Background: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. Methods: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). Results: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). Conclusion There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications.

Background: Diabetes mellitus (DM) is one of the most common endocrine diseases, and the relationship between diabetes and skin diseases is well-known and its mechanisms have been studied. Objective: This study aimed to examine the association between DM and skin diseases. Methods: We used the medical record database provided by the National Health Insurance Service. We constructed a cohort with 1,197,225 patients diagnosed with type 2 DM from 2011 to 2015. We analyzed 3,992,368 medical records of patients with DM who visited the hospital from January 1, 2009 to December 13, 2018 with skin and subcutaneous tissue diseases (ICD-10 code, L00-L99). After that, we compared the changes in skin and subcutaneous tissue diseases before and after the diagnosis of type 2 DM. Results: The number of patients with skin diseases, after the diagnosis of type 2 DM was 1,629,756 (50.6%). The frequency of skin diseases increased after the diagnosis of type 2 DM compared to that before the diagnosis. Particularly, infectious diseases (＋29.03%,p＜0.001), vesiculobullous diseases (＋33.13%, p＜0.001) and ulcerrelated diseases (pressure sores [＋530.18%], and lower extremity ulcers [＋321.56%], p＜0.001) increased sharply whereas dermatitis and eczematous diseases (−9.96%, p＜0.001) and urticaria (−12.99%, p＜0.001) decreased. Conclusion Skin diseases increased following the diagnosis of diabetes, and there were changes in the pattern of skin diseases before and after the diagnosis of diabetes.

The increased expression of receptors for advanced glycation endproduct (RAGE) is known as a key player in the progression of vascular remodeling.However, the precise signal pathways regulating RAGE expression in vascular smooth muscle cells (VSMCs) in the injured vasculatures are unclear. Given the importance of mitogen-activated protein kinase (MAPK) signaling in cell proliferation, we investigated the importance of MAPK signaling in high-mobility group box 1 (HMGB1)-induced RAGE expression in VSMCs. In HMGB1 (100 ng/ml)-stimulated human VSMCs, the expression of RAGE mRNA and protein was increased in association with an increase in AGE-induced VSMC proliferation. The HMGB1-induced RAGE expression was attenuated in cells pretreated with inhibitors for ERK (PD98059, 10 μM) and p38 MAPK (SB203580, 10 μM) as well as in cells deficient in ERK and p38 MAPK using siRNAs, but not in cells deficient of JNK signaling. In cells stimulated with HMGB1, the phosphorylation of ERK, JNK, and p38 MAPK was increased. This increase in ERK and p38 MAPK phosphorylation was inhibited by p38 MAPK and ERK inhibitors, respectively, but not by JNK inhibitor. Moreover, AGE-induced VSMC proliferation in HMGB1-stimulated cells was attenuated in cells treated with ERK and p38 MAPK inhibitors. Taken together, our results indicate that ERK and p38 MAPK signaling are involved in RAGE expression in HMGB1-stimulated VSMCs. Thus, the ERK/p38 MAPKRAGE signaling axis in VSMCs was suggested as a potential therapeutic target for vascular remodeling in the injured vasculatures.

BACKGROUND/OBJECTIVES: Premenstrual syndrome (PMS) is a disorder characterized by repeated emotional, behavioral, and physical symptoms before menstruation, and the exact cause and mechanism are uncertain. Hyperprolactinemia interferes with the normal production of estrogen and progesterone, leading to PMS symptoms. Thus, we judged that the inhibition of prolactin hypersecretion could mitigate PMS symptoms.MATERIALS/METHODS: Hordeum vulgare L. extract (HVE), Chrysanthemum zawadskii var. latilobum extract (CZE), and Lomens-P0 the mixture of these extracts were tested in subsequent experiments. The effect of extracts on prolactin secretion at the in vitro level was measured in GH3 cells. Nitric oxide and pro-inflammatory mediator expression were measured in RAW 264.7 cells to confirm the anti-inflammatory effect. Also, the hyperprolactinemic Institute for Cancer Research (ICR) mice model was used to measure extract effects on prolactin and hormone secretion and uterine inflammation. RESULTS: Anti-inflammatory effects of and prolactin secretion suppress by HVE and CZE were confirmed through in vitro experiments (P < 0.05). Treatment with Lomens-P0 inhibited prolactin secretion (P < 0.05) and restored normal sex hormone secretion in the hyperprolactinemia mice model. In addition, extracts significantly inhibited the expression of pro-inflammatory biomarkers, including interleukin-1β, and -6, tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2 (P < 0.01). We used high-performance liquid chromatography analyses to identify tricin and chlorogenic acid as the respective components of HVE and CZE that inhibit prolactin secretion. The Lomens-P0, which includes tricin and chlorogenic acid, is expected to be effective in improving PMS symptoms in the human body. CONCLUSIONS The Lomens-P0 suppressed the prolactin secretion in hyperprolactinemia mice, normalized the sex hormone imbalance, and significantly suppressed the expression of inflammatory markers in uterine tissue. This study suggests that Lomens-P0 may have the potential to prevent or remedy materials to PMS symptoms.

Ticks can transmit pathogenic bacteria, protozoa, and viruses to humans and animals. In this study, we investigated the microbiomes of Haemaphysalis longicornis according to sex and life stages. The Shannon index was significantly higher for nymphs than adult ticks. Principal coordinates analysis showed that the microbiome composition of female adult and male adult ticks were different. Notably, Coxiella-like bacterium (AB001519), known as a tick symbiont, was found in all nymphs and female adult ticks, but only one out of 4 male adult ticks had Coxiella-like bacterium (AB001519). In addition, Rickettsia rickettsii, Coxiella burnetii, and Anaplasma bovis were detected in this study.

BACKGROUND: Infectious conditions may increase the risk of venous thromboembolism. The purpose of this study was to evaluate the risk factor for combined infectious disease and its influence on mortality in patients with pulmonary embolism (PE).METHODS: Patients with PE diagnosed based on spiral computed tomography findings of the chest were retrospectively analyzed. They were classified into two groups: patients who developed PE in the setting of infectious disease or those with PE without infection based on review of their medical charts.RESULTS: Of 258 patients with PE, 67 (25.9%) were considered as having PE combined with infectious disease. The sites of infections were the respiratory tract in 52 patients (77.6%), genitourinary tract in three patients (4.5%), and hepatobiliary tract in three patients (4.5%). Underlying lung disease (odds ratio [OR], 3.69; 95% confidence interval [CI], 1.926–7.081; p<0.001), bed-ridden state (OR, 2.84; 95% CI, 1.390–5.811; p=0.004), and malignant disease (OR, 1.867; 95% CI, 1.017–3.425; p=0.044) were associated with combined infectious disease in patients with PE. In-hospital mortality was higher in patients with PE combined with infectious disease than in those with PE without infection (24.6% vs. 11.0%, p=0.006). In the multivariate analysis, combined infectious disease (OR, 4.189; 95% CI, 1.692–10.372; p=0.002) were associated with non-survivors in patients with PE.CONCLUSION: A substantial portion of patients with PE has concomitant infectious disease and it may contribute a mortality in patients with PE.

BACKGROUND: Infectious conditions may increase the risk of venous thromboembolism. The purpose of this study was to evaluate the risk factor for combined infectious disease and its influence on mortality in patients with pulmonary embolism (PE). METHODS: Patients with PE diagnosed based on spiral computed tomography findings of the chest were retrospectively analyzed. They were classified into two groups: patients who developed PE in the setting of infectious disease or those with PE without infection based on review of their medical charts. RESULTS: Of 258 patients with PE, 67 (25.9%) were considered as having PE combined with infectious disease. The sites of infections were the respiratory tract in 52 patients (77.6%), genitourinary tract in three patients (4.5%), and hepatobiliary tract in three patients (4.5%). Underlying lung disease (odds ratio [OR], 3.69; 95% confidence interval [CI], 1.926–7.081; p<0.001), bed-ridden state (OR, 2.84; 95% CI, 1.390–5.811; p=0.004), and malignant disease (OR, 1.867; 95% CI, 1.017–3.425; p=0.044) were associated with combined infectious disease in patients with PE. In-hospital mortality was higher in patients with PE combined with infectious disease than in those with PE without infection (24.6% vs. 11.0%, p=0.006). In the multivariate analysis, combined infectious disease (OR, 4.189; 95% CI, 1.692–10.372; p=0.002) were associated with non-survivors in patients with PE. CONCLUSION A substantial portion of patients with PE has concomitant infectious disease and it may contribute a mortality in patients with PE.

Background: There are sparse data on the utilization rate of implantable cardioverterdefibrillator (ICD) and its beneficial effects in Korean patients with heart failure with reduced left ventricular ejection fraction (LVEF). Methods: Among 5,625 acute heart failure (AHF) patients from 10 tertiary university hospitals across Korea, 485 patients with reassessed LVEF ≤ 35% at least 3 months after the index admission were enrolled in this study. The ICD implantation during the follow-up was evaluated. Mortality was compared between patients with ICDs and age-, sex-, and follow-up duration matched control patients. Results: Among 485 patients potentially indicated for an ICD for primary prevention, only 56 patients (11.5%) underwent ICD implantation during the follow-up. Patients with ICD showed a significantly lower all-cause mortality compared with their matched control population: adjusted hazard ratio (HR) (95% confidence interval [CI]) = 0.39 (0.16–0.92), P = 0.032. The mortality rate was still lower in the ICD group after excluding patients with cardiac resynchronization therapy (adjusted HR [95% CI] = 0.09 [0.01–0.63], P = 0.015).According to the subgroup analysis for ischemic heart failure, there was a significantly lower all-cause mortality in the ICD group than in the no-ICD group (HR [95% CI] = 0.20 [0.06– 0.72], P = 0.013), with a borderline statistical significance (interaction P = 0.069). Conclusion Follow-up data of this large, multicenter registry suggests a significant underutilization of ICD in Korean heart failure patients with reduced LVEF. Survival analysis implies that previously proven survival benefit of ICD in clinical trials could be extrapolated to Korean patients.

OBJECTIVES: The aim of this study was to investigate the association of plasma levels of inflammatory cytokines with dementia and mild cognitive impairment.METHODS: We compared serum levels of tumor necrosis factor-alpha(TNF-alpha), interleukin-6(IL-6), and insulin-like growth factor-1(IGF-I) in patients with dementia(n=8), mild cognitive impairment(MCI, n=15) and normal elderly (n=14). The diagnosis of dementia was made by the Diagnostic Statistical Manual of Mental Disorders-4th edition (DSM-IV). MCI was diagnosed based on the criteria of the National Institute of Aging and Alzheimer Association(NIA-AA) working group.RESULTS: When compared with normal controls, the levels of TNF-alpha and IL-6 were increased and level of IGF-I was decreased in MCI and dementia. Higher levels of TNF-alpha and IL-6 and lower level of IGF-I were also associated with increased age. However, when adjusted for age, the association between diagnosis and TNF-alpha, Il-6 and IGF-I was not significant.CONCLUSION: The difference in plasma levels of inflammatory cytokines in dementia and MCI may be associated with aging.
Aged ; Aging ; Cytokines ; Dementia ; Diagnosis ; Humans ; Insulin-Like Growth Factor I ; Interleukin-6 ; Mild Cognitive Impairment ; Necrosis ; Plasma ; Tumor Necrosis Factor-alpha

BACKGROUND: Chronic obstructive pulmonary disease (COPD) may cause changes in the shape of the thoracic cage by increasing lung volume and hyperinflation. This study investigated changes in thoracic cage dimensions and related factors in patients with COPD. METHODS: We enrolled 85 patients with COPD (76 males, 9 females; mean age, 70.6±7.1 years) and 30 normal controls. Thoracic cage dimensions were measured using chest computed tomography at levels 3, 6, and 9 of the thoracic spine. We measured the maximal transverse diameter, mid-sagittal anteroposterior (AP) diameter, and maximal AP diameter of the right and left hemithorax. RESULTS: The average AP diameter was significantly greater in patients with COPD compared with normal controls (13.1±2.8 cm vs. 12.2±1.13 cm, respectively; p=0.001). The ratio of AP/transverse diameter of the thoracic cage was also significantly greater in patients with COPD compared with normal controls (0.66±0.061 vs. 0.61±0.86; p=0.002). In COPD patients, the AP diameter of the thoracic cage was positively correlated with body mass index (BMI) and 6-minute walk test distance (r=0.395, p<0.001 and r=0.238, p=0.028) and negatively correlated with increasing age (r=−0.231, p=0.034). Multiple regression analysis revealed independent correlation only between BMI and increased ratio of AP/transverse diameter of the thoracic cage (p<0.001). CONCLUSION: Patients with COPD exhibited an increased AP diameter of the thoracic cage compared with normal controls. BMI was associated with increased AP diameter in these patients.
Body Mass Index ; Female ; Humans ; Lung ; Male ; Pulmonary Disease, Chronic Obstructive* ; Spine ; Thorax ; Tomography, X-Ray Computed