia was found to be in 26.5% of the study population. During the study period, 12 ADRs were confirmed occurring in 9, out of 34 admitted patients. Pediatric patients experienced maximum ADRs, 44.4%. Females experienced a significantly higher incidence of ADRs, 66.7%. According to Naranjo's probability scale, 8.3% of ADRs were found to be definite, 58.3% as probable, and 33.3% as possible. A higher proportion of these ADRs, 66.7% were preventable in nature. Severity assessment showed that more than half of ADRs were moderate. Teicoplanin was found to be the commonest antimicrobial agent associated with ADRs, followed by gemifloxacin and ofloxacin.The incidence and severity of ADRs observed in the present study was substantially high indicating the need of extra vigilant during the antimicrobial therapy of septicemia.
Baekgyu Jun, , Gab Jin Cheon, Eun Seog Kim, Eunjin Jwa, , Boo Sung Kim, Soung Won Jeong, Jae Young Jang, Sae Hwan Lee, et al.
The Korean journal of internal medicine, Volume 33, pp 1093-1102;

The aim of this study was to investigate parameters that predict radiation-induced liver disease (RILD) following stereotactic body radiotherapy (SBRT) in patients with hepatocellular carcinoma (HCC) and to identify the clinical significance of RILD.We retrospectively reviewed the medical records of 117 HCC patients who were treated by SBRT from March 2011 to February 2015. RILD was defined as elevated liver transaminases more than five times the upper normal limit or a worsening of Child-Pugh (CP) score by 2 within 3 months after SBRT. All patients were assessed at 1 month and every 3 months after SBRT.Median follow-up was 22.5 months (range, 3 to 56) after SBRT. RILD was developed in 29 of the 117 patients (24.7%). On univariate analysis, significant predictive factors of RILD were pretreatment CP score (p < 0.001) and normal liver volume (p = 0.002). Multivariate analysis showed that CP score was a significant predictor of RILD (p < 0.001). The incidence of RILD increased above a CP score of 6 remarkably. The rate of recovery from RILD decreased significantly above a CP score of 8. Survival analysis showed that CP score was an independent prognostic factor of overall survival (p = 0.001).CP score is a significant factor to predict RILD in patients with chronic liver disease. RILD can be tolerated by patients with a CP score ≤ 7. However, careful monitoring of liver function is needed for patients with a CP score 7 after SBRT.
Young-Hyo Kim, Hong-Bae Kim, Do-Hyoung Kim, Ja-Young Kim, Hyun-Young Shin
The Korean journal of internal medicine, Volume 33, pp 727-736;

Some observational epidemiologic studies have reported conflicting results on the relationship between hypnotics use and the risk of developing and/or dying from heart disease. We investigated these associations using a meta-analysis of available literatures.We searched the databases PubMed and EMBASE, along with the bibliographies of relevant articles to find additional publications in February 2016.Of 495 articles satisfying our initial criteria, two case-control studies and six cohort studies met our inclusion criteria and were included in the final analyses. Compared with never having used any kind of hypnotics, the odds ratio for overall use was 0.84 for risk of or mortality from heart disease (95% confidence interval, 0.79 to 0.89) in a random-effects meta-analysis of all eight studies. With respect to the geographical region, use of hypnotics was associated with a decreased risk or mortality of heart disease in Asia but not in Western countries. Among various types of sleep medications, zolpidem showed a decreased risk (-29%) of developing or dying from heart disease, but benzodiazepines were related with an increased risk (80%) of or mortality from heart disease.The current meta-analysis of observational epidemiological studies suggested an evidence of association between hypnotics use and a decreased risk of heart disease.
Hae Su Kim, Hee-Jin Kim, Sun-Hee Kim, Joon Young Choi, Young Hyeh Ko, Won Seog Kim, Chul Won Jung,
The Korean journal of internal medicine, Volume 32, pp 890-899;

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that typically presents in the form of skin manifestations with or without lymph node and bone marrow involvement. Given its rarity and recent recognition as a distinct pathological entity, no standard of treatment exists for this aggressive disease and its prognosis is particularly dismal.We retrospectively analyzed clinical features and treatment outcomes of patients who were diagnosed with BPDCN between 2000 and 2014.Ten patients had a median age at diagnosis of 41 years (range, 18 to 79), and seven patients were male. Sites of disease involvement were the skin (n = 7), lymph node (n = 5), bone marrow (n = 2), liver (n = 2), spleen (n = 2), and soft tissue (n = 1). Intensified chemotherapy regimens such as hyperCVAD regimen (cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine), and VPDL (vincristine, methylprednisolone, daunorubicin, L-asparaginase) were used as a first-line treatment. Although all patients treated with intensified chemotherapy showed an objective response (five patients with complete response) with median progression-free survival of 11.2 months (range 6.2 to 19.4), complete remission was not sustained for more than 2 years in any case. The response was relatively long-lived compared with previously reported CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)-like regimens, but the above regimens do not result in long-term remission.All patients treated with hyperCVAD or VPDL showed an objective response, but the duration of response was relatively short. Thus, the development of more effective induction as well as consolidation treatment strategy should be warranted to improve this rare disease entity.
So Yon Rhee, Jin Kyung Song, Suk Chul Hong, Jae Won Choi, Hee Jung Jeon, Dong Ho Shin, Eun Hee Ji, Eun-Hee Choi, Jiyeon Lee, Aram Kim, et al.
The Korean journal of internal medicine, Volume 34, pp 588-598;

As numbers of maintenance hemodialysis patients are growing, debilitating conditions of muscle wasting and atrophy are becoming some of the greatest concerns in end-stage renal disease patients. Exercise training has various potential benefits in terms of prevention of a sustained decline in functional status. This study aimed to evaluate the physical, psychological, laboratory, and dialysis-related effects of intradialytic exercise. We enrolled 22 patients from a hemodialysis center for a 6-month non-randomized prospective trial. Combination of aerobic exercise with bicycle ergometer and anaerobic exercise with elastic bands was conducted during hemodialysis. Data including physical fitness test results, dialysis-related measurements, and biochemical laboratory results were collected at baseline, 3, and 6 months. Depression and quality of life were assessed using Beck Depression Inventory and Short Form-36 health survey. After exercise completion, there were significant improvements in back muscle power, forward and backward trunk flexibility, vertical jump, elbow flexion, sit to stand test, and 6-minute walk test (p < 0.05). No significant changes were observed in dry weight, blood pressure, Kt/V, and biochemical variables, except for intradialytic hypotension (p < 0.05). For depression, Beck Depression Inventory showed statistically significant enhancement (p < 0.05). Scores of Short Form-36 health survey did not show significant increase in each domain, except for bodily pain (p < 0.05). Combined aerobic and anaerobic exercise training during dialysis was found to be effective on physical health status, intradialytic hypotension, and depression in terms of mental health. Therefore, the findings of the current study may provide an appropriate guidance for encouraging exercise by nephrologists.
Da Hea Seo, , Sujin Lee, , Seung-Il Kim, ,
The Korean journal of internal medicine, Volume 34, pp 579-587;

The aromatase inhibitors (AIs) are well known anti-hormonal therapy in endocrine-responsive breast cancer patients. It can lead to dyslipidemia and be the risk factor of cardiovascular disease due to low estrogen level. However, some recent studies comparing AIs with placebo have shown controversial results. The aim of this study was to investigate lipid profiles, measurement of carotid intima-media thickness (IMT) and the presence of plaque among endocrine-responsive breast cancer treated with AIs compared to ones that were not treated with AIs. A total of 85 postmenopausal women, who underwent breast cancer surgery during the age of 50 to 64 without history of statin use were included. There were 42 patients who were treated with AIs over 1 year (group 1) and 43 patients without AIs use (group 2). Serum total cholesterol, high density lipoprotein cholesterol, triglycerides, fasting blood glucose, carotid IMT, and presence of plaque were assessed. The baseline characteristics were similar between two groups and there was no significant difference in carotid IMT irrespective of AIs administration. However, ultrasonographic evaluation of carotid artery revealed that the presence of plaque in AI users was significantly higher than in non-AI users (66.7% vs. 41.9%, p = 0.02; odds ratio, 4.21 in adjusted model; p = 0.01). History of diabetes was also the significant risk factor for the plaque formation. There was no significant difference in lipid profile itself between two groups, but more importantly the presence of the plaque was much higher indicating possible detrimental effect of AI on cardiovascular system.
Hee-Jin Park, , Yong-Beom Park, Soo-Kon Lee,
The Korean journal of internal medicine, Volume 33, pp 1234-1240;

Red blood cell distribution width (RDW) is a value representing the heterogeneity in the size of red blood cell, and it is usually used in distinguishing types of anaemia. Recently, it was reported that it could reflect the burden of inflammation in diverse diseases and their prognosis. Hence, in this study, we investigated whether RDW may contribute to discriminating adult onset Still's disease (AOSD) from sepsis in serious febrile patients within 24 hours after hospitalization. We reviewed the medical records and enrolled 21 AOSD patients, 27 sepsis patients and 30 matched healthy controls. We collected at least two laboratory results of variables including RDW within 24 hours after hospitalization, and we calculated their mean values. Sepsis patients showed the significantly increased median white blood cell count, compared to AOSD patients (14,390.0/mm3 vs. 12,390.0/mm3 , p = 0.010). The median RDW in sepsis patients was higher than that in AOSD patients (15.0% vs. 13.3%, p = 0.001), and furthermore, the median RDW in both patient-groups was significantly higher than that in healthy controls. In contrast, the median ferritin level in sepsis patients was lower than that in AOSD patients (544.0 mg/dL vs. 3,756.6 mg/dL, p = 0.001). In multivariate analysis, RDW ≥ 14.8% (odds ratio, 17.549) and ferritin < 2,251.0 mg/dL (odds ratio, 32.414) independently suggested sepsis more than AOSD in patients initially presenting with fever requiring hospitalization. RDW might be a rapid and helpful marker for a differential diagnosis between AOSD from sepsis at an early phase.
Se Yoon Park, Jung-A Yoon,
The Korean journal of internal medicine, Volume 32, pp 805-812;

Invasive aspergillosis (IA) is one of the most common life-threatening complications in immunocompromised patients. Voriconazole is currently the drug of choice for IA treatment. However, some patients with IA suffer clinical deterioration despite voriconazole therapy. Management of voriconazole-refractory IA remains challenging; no useful recommendations have yet been made. Voriconazole-refractory IA can be further categorized as disease attributable to misdiagnosis or co-infection with another mold; inadequate blood voriconazole blood; inadequate tissue drug concentrations attributable to angioinvasion; immune reconstitution inflammatory syndrome; or infection with voriconazole-resistant Aspergillus. Hence, when encountering a case of voriconazole-refractory IA, it is necessary to schedule sequential tests to decide whether medical treatment or surgical intervention is appropriate; to adjust the voriconazole dose via drug monitoring; to seek CYP2C19 polymorphisms; to monitor serum galactomannan levels; and to examine the drug susceptibility of the causative Aspergillus species.
Sung-Han Kim, Ho-Su Lee, Hyun-Jung Lee, Sun-Mi Kim, Sung Shin, Sang-Hyoung Park, Kyung-Jo Kim, Young-Hoon Kim, Heungsup Sung, Sang-Oh Lee, et al.
The Korean journal of internal medicine, Volume 32, pp 900-909;

We evaluated the proposed clinical application of the combined interpretation of host factors and viral factors in two different cytomegalovirus (CMV) co-infection models. We prospectively enrolled all human immunodeficiency virus non-infected patients with confirmed Pneumocystitis jirovecii pneumonia (PCP) and those with suspected gastrointestinal CMV disease in a tertiary hospital. All patients underwent CMV interferon-γ releasing assay (IGRA) for CMV (T-track CMV, Lophius Biosciences). We created the 2-axis model with the CMV IGRA results as the x-axis and the results for CMV virus replication as the y-axis, and hypothesized that cases falling in the left upper quadrant (high viral load and low CMV-specific immunity) of the model would be true CMV infections. The CMV IGRA results were concealed from the attending physicians. Of 39 patients with PCP, four (10%) were classified as combined CMV pneumonia, 13 (33%) as bystander activation, and the remaining 22 (56%) as no CMV infection. The data for all four patients with PCP and CMV pneumonia fell in the left upper quadrant of the 2-axis model. Of 24 patients with suspected gastrointestinal CMV disease, 12 (50%) were classified as gastrointestinal CMV disease and the remaining 12 (50%) as bystander activation with no gastrointestinal CMV disease. The data for 11 of the 12 patients (92%) with gastrointestinal CMV disease were located in the left upper quadrant of the 2-axis model. Cases yielding low CMV IGRA results and high CMV viral replication appear to be true CMV infections. Further studies with large number of cases in different types of CMV disease should be proposed.
Yeji Han, Hye-Kyung Jung, Ji Young Chang, Chang Mo Moon, Seong-Eun Kim, Ki-Nam Shim, Sung-Ae Jung, Joo-Young Kim, Ji-Yun Bae, Sae-In Kim, et al.
The Korean journal of internal medicine, Volume 32, pp 827-835;

Duodenitis is not infrequent finding in patient undergoing endoscopy. However, hospitalized patients have a higher incidence of secondary duodenal mucosal lesions that might be related with inflammatory bowel disease (IBD), cytomegalovirus (CMV) infection, tuberculosis, immunologic disorders, or other rare infections. We aimed to identify clinicopathologic features of duodenal mucosal lesions in hospitalized patients. All hospitalized patients having duodenal mucosal lesions were identified by endoscopic registration data and pathologic data query from 2011 to 2014. The diagnostic index was designed to be sensitive; however, a detailed review of medical record and endoscopic findings was undertaken to improve specificity. Secondary duodenal lesion was defined as having specific reason to explain the duodenal lesion. Among 6,334 hospitalized patients have undergone upper endoscopy, endoscopic duodenal mucosal lesions was detected in 475 patients. Secondary duodenal lesions was 21 patients (4.4%) and the most frequent secondary cause was IBD (n = 7). The mean age of secondary group was significantly lower than that in primary group (42.3 ± 18.9 years vs. 58.5 ± 16.8 years, p = 0.00), and nonsteroidal anti-inflammatory drugs were less frequently used in secondary group, but there was no differences of gender or presence of Helicobacter pylori. The involvement of distal part of duodenum including postbulbitis or panduodenitis was more frequently detected in secondary group than in primary group. By multivariate regression analysis, younger age of 29 years and the disease extent were significant predictors for the secondary mucosal lesions. Secondary duodenal mucosal lesions with different pathophysiology, such as IBD or CMV infection, are rare. Disease extent and age seems the most distinctive feature of secondary duodenal mucosal lesions.
Chung Hee Baek, Hyosang Kim, Seung Don Baek, Mun Jang, Wonhak Kim, Won Seok Yang, Duck Jong Han,
The Korean journal of internal medicine, Volume 33, pp 356-366;

Kidney transplantation (KT) reportedly provides a significant survival advantage over dialysis in diabetic patients. However, KT outcome in diabetic patients compared with that in non-diabetic patients remains controversial. In addition, owing to recent improvements in the outcomes of KT and management of cardiovascular diseases, it is necessary to analyze outcomes of recently performed KT in diabetic patients. We reviewed all diabetic patients who received living donor KT between January 2008 and December 2011. Each patient was age- and sex-matched with two non-diabetic patients who received living donor KT during the same period. The outcomes of living donor KT were compared between diabetic and non-diabetic patients. Among 887 patients, 89 diabetic patients were compared with 178 non-diabetic patients. The incidence of acute rejection was not different between the diabetic and non-diabetic patients. Urinary tract infection and other infections as well as cardiovascular events occurred more frequently in diabetic patients. However, diabetes, cardiovascular disease, and infection were not significant risk factors of graft failure. Late rejection (acute rejection after 1 year of transplantation) was the most important risk factor for graft failure after adjusting for diabetes mellitus (DM), human leukocyte antigen mismatch, rejection and infection (hazard ratio, 56.082; 95% confidence interval, 7.169 to 438.702; p < 0.001). Mortality was not significantly different between diabetic and non-diabetic patients (0 vs. 2, p = 0.344 by log-rank test). End-stage renal disease patients with DM had favorable outcomes with living donor kidney transplantation.
Eun Chung, Kihoon Park, Jo Heon Kim, Nam Ik Han, Young Sok Lee, Si Hyun Bae, Chung-Hwa Park
The Korean journal of internal medicine, Volume 32, pp 1098-1100;

Ja Young Lee,
The Korean journal of internal medicine, Volume 32, pp 790-797;

The radiocephalic arteriovenous fistula (AVF) provides optimal vascular access for hemodialysis; it has a higher long-term patency rate and fewer complications than other vascular access methods. However, the AVF has a high primary failure rate. The presence of small-diameter vessels at anastomosis sites is an important risk factor for AVF failure. However, in a recent study, despite selecting an adequate artery and vein for creating an AVF by routine preoperative vascular mapping, AVF maturation and primary failure occurred. Thus, pre-existing arteriosclerosis at AVF anastomosis sites likely contributes to AVF failure. In this review, we discuss the relationship between pathologic changes and AVF patency in hemodialysis patients. Because arteriosclerosis of the major arteries such as the coronary and carotid arteries is associated with cardiovascular mortality, we also review the impact of arteriosclerosis of upper arm arteries at AVF anastomosis sites on cardiovascular mortality in hemodialysis patients.
Jin Young Kim, Chi Heum Cho,
The Korean journal of internal medicine, Volume 32, pp 798-804;

Epithelial ovarian cancer is the eighth most common cause of cancer-related deaths in women because most patients present with advanced stage disease at the time of diagnosis. Although cytoreductive surgery and platinum-based chemotherapy remain the gold standards of treatment, the recurrence rate of ovarian cancer remains high. Attempts to improve this standard two-drug chemotherapy by adding a third cytotoxic drug have failed to affect either progression-free survival or overall survival and have resulted in an increase in toxic side effects. Some anti-angiogenic agents, poly(ADP-ribose) polymerase, and immune checkpoint inhibitors have shown efficacy in early stages of development for the treatment of epithelial ovarian cancer. As demonstrated in recent clinical trials, the use of bevacizumab, cediranib, pazopanib, olaparib, and rucaparib, either alone or in combination with conventional cytotoxic agents, improves progression-free survival. Trials on immune checkpoint inhibitors such as nivolumab have revealed prolonged responses in a small set of ovarian cancer cases but require further exploration. In this review, we discuss the role of targeted therapies against ovarian cancer, including the use of immune checkpoint inhibitors.
, Joon Young Chang, Koon Soon Kim,
The Korean journal of internal medicine, Volume 32, pp 780-789;

Thyroid cancer is one of the most common malignancies of endocrine organs, and its incidence rate has increased steadily over the past several decades. Most differentiated thyroid tumors derived from thyroid epithelial cells exhibit slow-growing cancers, and patients with these tumors can achieve a good prognosis with surgical removal and radioiodine treatment. However, a small proportion of patients present with advanced thyroid cancer and are unusually resistant to current drug treatment modalities. Thyroid tumorigenesis is a complex process that is regulated by the activation of oncogenes, inactivation of tumor suppressors, and alterations in programmed cell death. Mitochondria play an essential role during tumor formation, progression, and metastasis of thyroid cancer. Recent studies have successfully observed the mitochondrial etiology of thyroid carcinogenesis. This review focuses on the recent progress in understanding the molecular mechanisms of thyroid cancer relating to altered mitochondrial metabolism.
Min Soo Cho,
The Korean journal of internal medicine, Volume 32, pp 769-779;

The introduction of drug-eluting stents (DES) in the practice of percutaneous coronary intervention (PCI) has substantially reduced angiographic and clinical restenosis but is associated with an increasing propensity for very late stent thrombosis (ST). Among several clinical, lesion, or procedure-related predictors of ST, early discontinuation of dual antiplatelet therapy (DAPT) is the most important factor for DES-associated late thrombosis; therefore, the optimal duration of DAPT is a major issue to be critically considered in the current DES era. Given that the benefit and risk of longer duration DAPT should be simultaneously considered, the optimal DAPT period following DES implantation has been controversial. Several small-to-medium sized randomized clinical trials and observational registries have indicated that short-term DAPT (< 6 months) is not inferior to 12-month DAPT with fewer bleeding events, whereas prolonged duration of DAPT (> 12 months) failed to prove its superiority. However, compelling evidence from a landmark DAPT trial has clearly demonstrated the efficacy of prolonged DAPT up to 30 months in terms of preventing ST and major cardiovascular adverse events at the expense of major bleeding. In addition, coupled with various risk algorithms, a more individualized approach to balance the efficacy and safety of optimal DAPT duration has been emphasized. In this review article, we systematically summarize the cumulative evidence from key clinical studies and try to help the physician make decisions on the optimal duration of DAPT in contemporary PCI practice.
, , Jeong Hwan Kim, , Hyung Seok Park, Chan Sup Shim
The Korean journal of internal medicine, Volume 32, pp 819-826;

Some people have difficulty tolerating upper endoscopy. The cause of and risk factors for this are not well known. The aim of this study was to investigate the factors involved in poor cooperation during screening upper endoscopy. A total of 4,422 subjects who underwent a health inspection with upper endoscopy carried out by a single experienced endoscopist were included. We retrospectively investigated subjects' self-reporting questionnaires and medical records, including endoscopic and histologic findings. The examinees' cooperation and the completeness of endoscopic examination were evaluated based on the operator's subjective judgment. Examinee cooperation during the endoscopic procedure was poor in 358 out of 4,422 subjects (8.1%). Of the subjects with poor cooperation, the endoscopic examination was incomplete in 36 subjects (10.1%). Multivariate analysis revealed that young age (< 40 years), female sex, high body mass index (≥ 25), hiatal hernia, and procedural sedation using midazolam were independent risk factors for poor cooperation. Cooperation during screening upper endoscopy was poor in a considerable number of examinees. Endoscopists must keep in mind that examinee cooperation is more likely to be poor in the young, obese people, women, patients with hiatal hernias, and those who receive procedural sedation.
Soo-Taek Uh, So My Koo, Yangki Kim, Kiup Kim, Sungwoo Park, An Soo Jang, Dojin Kim, Yong Hoon Kim,
The Korean journal of internal medicine, Volume 32, pp 865-874;

Diesel exhaust particles (DEPs) lead to elevation of reactive oxygen species, which can activate the nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain 3 (NLRP3)-inf lammasome. In this study, we elucidated whether NLRP3 -inf lammasome is activated by DEPs and whether antioxidants (N-acetylcysteine [NAC]) could inhibit such activation. RAW 264.7 cells and ex vivo lung tissues explants obtained from elastase-induced emphysema animal models were stimulated with cigarette smoking extract (CSE), DEPs, and lipopolysaccharide, and levels of interleukin-1β (IL-1β), caspase-1 and nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain (NLRP3)-inflammasome were assessed by Western blotting and immunohistochemistry. NAC and caspase-1 inhibitor suppressed CSE- and DEP-induced secretion of IL-1β in RAW 264.7 cells. The expression levels of the NLRP3-inflammasome and caspase-1 were upregulated in RAW 264.7 cells by stimulation with CSE and DEPs and were inhibited by NAC. CSE and DEPs increased the secretion of IL-1β in lung tissues from both the normal and elastase-induced emphysema groups. The secretion of IL-1β by CSE and DEPs was increased in the elastin-induced emphysema group more than that in the normal group (CSE: 309 ± 19 pg/mL vs. 151 ± 13 pg/mL, respectively, p < 0.05; DEP: 350 ± 24 pg/mL vs. 281 ± 15 pg/mL, respectively, p < 0.05). NAC inhibited CSE- and DEP-induced IL-1β secretion in both the normal and elastase-induced emphysema groups. NLRP3-inflammasome expression as determined by immunohistochemistry was increased by CSE and DEPs in both the normal and elastin-induced emphysema groups, and was suppressed by NAC. The NLRP3-inf lammasome is activated by DEPs in ex vivo tissue explants from elastase-induced emphysema animal model, and this activation is inhibited by NAC.
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