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.

Despite the various medications used in clinics, the efforts to develop more effective treatments for depression continue to increase in the past decades mainly because of the treatment-resistant population, and the testing of several hypotheses- and target-based treatments. Undesirable side effects and unresponsiveness to current medications fuel the drive to solve this top global health problem. In this study, we focused on neuroinflammatory response-mediated depression which represents a cluster of depression etiology both in animal models and humans. Several meta-analyses reported that proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were increased in major depressive disorder patients. Inflammatory mediators implicated in depression include type-I interferon and inflammasome pathways. To elucidate the molecular mechanisms of neuroinflammatory cascades underlying the pathophysiology of depression, we introduced hycanthone, an antischistosomal drug, to check whether it can counteract depressive-like behaviors in vivo and normalize the inflammation-induced changes in vitro. Lipopolysaccharide (LPS) treatment increased proinflammatory cytokine expression in the murine microglial cells as well as the stimulation of type I interferon-related pathways that are directly or indirectly regulated by Janus kinase-signal transducer and activator of transcription (JAK-STAT) activation. Hycanthone treatment attenuated those changes possibly by inhibiting the JAK-STAT pathway and inflammasome activation. Hycanthone also ameliorated depressive-like behaviors by LPS. Taken together, we suggest that the inhibitory action of hycanthone against the interferon pathway leading to attenuation of depressive-like behaviors can be a novel therapeutic mechanism for treating depression.

Central venous stenosis is a relatively common complication in hemodialysis patients; however, jugular venous reflux (JVR) and increased intracranial pressure are rare, and associated progressive visual disturbance was reported in only a few cases. Here, we report a case of JVR with visual disturbance and increased intracranial pressure. Notably, the MRI was accompanied by a dilatation of the superior ophthalmic vein, which was mistaken for a cavernous sinus dural arteriovenous fistula (CSdAVF). The patient had JVR on time-of-flight MR angiography (TOF-MRA) and severe stenosis of the left brachiocephalic vein on conventional angiography. After balloon angioplasty for central venous stenosis, he was discharged after improvement of his visual disturbance. Although JVR due to central venous stenosis and CSdAVF might show similar symptoms, treatment plans are different. Therefore, it is important to distinguish radiologically based on a thorough review of MRI and TOF-MRA and confirm the central venous stenosis on cerebral angiography for the accurate diagnosis.

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.

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.

Objectives: The Korea Centers for Disease Control and Prevention has published “A Guideline for Unknown Disease Outbreaks (UDO).” The aim of this report was to introduce tabletop exercises (TTX) to prepare for UDO in the future. Methods: The UDO Laboratory Analyses Task Force in Korea Centers for Disease Control and Prevention in April 2018, assigned unknown diseases into 5 syndromes, designed an algorithm for diagnosis, and made a panel list for diagnosis by exclusion. Using the guidelines and laboratory analyses for UDO, TTX were introduced. Results: Since September 9th , 2018, the UDO Laboratory Analyses Task Force has been preparing TTX based on a scenario of an outbreak caused by a novel coronavirus. In December 2019, through TTX, individual missions, epidemiological investigations, sample treatments, diagnosis by exclusions, and next generation sequencing analysis were discussed, and a novel coronavirus was identified as the causal pathogen. Conclusion Guideline and laboratory analyses for UDO successfully applied in TTX. Conclusions drawn from TTX could be applied effectively in the analyses for the initial response to COVID-19, an ongoing epidemic of 2019 - 2020. Therefore, TTX should continuously be conducted for the response and preparation against UDO.

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.

ymptoms of Parkinson’s disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential. Traditional rating scales previously used in the evaluation of animal spontaneous behavior were insufficient due to factors related to subjectivity and passivity. Thus, experimentally designed applications for an appropriate apparatus are necessary. In this study, we aimed to longitudinally assess hand dexterity function using hand dexterity task (HDT) in NHP-PD models. To validate this assessment, we analyzed the alteration in Parkinsonian tremor signs and the functionality of presynaptic dopaminergic neuron using positron emission tomography imaging of dopamine transporters in these models. In addition, a significant inverse correlation between HDT and DAT level was identified, but no local bias was found. The correlation with intention tremor signs was lower than the resting tremor. In conclusion, the evaluation of HDT may reflect behavioral symptoms of NHP-PD models. Furthermore, HDT was effectively used to experimentally distinguish intention tremors from other tremors.

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

Chronic cough is common in the community and causes significant morbidity. Several factors may underlie this problem, but comorbid conditions located at sensory nerve endings that regulate the cough reflex, including rhinitis, rhinosinusitis, asthma, eosinophilic bronchitis, and gastroesophageal reflux disease, are considered important. However, chronic cough is frequently non-specific and accompanied by not easily identifiable causes during the initial evaluation. Therefore, there are unmet needs for developing empirical treatment and practical diagnostic approaches that can be applied in primary clinics. Meanwhile, in referral clinics, a considerable proportion of adult patients with chronic cough are unexplained or refractory to conventional treatment. The present clinical practice guidelines aim to address major clinical questions regarding empirical treatment, practical diagnostic tools for non-specific chronic cough, and available therapeutic options for chronic wet cough in children and unexplained chronic cough in adults in Korea.
Adult* ; Asthma ; Bronchitis ; Child* ; Cough* ; Eosinophils ; Evidence-Based Medicine ; Gastroesophageal Reflux ; Humans ; Korea* ; Referral and Consultation ; Reflex ; Rhinitis ; Sensory Receptor Cells