Two-Year Changes in Diabetic Kidney Disease Phenotype and the Risk of Heart Failure: A Nationwide Population-Based Study in Korea

Background@#Diabetic kidney disease (DKD) is a risk factor for hospitalization for heart failure (HHF). DKD could be classified into four phenotypes by estimated glomerular filtration rate (eGFR, normal vs. low) and proteinuria (PU, negative vs. positive). Also, the phenotype often changes dynamically. This study examined HHF risk according to the DKD phenotype changes across 2-year assessments. @*Methods@#The study included 1,343,116 patients with type 2 diabetes mellitus (T2DM) from the Korean National Health Insurance Service database after excluding a very high-risk phenotype (eGFR <30 mL/min/1.73 m2) at baseline, who underwent two cycles of medical checkups between 2009 and 2014. From the baseline and 2-year eGFR and PU results, participants were divided into 10 DKD phenotypic change categories. @*Results@#During an average of 6.5 years of follow-up, 7,874 subjects developed HHF. The cumulative incidence of HHF from index date was highest in the eGFRlowPU– phenotype, followed by eGFRnorPU+ and eGFRnorPU–. Changes in DKD phenotype differently affect HHF risk. When the persistent eGFRnorPU– category was the reference, hazard ratios for HHF were 3.10 (95% confidence interval [CI], 2.73 to 3.52) in persistent eGFRnorPU+ and 1.86 (95% CI, 1.73 to 1.99) in persistent eGFRlowPU–. Among altered phenotypes, the category converted to eGFRlowPU+ showed the highest risk. In the normal eGFR category at the second examination, those who converted from PU– to PU+ showed a higher risk of HHF than those who converted from PU+ to PU–. @*Conclusion@#Changes in DKD phenotype, particularly with the presence of PU, are more likely to reflect the risk of HHF, compared with DKD phenotype based on a single time point in patients with T2DM.

Hip Fracture Risk According to Diabetic Kidney Disease Phenotype in a Korean Population

Background@#Diabetic kidney disease (DKD) is associated with an elevated risk of fractures. However, little is known about the association between proteinuric or non-proteinuric DKD and the risk of hip fracture. Thus, we investigated the incidence of hip fractures among Korean adults with type 2 diabetes mellitus (T2DM) stratified by DKD phenotype. @*Methods@#In this retrospective cohort study using the Korean National Health Insurance Service database, patients with T2DM who received at least one general health checkup between 2009 and 2012 were followed until the date of hip fracture, death, or December 31, 2018. We classified the DKD phenotype by proteinuria and estimated glomerular filtration rate (eGFR), as follows: no DKD (PU−GFR−), proteinuric DKD with normal eGFR (PU+GFR−), non-proteinuric DKD with reduced eGFR (PU−GFR+), and proteinuric DKD with reduced eGFR (PU+GFR+) @*Results@#The cumulative incidence of hip fractures was highest in the PU+GFR+ group, followed by the PU−GFR+ group and the PU+GFR− group. After adjustment for confounding factors, the hazard ratio (HR) for hip fracture was still highest in the PU+GFR+ group. However, the PU+GFR− group had a higher HR for hip fracture than the PU−GFR+ group (PU+GFR+ : HR, 1.69; 95% confidence interval [CI], 1.57 to 1.81; PU+GFR− : HR, 1.37; 95% CI, 1.30 to 1.46; PU−GFR+ : HR, 1.20; 95% CI, 1.16 to 1.24 using the PU−GFR− group as the reference category). @*Conclusion@#The present study demonstrated that DKD was significantly associated with a higher risk of hip fracture, with proteinuria as a major determinant.

Comparative Effects of Sodium-Glucose Cotransporter 2 Inhibitor and Thiazolidinedione Treatment on Risk of Stroke among Patients with Type 2 Diabetes Mellitus

Background@#Although cardiovascular outcome trials using sodium-glucose cotransporter-2 inhibitors (SGLT-2i) showed a reduction in risk of 3-point major adverse cardiovascular events (MACE), they did not demonstrate beneficial effects on stroke risk. Additionally, meta-analysis showed SGLT-2i potentially had an adverse effect on stroke risk. Contrarily, pioglitazone, a type of thiazolidinedione (TZD), has been shown to reduce recurrent stroke risk. Thus, we aimed to compare the effect of SGLT-2i and TZD on the risk of stroke in type 2 diabetes mellitus (T2DM) patients. @*Methods@#Using the Korean National Health Insurance Service data, we compared a 1:1 propensity score-matched cohort of patients who used SGLT-2i or TZD from January 2014 to December 2018. The primary outcome was stroke. The secondary outcomes were myocardial infarction (MI), cardiovascular death, 3-point MACE, and heart failure (HF). @*Results@#After propensity-matching, each group included 56,794 patients. Baseline characteristics were well balanced. During the follow-up, 862 patients were newly hospitalized for stroke. The incidence rate of stroke was 4.11 and 4.22 per 1,000 person-years for the TZD and SGLT-2i groups respectively. The hazard ratio (HR) of stroke was 1.054 (95% confidence interval [CI], 0.904 to 1.229) in the SGLT-2i group compared to the TZD group. There was no difference in the risk of MI, cardiovascular death, 3-point MACE between groups. Hospitalization for HF was significantly decreased in SGLT-2i-treated patients (HR, 0.645; 95% CI, 0.466 to 0.893). Results were consistent regardless of prior cardiovascular disease. @*Conclusion@#In this real-world data, the risk of stroke was comparable in T2DM patients treated with SGLT-2i or TZD.

Discordance in Bone Mineral Density between the Lumbar Spine and Femoral Neck Is Associated with Renal Dysfunction

Purpose@#Bone mineral density (BMD) determined by dual-energy X-ray absorptiometry is considered a gold standard for diagnosing osteoporosis. Some people show discordance in BMD values measured at the femur and that at the lumbar spine (LS). The aim of the present study was to investigate whether differences in BMD T-scores between the LS and femur neck (FN) are associated with renal dysfunction in the general population of Korea. @*Materials and Methods@#We analyzed national data for 17306 adults from the Korean National Health and Nutrition Examination Survey conducted between 2008 and 2011. BMD T-score differences between LS and FN (termed BMD offset) were calculated by subtracting FN T-scores from LS T-scores. Diminished renal function was defined as estimated glomerular filtration rates (eGFR) less than 60 mL/min/1.73 m2 . @*Results@#Among those aged ≥50 years, BMD offset was negatively associated with eGFR levels. Additionally, eGFR levels decreased linearly across increasing BMD offset quartiles. Men and women with an offset of >1.5 showed a 4.79-times and 2.51-times higher risk of renal dysfunction, respectively, compared to individuals with an offset of ≤0, after adjusting for age, body mass index, educational level, current smoking, and physical activity. In contrast, there was little evidence of an association between renal dysfunction and BMD offset in subjects aged <50 years. @*Conclusion@#Discordance between LS and FN BMDs was significantly associated with renal dysfunction in subjects aged ≥50 years. When assessing bone health in older chronic kidney disease patients, physicians should consider the possibility of BMD discordance between LS and FN.

Metabolic Subtyping of Adrenal Tumors: Prospective Multi-Center Cohort Study in Korea

Background@#Conventional diagnostic approaches for adrenal tumors require multi-step processes, including imaging studies and dynamic hormone tests. Therefore, this study aimed to discriminate adrenal tumors from a single blood sample based on the combination of liquid chromatography-mass spectrometry (LC-MS) and machine learning algorithms in serum profiling of adrenal steroids. @*Methods@#The LC-MS-based steroid profiling was applied to serum samples obtained from patients with nonfunctioning adenoma (NFA, n=73), Cushing’s syndrome (CS, n=30), and primary aldosteronism (PA, n=40) in a prospective multicenter study of adrenal disease. The decision tree (DT), random forest (RF), and extreme gradient boost (XGBoost) were performed to categorize the subtypes of adrenal tumors. @*Results@#The CS group showed higher serum levels of 11-deoxycortisol than the NFA group, and increased levels of tetrahydrocortisone (THE), 20α-dihydrocortisol, and 6β-hydroxycortisol were found in the PA group. However, the CS group showed lower levels of dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) than both the NFA and PA groups. Patients with PA expressed higher serum 18-hydroxycortisol and DHEA but lower THE than NFA patients. The balanced accuracies of DT, RF, and XGBoost for classifying each type were 78%, 96%, and 97%, respectively. In receiver operating characteristics (ROC) analysis for CS, XGBoost, and RF showed a significantly greater diagnostic power than the DT. However, in ROC analysis for PA, only RF exhibited better diagnostic performance than DT. @*Conclusion@#The combination of LC-MS-based steroid profiling with machine learning algorithms could be a promising one-step diagnostic approach for the classification of adrenal tumor subtypes.

Real-World Experience with Pembrolizumab Treatment in Patients with Heavily Treated Recurrent Gynecologic Malignancies

Purpose@#We evaluated the efficacy and safety of pembrolizumab in patients with recurrent gynecologic cancers in real-world practice. @*Materials and Methods@#We conducted a retrospective, single-institution study of patients with recurrent gynecologic malignancies treated with pembrolizumab. The primary endpoints were the objective response rate (ORR) and safety. @*Results@#Thirty-one patients treated with pembrolizumab were included. The primary disease sites were the uterine cervix (n=18), ovaries (n=8), and uterine corpus (n=5). Fifteen of the 31 patients (48%) had an Eastern Cooperative Oncology Group performance status of ≥2. The median number of prior chemotherapy lines was 2 (range, 1–6), and 14 of 31 patients (45%) had received ≥ 3 prior lines of chemotherapy. The overall ORR was 22.6%: specifically, 22.3% (4 of 18 patients), 12.5% (1 of 8 patients), and 40% (2 of 5 patients) for cervical, ovarian, and endometrial cancers, respectively. During a median follow-up of 4.7 months (range, 0.2–35.3), the median time to response was 1.9 months (range, 1.4–5.7). The median duration of response was not reached (range, 8.8-not reached).The median progression-free survival was 2.5 months (95% confidence interval, 1.7-not reached). Adverse events occurred in 20 patients (64.5%), and only 3 (9.7%) were grade ≥3. There was one case of suspicious treatment-related mortality, apart from which most adverse events were manageable. @*Conclusion@#In real-world practice, pembrolizumab was feasible and effective in heavily treated recurrent gynecologic cancer patients with poor performance status who may not be eligible for enrollment in clinical trials.

Anti-platelet effects of epigallocatechin-3-gallate in addition to the concomitant aspirin, clopidogrel or ticagrelor treatment

BACKGROUND/AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Guide-Wire Assisted Endobiliary Forceps Biopsy Sampling

No abstract available.

Post-Traumatic Cognition Mediates the Relationship between a History of Sexual Abuse and the Post-Traumatic Stress Symptoms in Sexual Assault Victims

More than half of all sexual assault victims report experiencing sexual victimization more than once. The aim of this paper was to determine the role post-traumatic cognition plays in the relationship between a history of sexual abuse and post-traumatic stress symptoms in sexual assault victims. The relationship between a history of sexual assault and the severity of post-traumatic stress symptoms was investigated retrospectively using data from a sexual assault crisis center in Korea. Data on psychological symptoms were collected in person at the initial assessment and by telephone 1 month later using the Post-traumatic Cognitions Inventory and the Post-traumatic Stress Disorder Symptoms Scale: Self-report Version. Of 105 women included in the analysis, 10 (9.5%) reported prior sexual abuse and were classified as sexually revictimized. Revictimized women had more post-traumatic negative cognition at initial assessment (t = −2.98; P = 0.004) and more post-traumatic symptoms at 1 month follow-up (t = −2.39; P = 0.019) than singly victimized women. At 1 month follow-up, the severity of post-traumatic stress symptoms had increased in revictimized women but had decreased slightly in singly victimized women. Negative post-traumatic cognition fully mediated the association between a history of sexual abuse and the severity of post-traumatic stress symptoms. Early detection of sexually revictimized women and tailored service and treatment intervention is needed to better serve this group of victims. Interventions targeted at preventing revictimization or post crime victimization may also help victims recover from the trauma and prevent future abuse.

Spontaneous Perforation of Common Bile Duct: Abscess Formation Presenting as a Choledochal Cyst

Spontaneous perforation of the bile duct without any traumatic or iatrogenic injury is extremely rare. We report a case of abscess formation related to spontaneous perforation of the common bile duct by a gallstone, mimicked a cholecochal cyst.

HPV Knowledge, HPV Vaccination Intention, and Barriers on HPV Vaccination in Male Undergraduate Students of Health Department and Non-health Department

PURPOSE: The aim of this study was to identify the level of Human papillomavirus (HPV) knowledge, intention of HPV vaccination, and barriers on HPV vaccination among male undergraduate students of Health department and Non-health department. METHODS: A total of 149 male undergraduate students responded to self-administered questionnaires about their HPV knowledge, HPV vaccination intention, and their barriers on HPV vaccination. ANOVA, t-test and χ2 test (Fisher's exact test) were used for data analysis. RESULTS: Mean score of HPV knowledge was 3.39±3.05, and there was significant difference between Health department (4.15±3.08) and Non-health department (2.58±2.82) in HPV knowledge (t=3.241, p=.001). There was no significant difference in HPV vaccination acceptance between the two groups. The barriers on HPV vaccination were 'lack of information about HPV vaccine efficacy' and 'lack of information about HPV vaccination time and strategy', and there were significant differences in barriers on HPV vaccination between the two groups. CONCLUSION: The knowledge on HPV was low, and HPV vaccination was hindered due to lack of information about HPV vaccine despite their intention to obtain HPV vaccine. HPV education to promote HPV vaccination should be targeted among male students.

Genetic Variations of Drug Transporters Can Influence on Drug Response in Patients Treated with Docetaxel Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Dose-limiting toxicities of docetaxel are widely considered to be neutropenia, anemia, skin toxicity, and nausea. One of the factors that limit the use of docetaxel is its unpredictability of inter-individual variation in toxicity. MATERIALS AND METHODS: In order to identify the genetic factors that affect the risk of docetaxel-induced toxicities, we recruited patients who received docetaxel chemotherapy. We genotyped 92 patients with single-nucleotide polymorphisms (SNPs) in 5 genes: CYP3A4 (CYP3A4*1B, CYP3A4*18, and CYP3A4*3), CYP3A5 (CYP3A5*2 and CYP3A5*3), ABCB1 (C1236T, G2677G/T, and C3435T), SLCO1B3 (rs11045585), and ABCC2 (rs12762549). RESULTS: Out of 92 patients, 70 had grade 3 or 4 neutropenia; 4 had grade 1 or 2; and 18 had no toxicity (76.1%, 4.3%, and 19.6%, respectively). The findings of the SNP analysis showed that patients with TT genotype of ABCB1 3435C>T polymorphism showed significantly higher risk of neutropenia and anemia (p=0.029 and p=0.044, respectively). There were significant associations between docetaxel-induced leucopenia and 2677G/T of ABCB1 and rs12762549 of ABCC2 (p=0.025 and p=0.028, respectively). In a multivariate analysis, we observed that patients carrying 2677G>T in ABCB1might be associated with higher risk of chemo-resistance when treated with docetaxel (odds ratio [OR], 6.48; confidence interval, 1.92 to 21.94; p=0.003). In a subgroup analysis of non-small cell lung cancer patients, a significant association of tumor response with G2677T/A (OR, 4.54) in ABCB1 and SLCO1B3 (OR, 9.44) was observed. CONCLUSION: Our data suggest that ABCB1 (2677G/T) and SLCO1B3 (rs11055585) might be major genetic predictors of docetaxel-related toxicities in patients receiving docetaxel chemotherapy.

Influencing Factors on Presenteeism of Clinical Nurses / 한국직업건강간호학회지

PURPOSE: This study was conducted to identify the influencing factors of job stress, self-efficacy, and organizational culture to presenteeism in clinical nurses. METHODS: A descriptive correlation research design was used for the this study. The subjects were 245 nurses working at the hospital in S, A and C City, from August 1st to October 30th 2014. Data were analyzed using t-test, ANOVA, Scheffe's test, stepwise multiple regression by SPSS 21.0 program. RESULTS: Job impairment indicated a significant positive relationship to job stress (p=.009), health problem (p<.001), and indicated significant negative relationship to self-efficacy (p<.001), innovative-oriented (p<.001), affiliative-oriented (p=.002), task-oriented (p=.026) in organizational culture. Significant factors of influencing to presenteeism were self-efficacy (p<.001, beta=-.363), culture of task-oriented (p<.001, beta=-.248) in organizational culture, and health problem (p=.002, beta=.187). CONCLUSION: Self-efficacy was defined as a variable to influence on presenteeism, and developing of strategies and program to strengthen self-efficacy and task-oriented of organizational culture in nursing is helpful to reduce the presenteeism of clinical nurses.

CYP3A5*3 Polymorphism and Its Clinical Implications and Pharmacokinetic Role

The cytochrome P450 (CYP) 3A subfamily is estimated to participate in the biotransformation of 50% of the currently prescribed drugs. Four members of the CYP3A subfamily have been identified in humans: CYP3A4, CYP3A5, CYP3A7, and CYP3A43. Initial data suggested that CYP3A5 accounts for only a small proportion of the total hepatic CYP3A in about 20% of samples, but it was later revealed that CYP3A5 represents more than 50% of the total CYP3A amount in some individuals. Several genetic variants have been described for the CYP3A5 gene, of which the CYP3A5*3 allele (gA6986G), the most common form and leading to the loss of CYP3A5 activity, has been extensively investigated in the aspect of pharmacokinetics and disease risk. This review summarized the molecular characteristics of the CYP3A5 gene, and discusses the association of the CYP3A5*3 polymorphism with disease risks such as cancer and hypertension, along with its role in the pharmacokinetics of CYP3A substrates.

Hemodynamics on Three-Phase Dynamic CT and Ultrasonographic Echogenicity of Small Hepatic Cavernous Hemangioma

PURPOSE: The purpose of this study is to investigate the correlation between hemodynamics on three-phase CT and ultrasonography echogenecity of small hepatic cavernous hemangiomas (0.5 - 3 cm). MATERIALS AND METHODS: A total of 158 hepatic cavernous hemangiomas in 139 patients with normal liver parenchyma, who underwent ultrasonography and dynamic CT, were analyzed retrospectively over a six-year period. Two radiologists performed independent analysis of the echogenecity (hyperechoic to hypoechoic) on ultrasonography and hemodynamics (slow to rapid) on CT images using five-grade scales. Correlation between ultrasonography echogenecity scores and CT hemodynamics scores was examined using Spearman's correlation analysis. CT hemodynamics scores were also evaluated with respect to the size of the hepatic cavernous hemangiomas using Spearman's correlation analysis. RESULTS: The ultrasonography echogenecity scores showed significant correlation with the CT hemodynamics scores (r=0.364, p0.05). CONCLUSIONS: More rapid filling of contrast materials in small hepatic cavernous hemangiomas on dynamic CT suggests a greater decrease in echogenecity on ultrasonography and the echogenicity of small hepatic cavernous hemangiomas on ultrasonography can be predicted based on their hemodynamics on dynamic CT.

Apoptosis of Human Islet Cells by Cytokines

FasL, perforin, TNFalpha, IL-1 and NO have been considered as effector molecule(s) leading to beta-cell death in autoimmune diabetes. However, the real culprit(s) of beta-cell destruction have long been elusive despite intense investigation. Previously we have suggested IFNgamma/TNFalpha synergism as the final effector molecules in autoimmune diabetes of NOD mice. A combination of IFNgamma and TNFalpha but neither cytokine alone, induced classical caspase-dependent apoptosis in murine insulinoma and pancreatic islet cells. IFNgamma treatment conferred susceptibility to TNFalpha-induced apoptosis on otherwise resistant murine insulinoma cells by STAT1 activation followed by IRF-1 induction. Here we report that IFNgamma/TNFalpha synergism induces apoptosis of human pancreatic islet cells. We also observed STAT1 activation followed by IRF-1 induction by IFNgamma treatment in human islet cells. Taken together, we suggest that IFNgamma/TNFalpha synergism could be involved in human islet cell death in type 1 diabetes, similar to murine type 1 diabetes.

Diabetes Education Recognition Program / 임상당뇨병

The Committee of Education of the Korean Diabetes Association discussed the need to develop the Diabetes Education Recognition Program. In 2011, the current certification program was reviewed and a survey was conducted to improve the Diabetes Education Recognition Program. This improved program will be a standard for qualified diabetes education for diabetes educators and institutes, and will ultimately become a national standard for diabetes education.

Eosinophilic Infiltration in the Liver: Unusual Manifestation of Hepatic Segmental Involvement

Eosinophilic infiltration in the liver is not a rare disease and it is usually presented as multiple, small, ill defined, oval or round, low attenuated lesions on portal phase of computed tomography. We reported case of hepatic eosinophilic infiltration in the liver, as an unusual manifestation of segmental involvement.

Preoperative Assessment of Cardiac Risk in the Patient with Diabetes / 임상당뇨병

Approximately 50% of people with diabetes will at some point undergo surgery related to their disease. Since patients with diabetes mellitus are four times more likely to have silent ischemia and coronary artery disease compared to the risk of non-diabetic patients, they are at a higher risk for perioperative complications. Preoperative evaluation can identify many patients at increased risk of an adverse cardiac event, and appropriate perioperative management can reduce that risk. Although there is great potential to reduce perioperative cardiovascular risk, it is also impractical to perform cardiovascular testing prior to non-cardiac surgery in all patients. Therefore, it is important to determine perioperative risk and the appropriateness of cardiac testing and to provide prophylactic treatment to reduce risk. Perioperative cardiac risk stratification is determined by comorbidity, other cardiovascular risk factors, functional status, and type of surgery. By categorizing the cardiac risk, physicians can perform surgery in low risk patients without the need for cardiac testing. When preoperative risk assessment identifies intermediate- and high-risk patients, further cardiac testing might be warranted. This article reviews the perioperative evaluation of patients with diabetes with a clinical focus on cardiovascular risk.

Severe Hypertriglyceridemia in Diabetic Ketoacidosis Accompanied by Acute Pancreatitis: Case Report

We report a case of diabetic ketoacidosis (DKA) and hypertriglyceridemia (severely elevated to 15,240 mg/dL) complicated by acute pancreatitis, which was treated successfully with insulin therapy and conservative management. A 20-yr-old woman with a history of type 1 diabetes came to the emergency department 7 months after discontinuing insulin therapy. DKA, severe hypertriglyceridemia and acute pancreatitis were diagnosed, with DKA suspected of contributing to the development of the other conditions. In Korea, two cases of DKA-induced hypertriglyceridemia and 13 cases of hypertriglyceridemia-induced acute pancreatitis have been previously reported separately.