1.Effects of Interleukin-17A on the Early Stages of Arterial Thrombosis in Mice
Youngseon PARK ; Yeseul SHIM ; Il KWON ; Heow Won LEE ; Hyo Suk NAM ; Hyun-Jung CHOI ; Ji Hoe HEO
Yonsei Medical Journal 2022;63(7):632-639
Purpose:
Interleukin (IL)-17A has been suggested to play a role in the growth and organization of thrombi. We examined whether IL-17A plays a role in the early stages of thrombosis and whether there are sex differences in the effects of IL-17A.
Materials and Methods:
We performed a blinded, randomized, placebo-controlled study to compare time to thrombotic occlusion and sex differences therein between mice treated with IL-17A and those treated with saline using a ferric chloride-induced model. We also assessed thrombus histology, blood coagulation, and plasma levels of coagulation factors.
Results:
Time to occlusion values did not differ between the IL-17A group and the control group (94.6±86.9 sec vs. 121.0±84.4 sec, p=0.238). However, it was significantly shorter in the IL-17A group of female mice (74.6±57.2 sec vs. 130.0±76.2 sec, p=0.032). In rotational thromboelastometry, the IL-17A group exhibited increased maximum clot firmness (71.3±4.5 mm vs. 66.7±4.7 mm, p=0.038) and greater amplitude at 30 min (69.7±5.2 mm vs. 64.5±5.3 mm, p=0.040) than the control group. In Western blotting, the IL-17A group showed higher levels of coagulation factor XIII (2.2±1.5 vs. 1.0±0.9, p=0.008), monocyte chemoattractant protein-1 (1.6±0.6 vs. 1.0±0.4, p=0.023), and tissue factor (1.5±0.6 vs. 1.0±0.5, p=0.003).
Conclusion
IL-17A plays a role in the initial st ages of arterial thrombosis in mice. Coagulation factors and monocyte chemoattractant protein-1 may be associated with IL-17A-mediated thrombosis.
2.The Application of a Dried Balanced Heparin Syringe Can Attenuate the Dilution Effect in Rapid Point-of-care Potassium Testing for the Early Identification of Hyperkalemia in the Emergency Department.
Min Kyung SEUNG ; Sung Phil CHUNG ; Yoo Seok PARK ; Hyun Soo CHUNG ; Hye Sun LEE ; Youngseon JOO ; Je Sung YOU ; Incheol PARK
Journal of the Korean Society of Emergency Medicine 2015;26(6):509-516
PURPOSE: Current methods to evaluate the blood concentration of potassium (K) on point-of-care (POC) are influenced by the relative volumes of heparin and arterial blood. Blood potassium concentration may be underestimated with a high volume of heparin or low volume of blood. This dilution effect can produce false negative results that negatively affect decision-making of clinicians and throw critical patients into crisis. We hypothesized that the application of a dried balanced heparin syringe in rapid POC-K+ could attenuate the dilution effect and would more accurately and consistently measure the concentration of potassium compared with reference testing in emergency situations. METHODS: This retrospective study was conducted between January, 1, 2008 and September, 30, 2013 at an urban hospital affiliated with our institution. To attenuate the dilution effect, dried balanced heparin syringes (HS) were also used between October, 1, 2011 and September, 30, 2013. Concentrations of potassium were compared between the dried balanced HS group and the liquid HS group. The reliability of each of these outcome measures was assessed using intra-class correlation coefficient analysis. RESULTS: Application of dried balanced HS improved the degree of concordance for potassium using two different assays. The false negative rate was significantly improved from 9.1% (95% CI 7.3-11.0) to 5.7% (95% CI 3.5-8.0) in the dried balanced HS group compared with the liquid HS liquid group (p=0.037). CONCLUSION: This study suggests that the usage of dried balanced HS could attenuate the dilution effect in rapid POC-K+ and predict potassium levels more accurately for identification of patients at risk of hyperkalemia in emergency situations.
Emergencies*
;
Emergency Service, Hospital*
;
Heparin*
;
Hospitals, Urban
;
Humans
;
Hyperkalemia*
;
Outcome Assessment (Health Care)
;
Potassium*
;
Resuscitation
;
Retrospective Studies
;
Syringes*
3.Evaluating the Utility of Rapid Point-of-Care Potassium Testing for the Early Identification of Hyperkalemia in Patients with Chronic Kidney Disease in the Emergency Department.
Je Sung YOU ; Yoo Seok PARK ; Hyun Soo CHUNG ; Hye Sun LEE ; Youngseon JOO ; Jong Woo PARK ; Sung Phil CHUNG ; Shin Ho LEE ; Hahn Shick LEE
Yonsei Medical Journal 2014;55(5):1348-1353
PURPOSE: Severe hyperkalemia leads to significant morbidity and mortality if it is not immediately recognized and treated. The concentration of potassium (K+) in the serum increases along with deteriorating renal function. The use of point-of-care K+ (POC-K+) in chronic kidney disease (CKD) could reduce the time for an accurate diagnosis and treatment, saving lives. We hypothesized that POC-K+ would accurately report K+ serum level without significant differences compared to reference testing, regardless of the renal function of the patient. MATERIALS AND METHODS: The retrospective study was performed between January 2008 and September 2011 at an urban hospital in Seoul. The screening program using POC was conducted as a critical pathway for rapid evaluation and treatment of hyperkalemia since 2008. When a patient with CKD had at least one warning symptom or sign of hyperkalemia, both POC-K+ and routine laboratory tests were simultaneously ordered. The reliability of the two assays for serum-creatinine was assessed by intra-class correlation coefficient (ICC) analysis using absolute agreement of two-way mixed model. RESULTS: High levels of reliability were found between POC and the laboratory reference tests for K+ (ICC=0.913, 95% CI 0.903-0.922) and between two tests for K+ according to changes in the serum-creatinine levels in CKD patients. CONCLUSION: The results of POC-K+ correlate well with values obtained from reference laboratory tests and coincide with changes in serum-creatinine of patients with CKD.
Blood Chemical Analysis/methods
;
Emergency Service, Hospital
;
Humans
;
Hyperkalemia/*diagnosis
;
Point-of-Care Systems
;
Potassium/*blood
;
Renal Insufficiency, Chronic/*blood
;
Reproducibility of Results
;
Retrospective Studies
;
Sensitivity and Specificity
4.The Clinical Characteristics for Emergency Endotracheal Intubation in Acute Drug Intoxication.
Eol HAN ; Hyun Soo CHUNG ; Yoo Seok PARK ; Je Sung YOU ; Youngseon JOO ; Taeyoung KONG ; Incheol PARK ; Sung Phil CHUNG
Journal of The Korean Society of Clinical Toxicology 2015;13(1):11-18
PURPOSE: The aim of this study was to compare the clinical characteristics in emergency endotracheal intubation between patients with acute drug intoxication and medical disease. METHODS: Data for airway registry collected in two emergency departments (ED) between April 2006 and March 2010 were reviewed retrospectively. The airway registry data included patient's demographic information and variables such as Cormack-Lehane grade, 3-3-2 finger analysis, success rate, the number of attempts at intubation, complications of intubation, and clinical outcomes after intubation. RESULTS: A total of 1480 patients were enrolled; 62 patients were classified as belonging to the intubation group after the drug intoxication group. No significant differences in Cormack-Lehane grade, 3-3-2 finger analysis, success rate, the number of attempts at intubation, and complications after intubation were observed between patients with acute drug intoxication and medical disease. However, significant difference was observed for indication of emergency endotracheal intubation. While emergency endotracheal intubations were usually performed in medical patients because of failure of airway patency, they were performed in intoxicated patients with the goal of preventing serious complications. CONCLUSION: Anatomical structures related to endotracheal intubation, the process and clinical outcome of intoxicated patients are not significantly different from those for medical patients.
Emergencies*
;
Emergency Service, Hospital
;
Fingers
;
Humans
;
Intubation
;
Intubation, Intratracheal*
;
Poisoning
;
Retrospective Studies
5.Characterization of Ferric Chloride-Induced Arterial Thrombosis Model of Mice and the Role of Red Blood Cells in Thrombosis Acceleration
Yeseul SHIM ; Il KWON ; Youngseon PARK ; Heow Won LEE ; Jayoung KIM ; Young Dae KIM ; Hyo Suk NAM ; Sungha PARK ; Ji Hoe HEO
Yonsei Medical Journal 2021;62(11):1032-1041
Purpose:
The ferric chloride (FeCl3)-induced thrombosis model is widely used for thrombosis research. However, it lacks standardization with uncertainty in the exact mechanism of thrombosis. This study aimed to characterize thrombus formation in a mouse model.
Materials and Methods:
We investigated thrombus formation and stability using various FeCl3 concentrations (10%, 20%, 30%, 40%, and 50%, w/v) in carotid arteries of the Institute of Cancer Research (ICR) and C57BL/6N mice using the FeCl3-induced thrombosis model. We also investigated thrombus histopathology using immunohistochemistry and electron microscopy.
Results:
Higher FeCl3 concentrations induced dose-dependent, faster, larger, and more stable thrombus formation in both strains of mice. However, the ICR mice showed better dose-responses in thrombus formation and stability compared to the C57BL/6N mice. Thrombi were fibrin- and platelet-rich without significant changes across FeCl3 concentrations. However, the content of red blood cells (RBCs) increased with increasing FeCl3 concentrations (p for trend <0.001) and inversely correlated with time to occlusion (r=-0.65, p<0.001). While platelets and fibrin were evenly distributed over the thrombus, RBCs were predominantly located near the FeCl3 treatment area. Transmission electron microscopy showed that RBCs attached to and were surrounded by aggregates of degranulated platelets, suggesting their potential role in platelet activation.
Conclusion
Faster and larger thrombus formation is induced in a dose-dependent manner by a wide range of FeCl3 concentrations, but the stable thrombus formation requires higher FeCl3 concentrations. Mouse strain affects thrombus formation and stability. RBCs and their interaction with platelets play a key role in the acceleration of FeCl3-induced thrombosis.
6.Characterization of Ferric Chloride-Induced Arterial Thrombosis Model of Mice and the Role of Red Blood Cells in Thrombosis Acceleration
Yeseul SHIM ; Il KWON ; Youngseon PARK ; Heow Won LEE ; Jayoung KIM ; Young Dae KIM ; Hyo Suk NAM ; Sungha PARK ; Ji Hoe HEO
Yonsei Medical Journal 2021;62(11):1032-1041
Purpose:
The ferric chloride (FeCl3)-induced thrombosis model is widely used for thrombosis research. However, it lacks standardization with uncertainty in the exact mechanism of thrombosis. This study aimed to characterize thrombus formation in a mouse model.
Materials and Methods:
We investigated thrombus formation and stability using various FeCl3 concentrations (10%, 20%, 30%, 40%, and 50%, w/v) in carotid arteries of the Institute of Cancer Research (ICR) and C57BL/6N mice using the FeCl3-induced thrombosis model. We also investigated thrombus histopathology using immunohistochemistry and electron microscopy.
Results:
Higher FeCl3 concentrations induced dose-dependent, faster, larger, and more stable thrombus formation in both strains of mice. However, the ICR mice showed better dose-responses in thrombus formation and stability compared to the C57BL/6N mice. Thrombi were fibrin- and platelet-rich without significant changes across FeCl3 concentrations. However, the content of red blood cells (RBCs) increased with increasing FeCl3 concentrations (p for trend <0.001) and inversely correlated with time to occlusion (r=-0.65, p<0.001). While platelets and fibrin were evenly distributed over the thrombus, RBCs were predominantly located near the FeCl3 treatment area. Transmission electron microscopy showed that RBCs attached to and were surrounded by aggregates of degranulated platelets, suggesting their potential role in platelet activation.
Conclusion
Faster and larger thrombus formation is induced in a dose-dependent manner by a wide range of FeCl3 concentrations, but the stable thrombus formation requires higher FeCl3 concentrations. Mouse strain affects thrombus formation and stability. RBCs and their interaction with platelets play a key role in the acceleration of FeCl3-induced thrombosis.
7.Usefulness of Serial Measurement of the Platelet Volume Indices to Predict 30-day Mortality in Patients with ST Segment Elevation Myocardial Infarction.
Gina YU ; Je Sung YOU ; Sung Phil CHUNG ; Taeyoung KONG ; Dongryul KO ; Sinae KIM ; Youngseon JOO ; Yoon Jung HWANG ; Minhong CHOA ; Incheol PARK
Journal of the Korean Society of Emergency Medicine 2017;28(5):514-525
PURPOSE: Among the survivors of a ST elevation myocardial infarction (STEMI), higher platelet volume indices (mean platelet volume, MPV; platelet distribution width, PDW) are associated with impaired reperfusion and ventricular dysfunction. This study examined the relationship between the platelet volume indices and 30-day mortality with STEMI patients who underwent primary percutaneous coronary intervention (PCI). METHODS: This retrospective cohort study included patients presenting to the emergency department with STEMI between January 2011 and May 2016. The platelet volume indices were measured serially, using an automatic hematology analyzer, from admission to 24 hours after admission. The prognostic value of MPV, PDW for the 30-day mortality was determined by Cox proportional hazards model analysis. RESULTS: A total of 608 STEMI patients, who underwent reperfusion, were enrolled in this study. According to the multivariable Cox proportional hazard model, higher MPV (hazard ratio [HR], 1.414; 95% confidence interval [CI], 1.024-1.953; p=0.035) and PDW (HR, 1.043; 95% CI, 1.006-1.083; p=0.024) values at time-24 (24 hours after admission) were significant risk factors for the 30-day mortality. A MPV value >8.6 fL (HR, 5.953; 95% CI, 2.973-11.918; p<0.001) and PDW value >56.1% (HR, 5.117; 95% CI, 2.640-9.918; p<0.001) at time-24 were associated with an increased risk of 30-day mortality. CONCLUSION: The platelet volume indices without an additional burden of cost or time, can be measured rapidly and simply. Higher MPV and PDW levels predict independently the 30-day mortality in patients with STEMI after PCI.
Blood Platelets*
;
Cohort Studies
;
Emergency Service, Hospital
;
Hematology
;
Humans
;
Mean Platelet Volume
;
Mortality*
;
Myocardial Infarction*
;
Percutaneous Coronary Intervention
;
Platelet Activation
;
Prognosis
;
Proportional Hazards Models
;
Reperfusion
;
Retrospective Studies
;
Risk Factors
;
Survivors
;
Ventricular Dysfunction
8.Usefulness of Delta Neutrophil Index to Predict 30-day Mortality in Patients with Mechanical Bowel Obstruction.
Sehee HAN ; Je Sung YOU ; Sung Phil CHUNG ; Hye Sun LEE ; Taeyoung KONG ; Ji Hoon KIM ; Dongryul KO ; Youngseon JOO ; Minhong CHOA ; Incheol PARK
Journal of the Korean Society of Emergency Medicine 2017;28(5):403-412
PURPOSE: Mechanical bowel obstruction (MBO) is a common emergency problem resulting in high morbidity and mortality. The delta neutrophil index (DNI), reflecting the fraction of circulating immature granulocytes, is associated with increased mortality in patients with infection and/or systemic inflammation. This study was conducted to investigate the relationship between DNI and 30-day mortality in patients with MBO. METHODS: We retrospectively identified consecutive patients (>18 years old) with MBO admitted to the emergency department from January 1, 2013 to April 30, 2015. The diagnosis of MBO was confirmed using clinical and radiological findings. The DNI was determined on each day of hospitalization. The outcome of interest was the 30-day mortality and the prognostic value of DNI for 30-day mortality was ascertained by Cox proportional hazards model analysis. RESULTS: A total of 518 patients with MBO were included in this study. According to multivariate Cox proportional hazard models, higher DNI at admission (hazard ratio [HR], 1.080; 95% confidence interval [CI], 1.036-1.126; p<0.001) was a strong independent predictor of short-term mortality. Among patients with MBO, a DNI >1.9% on admission (HR, 9.410; 95% CI, 2.671-33.145; p<0.001) was associated with increased 30-day mortality. Furthermore, the accuracy of DNI for predicting 30-day mortality was superior to that of other parameters. CONCLUSION: The DNI can be measured rapidly and simply on emergency department admission without additional cost or time burden. Increased DNI values are associated with 30-day mortality in patients with MBO.
Diagnosis
;
Emergencies
;
Emergency Service, Hospital
;
Granulocytes
;
Hospitalization
;
Humans
;
Inflammation
;
Mortality*
;
Neutrophils*
;
Proportional Hazards Models
;
Retrospective Studies
9.Primary Tumor Suppression and Systemic Immune Activation of Macrophages through the Sting Pathway in Metastatic Skin Tumor
Chun-Bong SYNN ; Dong Kwon KIM ; Jae Hwan KIM ; Youngseon BYEON ; Young Seob KIM ; Mi Ran YUN ; Ji Min LEE ; Wongeun LEE ; Eun Ji LEE ; Seul LEE ; You-Won LEE ; Doo Jae LEE ; Hyun-Woo KIM ; Chang Gon KIM ; Min Hee HONG ; June Dong PARK ; Sun Min LIM ; Kyoung-Ho PYO
Yonsei Medical Journal 2022;63(1):42-55
Purpose:
Agonists of the stimulator of interferon genes (STING) play a key role in activating the STING pathway by promoting the production of cytokines. In this study, we investigated the antitumor effects and activation of the systemic immune response of treatment with DMXAA (5,6-dimethylxanthenone-4-acetic acid), a STING agonist, in EML4-ALK lung cancer and CT26 colon cancer.
Materials and Methods:
The abscopal effects of DMXAA in the treatment of metastatic skin nodules were assessed. EML4-ALK lung cancer and CT26 colon cancer models were used to evaluate these effects after DMXAA treatment. To evaluate the expression of macrophages and T cells, we sacrificed the tumor-bearing mice after DMXAA treatment and obtained the formalin-fixed paraffin-embedded (FFPE) tissue and tumor cells. Immunohistochemistry and flow cytometry were performed to analyze the expression of each FFPE and tumor cell.
Results:
We observed that highly infiltrating immune cells downstream of the STING pathway had increased levels of chemokines after DMXAA treatment. In addition, the levels of CD80 and CD86 in antigen-presenting cells were significantly increased after STING activation. Furthermore, innate immune activation altered the systemic T cell-mediated immune responses, induced proliferation of macrophages, inhibited tumor growth, and increased numbers of cytotoxic memory T cells. Tumor-specific lymphocytes also increased in number after treatment with DMXAA.
Conclusion
The abscopal effect of DMXAA treatment on the skin strongly reduced the spread of EML4-ALK lung cancer and CT26 colon cancer through the STING pathway and induced the presentation of antigens.