Early identification of suspected serious infection among patients afebrile at initial presentation using neural network models and natural language processing: A development and external validation study in the emergency department.

OBJECTIVE: To develop and externally validate models based on neural networks and natural language processing (NLP) to identify suspected serious infections in emergency department (ED) patients afebrile at initial presentation. METHODS: This retrospective study included adults who visited the ED afebrile at initial presentation. We developed four models based on artificial neural networks to identify suspected serious infection. Patient demographics, vital signs, laboratory test results and information extracted from initial ED physician notes using term frequency-inverse document frequency were used as model variables. Models were trained and internally validated with data from one hospital and externally validated using data from a different hospital. Model discrimination was evaluated using area under the receiver operating characteristic curve (AUC) and 95% confidence intervals (CIs). RESULTS: The training, internal validation, and external validation datasets comprised 150,699, 37,675, and 85,098 patients, respectively. The AUCs (95% CIs) for Models 1 (demographics + vital signs), 2 (demographics + vital signs + initial ED physician note), 3 (demographics + vital signs + laboratory tests), and 4 (demographics + vital signs + laboratory tests + initial ED physician note) in the internal validation dataset were 0.789 (0.782-0.796), 0.867 (0.862-0.872), 0.881 (0.876-0.887), and 0.911 (0.906-0.915), respectively. In the external validation dataset, the AUCs (95% CIs) of Models 1, 2, 3, and 4 were 0.824 (0.817-0.830), 0.895 (0.890-0.899), 0.879 (0.873-0.884), and 0.913 (0.909-0.917), respectively. Model 1 can be utilized immediately after ED triage, Model 2 can be utilized after the initial physician notes are recorded (median time from ED triage: 28 min), and Models 3 and 4 can be utilized after the initial laboratory tests are reported (median time from ED triage: 68 min). CONCLUSIONS: We developed and validated models to identify suspected serious infection in the ED. Extracted information from initial ED physician notes using NLP contributed to increased model performance, permitting identification of suspected serious infection at early stages of ED visits.

Measurement of level of consciousness by AVPU scale assessment system based on automated video and speech recognition technology.

OBJECTIVE: To develop an alert/verbal/painful/unresponsive (AVPU) scale assessment system based on automated video and speech recognition technology (AVPU-AVSR) that can automatically assess a patient's level of consciousness and evaluate its performance through clinical simulation. METHODS: We developed an AVPU-AVSR system with a whole-body camera, face camera, and microphone. The AVPU-AVSR system automatically extracted essential audiovisual features to assess the AVPU score from the recorded video files. Arm movement, pain stimulus, and eyes-open state were extracted using a rule-based approach using landmarks estimated from pre-trained pose and face estimation models. Verbal stimuli were extracted using a pre-trained speech-recognition model. Simulations of a physician examining the consciousness of 12 simulated patients for 16 simulation scenarios (4 for each of "Alert", "Verbal", "Painful", and "Unresponsive") were conducted under the AVPU-AVSR system. The accuracy, sensitivity, and specificity of the AVPU-AVSR system were assessed. RESULTS: A total of 192 cases with 12 simulated patients were assessed using the AVPU-AVSR system with a multi-class accuracy of 0.95 (95% confidence interval [CI] (0.92-0.98). The sensitivity and specificity (95% CIs) for detecting impaired consciousness were 1.00 (0.97-1.00) and 0.88 (0.75-0.95), respectively. The sensitivity and specificity of each extracted feature ranged from 0.88 to 1.00 and 0.98 to 1.00. CONCLUSIONS: The AVPU-AVSR system showed good accuracy in assessing consciousness levels in a clinical simulation and has the potential to be implemented in clinical practice to automatically assess mental status.

ETV2 Enhances CXCL5 Secretion from Endothelial Cells, Leading to the Promotion of Vascular Smooth Muscle Cell Migration.

Abnormal communication between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) promotes vascular diseases, including atherogenesis. ETS variant transcription factor 2 (ETV2) plays a substantial role in pathological angiogenesis and the reprogramming of ECs; however, the role of ETV2 in the communication between ECs and VSMCs has not been revealed. To investigate the interactive role of ETV2 in the EC to VSMC phenotype, we first showed that treatment with a conditioned medium from ETV2-overexpressed ECs (Ad-ETV2 CM) significantly increased VSMC migration. The cytokine array showed altered levels of several cytokines in Ad-ETV2 CM compared with those in normal CM. We found that C-X-C motif chemokine 5 (CXCL5) promoted VSMC migration using the Boyden chamber and wound healing assays. In addition, an inhibitor of C-X-C motif chemokine receptor 2 (CXCR2) (the receptor for CXCL5) significantly inhibited this process. Gelatin zymography showed that the activities of matrix metalloproteinase (MMP)-2 and MMP-9 increased in the media of VSMCs treated with Ad-ETV2 CM. Western blotting revealed a positive correlation between Akt/p38/c-Jun phosphorylation and CXCL5 concentration. The inhibition of Akt and p38-c-Jun effectively blocked CXCL5-induced VSMC migration. In conclusion, CXCL5 from ECs induced by ETV2 promotes VSMC migration via MMP upregulation and the activation of Akt and p38/c-Jun.

Oxidative stress generated by polycyclic aromatic hydrocarbons from ambient particulate matter enhance vascular smooth muscle cell migration through MMP upregulation and actin reorganization.

BACKGROUND: Epidemiological studies have suggested that elevated concentrations of particulate matter (PM) are strongly associated with the incidence of atherosclerosis, however, the underlying cellular and molecular mechanisms of atherosclerosis by PM exposure and the components that are mainly responsible for this adverse effect remain to be established. In this investigation, we evaluated the effects of ambient PM on vascular smooth muscle cell (VSMC) behavior. Furthermore, the effects of polycyclic aromatic hydrocarbons (PAHs), major components of PM, on VSMC migration and the underlying mechanisms were examined. RESULTS: VSMC migration was significantly increased by treatment with organic matters extracted from ambient PM. The total amount of PAHs contained in WPM was higher than that in SPM, leading to higher ROS generation and VSMC migration. The increased migration was successfully inhibited by treatment with the anti-oxidant, N-acetyl-cysteine (NAC). The levels of matrix metalloproteinase (MMP) 2 and 9 were significantly increased in ambient PM-treated VSMCs, with MMP9 levels being significantly higher in WPM-treated VSMCs than in those treated with SPM. As expected, migration was significantly increased in all tested PAHs (anthracene, ANT; benz(a)anthracene, BaA) and their oxygenated derivatives (9,10-Anthraquinone, AQ; 7,12-benz(a)anthraquinone, BAQ, respectively). The phosphorylated levels of focal adhesion kinase (FAK) and formation of the focal adhesion complex were significantly increased in ambient PM or PAH-treated VSMCs, and these effects were blocked by administration of NAC or α-NF, an inhibitor of AhR, the receptor that allows PAH uptake. Subsequently, the levels of phosphorylated Src and NRF, the downstream targets of FAK, were altered with a pattern similar to that of p-FAK. CONCLUSIONS: PAHs, including oxy-PAHs, in ambient PM may have dual effects that lead to an increase in VSMC migration. One is the generation of oxidative stress followed by MMP upregulation, and the other is actin reorganization that results from the activation of the focal adhesion complex.

Machine Learning Analysis to Identify Data Entry Errors in Prehospital Patient Care Reports: A Case Study of a National Out-of-Hospital Cardiac Arrest Registry.

Background: The objective of this study was to develop and validate machine learning models for data entry error detection in a national out-of-hospital cardiac arrest (OHCA) prehospital patient care report database.Methods: Adult OHCAs of presumed cardiac etiology were included. Data entry errors were defined as discrepancies between the coded data and the free-text note documenting the intervention or event; for example, information that was recorded as "absent" in the coded data but "present" in the free-text note. Machine learning models using the extreme gradient boosting, logistic regression, extreme gradient boosting outlier detection, and K-nearest neighbor outlier detection algorithms for error detection within nine core variables were developed and then validated for each variable.Results: Among 12,100 OHCAs, the proportion of cases with at least one error type was 16.2%. The area under the receiver operating characteristic curve (AUC) of the best-performing model (model with the highest AUC for each outcome variable) was 0.71-0.95. Machine learning models detected errors most efficiently for outcome place and initial rhythm errors; 82.6% of place errors and 93.8% of initial rhythm errors could be detected while checking 11 and 35% of data, respectively, compared to the strategy of checking all data.Conclusion: Machine learning models can detect data entry errors in care reports of emergency medical services (EMS) clinicians with acceptable performance and likely can improve the efficiency of the process of data quality control. EMS organizations that provide more prehospital interventions for OHCA patients could have higher error rates and may benefit from the adoption of error-detection models.

Prediction of bacteremia at the emergency department during triage and disposition stages using machine learning models.

INTRODUCTION: Bacteremia is a common but critical condition with high mortality that requires timely and optimal treatment in the emergency department (ED). The prediction of bacteremia at the ED during triage and disposition stages could support the clinical decisions of ED physicians regarding the appropriate treatment course and safe ED disposition. This study developed and validated machine learning models to predict bacteremia in the emergency department during triage and disposition stages. METHODS: This study enrolled adult patients who visited a single tertiary hospital from 2016 to 2018 and had at least two sets of blood cultures during their ED stay. Demographic information, chief complaint, triage level, vital signs, and laboratory data were used as model predictors. We developed and validated prediction models using 10 variables at the time of ED triage and 42 variables at the time of disposition. The extreme gradient boosting (XGB) model was compared with the random forest and multivariable logistic regression models. We compared model performance by assessing the area under the receiver operating characteristic curve (AUC), test characteristics, and decision curve analysis. RESULTS: A total of 24,768 patients were included: 16,197 cases were assigned to development, and 8571 cases were assigned to validation. The proportion of bacteremia was 10.9% and 10.4% in the development and validation datasets, respectively. The Triage XGB model (AUC, 0.718; 95% confidence interval (CI), 0.701-0.735) showed acceptable discrimination performance with a sensitivity over 97%. The Disposition XGB model (AUC, 0.853; 95% CI, 0.840-0.866) showed excellent performance and provided the greatest net benefit throughout the range of thresholds probabilities. CONCLUSIONS: The Triage XGB model could be used to identify patients with a low risk of bacteremia immediately after initial ED triage. The Disposition XGB model showed excellent discriminative performance.

Impact of the COVID-19 Outbreak on Trends in Emergency Department Utilization in Children: a Multicenter Retrospective Observational Study in Seoul Metropolitan Area, Korea.

BACKGROUND: Understanding the changes in emergency department (ED) visit patterns during the coronavirus disease 2019 (COVID-19) outbreak is important for effectively operating EDs during the pandemic. We aimed to analyze the changes in pediatric ED visits during the COVID-19 pandemic and examine the relationship between the number of ED visits and the stringency of government social distancing measures. METHODS: This multicenter retrospective study used data of pediatric (age < 18 years) ED visits in Seoul metropolitan area from June 1, 2018, to May 31, 2020. Patient demographics, ED results, and diagnoses were compared during the COVID-19 period and the previous year. To evaluate the effect of the stringency of social distancing measures on the number of ED visits, a Poisson regression model was developed with month, year, and the average monthly Government Response Stringency Index (GRSI) as fixed effects. RESULTS: In total, 190,732 patients were included. The number of pediatric ED visits during the COVID-19 period was 58.1% lower than in the previous year. There were disproportionate decreases in the numbers of ED visits for children in early childhood (66.5%), low-acuity children (55.2-63.8%), those who did not use an ambulance (59.0%), and those visiting the ED for noninjury complaints (64.9%). The proportion of admissions increased from 11.9% to 16.6%. For every 10-point increase in the GRSI, there was a 15.1% decrease in monthly ED visits. CONCLUSION: A striking decrease in pediatric ED visits was observed during the COVID-19 outbreak, the scale which was associated with the stringency of government policies. Changes in the number and characteristics of children visiting the ED should be considered to facilitate the effective operation of EDs during the pandemic.

Clinical Outcomes of Ticagrelor in Korean Patients with Acute Myocardial Infarction without High Bleeding Risk.

BACKGROUND: Although ticagrelor is known to increase the bleeding risk compared to clopidogrel in East Asian patients, its clinical benefits in patients with acute myocardial infarction (AMI) without high bleeding risk (HBR) remains unknown. METHODS: A total of 7,348 patients who underwent successful percutaneous coronary intervention (PCI) from the Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH), between November 2011 and December 2015, were divided into two groups according to the Academic Research Consortium for HBR criteria (KAMIR-HBR, 2,469 patients; KAMIR-non HBR, 4,879 patients). We compared in-hospital major adverse cardiovascular events (MACEs, defined as a composite of cardiac death, non-fatal myocardial infarction, or stroke), and the thrombolysis in myocardial infarction (TIMI) major bleeding between ticagrelor and clopidogrel in the KAMIR-HBR and the KAMIR-non HBR groups, respectively. RESULTS: After propensity score matching, ticagrelor had a higher incidence of in-hospital TIMI major bleeding than clopidogrel in all patients (odds ratio [OR], 1.683; 95% confidence interval [CI], 1.010-2.805; P = 0.046) and the KAMIR-HBR group (OR, 3.460; 95% CI, 1.374-8.714; P = 0.008). However, there was no significant difference in in-hospital TIMI major bleeding between ticagrelor and clopidogrel in the KAMIR-non HBR group (OR, 1.436; 95% CI, 0.722-2.855; P = 0.303). No differences were observed in the cumulative incidences of in-hospital and 6-month MACEs between ticagrelor and clopidogrel in both groups. CONCLUSIONS: The bleeding risk of ticagrelor was attenuated in Korean patients with AMI without HBR. Appropriate patient selection could reduce in-hospital bleeding complications associated with ticagrelor in Korean patients with AMI who underwent successful PCI.

Enhancement in Performance of Septic Shock Prediction Using National Early Warning Score, Initial Triage Information, and Machine Learning Analysis.

BACKGROUND: Several studies reported that the National Early Warning Score (NEWS) has shown superiority over other screening tools in discriminating emergency department (ED) patients who are likely to progress to septic shock. OBJECTIVES: To improve the performance of the NEWS for septic shock prediction by adding variables collected during ED triage, and to implement a machine-learning algorithm. METHODS: The study population comprised adult ED patients with suspected infection. To detect septic shock within 24 h after ED arrival, the Sepsis-3 clinical criteria and nine variables were used: NEWS, age, gender, systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, body temperature, and oxygen saturation. The model was developed using logistic regression (LR), extreme gradient boosting (XGB), and artificial neural network (ANN) algorithms. The evaluations were performed using an area under the receiver operating characteristic curve (AUROC), Hosmer-Lemeshow test, and net reclassification index (NRI). RESULTS: Overall, 41,687 patients were enrolled. The AUROC of the model with NEWS, age, gender, and the six vital signs (0.835-0.845) was better than that of the baseline model (0.804). The XGB model (AUROC 0.845) was the most accurate, compared with LR (0.844) and ANN (0.835). The LR and XGB models were well calibrated; however, the ANN showed poor calibration power. The LR and XGB models showed better reclassification than the baseline model with positive NRI. CONCLUSION: The discrimination power of the model for screening septic shock using NEWS, age, gender, and the six vital signs collected at ED triage outperformed the baseline NEWS model.

LRP5 Regulates HIF-1α Stability via Interaction with PHD2 in Ischemic Myocardium.

Low-density lipoprotein receptor-related protein 5 (LRP5) has been studied as a co-receptor for Wnt/ß-catenin signaling. However, its role in the ischemic myocardium is largely unknown. Here, we show that LRP5 may act as a negative regulator of ischemic heart injury via its interaction with prolyl hydroxylase 2 (PHD2), resulting in hypoxia-inducible factor-1α (HIF-1α) degradation. Overexpression of LRP5 in cardiomyocytes promoted hypoxia-induced apoptotic cell death, whereas LRP5-silenced cardiomyocytes were protected from hypoxic insult. Gene expression analysis (mRNA-seq) demonstrated that overexpression of LRP5 limited the expression of HIF-1α target genes. LRP5 promoted HIF-1α degradation, as evidenced by the increased hydroxylation and shorter stability of HIF-1α under hypoxic conditions through the interaction between LRP5 and PHD2. Moreover, the specific phosphorylation of LRP5 at T1492 and S1503 is responsible for enhancing the hydroxylation activity of PHD2, resulting in HIF-1α degradation, which is independent of Wnt/ß-catenin signaling. Importantly, direct myocardial delivery of adenoviral constructs, silencing LRP5 in vivo, significantly improved cardiac function in infarcted rat hearts, suggesting the potential value of LRP5 as a new target for ischemic injury treatment.

Oxygenated polycyclic aromatic hydrocarbons from ambient particulate matter induce electrophysiological instability in cardiomyocytes.

BACKGROUND: Epidemiologic studies have suggested that elevated concentrations of particulate matter (PM) are strongly associated with an increased risk of developing cardiovascular diseases, including arrhythmia. However, the cellular and molecular mechanisms by which PM exposure causes arrhythmia and the component that is mainly responsible for this adverse effect remains to be established. In this study, the arrhythmogenicity of mobilized organic matter from two different types of PM collected during summer (SPM) and winter (WPM) seasons in the Seoul metropolitan area was evaluated. In addition, differential effects between polycyclic aromatic hydrocarbons (PAHs) and oxygenated PAHs (oxy-PAHs) on the induction of electrophysiological instability were examined. RESULTS: We extracted the bioavailable organic contents of ambient PM, measuring 10 µm or less in diameter, collected from the Seoul metropolitan area using a high-volume air sampler. Significant alterations in all factors tested for association with electrophysiological instability, such as intracellular Ca2+ levels, reactive oxygen species (ROS) generation, and mRNA levels of the Ca2+-regulating proteins, sarcoplasmic reticulum Ca2+ATPase (SERCA2a), Ca2+/calmodulin-dependent protein kinase II (CaMK II), and ryanodine receptor 2 (RyR2) were observed in cardiomyocytes treated with PM. Moreover, the alterations were higher in WPM-treated cardiomyocytes than in SPM-treated cardiomyocytes. Three-fold more oxy-PAH concentrations were observed in WPM than SPM. As expected, electrophysiological instability was induced higher in oxy-PAHs (9,10-anthraquinone, AQ or 7,12-benz(a) anthraquinone, BAQ)-treated cardiomyocytes than in PAHs (anthracene, ANT or benz(a) anthracene, BaA)-treated cardiomyocytes; oxy-PAHs infusion of cells mediated by aryl hydrocarbon receptor (AhR) was faster than PAHs infusion. In addition, ROS formation and expression of calcium-related genes were markedly more altered in cells treated with oxy-PAHs compared to those treated with PAHs. CONCLUSIONS: The concentrations of oxy-PAHs in PM were found to be higher in winter than in summer, which might lead to greater electrophysiological instability through the ROS generation and disruption of calcium regulation.

Epidemiology and Outcomes of Sports-Related Traumatic Brain Injury in Children.

BACKGROUND: Traumatic brain injury (TBI) is one of the leading causes of pediatric disability that results in many emergency department visits. The risk of TBI is high while playing sports. The aim of this study was to examine the demographics and clinical characteristics of sports-related TBI. METHODS: We performed a multicenter observational study using the Emergency Department-Based Injury In-Depth Surveillance database in Korea. Patients aged 5 to 18 years old, who sustained unintentional, sports-related head injuries between January 2011 and December 2016 were included. The type of sports was the main variable of interest, and it was classified into 6 categories. The primary outcome was TBI, and the secondary outcome was intracranial injury and hospital admission. A multivariable logistic regression analysis was performed to calculate the adjusted odds ratios (aORs) with 95% confidence intervals for the outcomes by sports type. RESULTS: Of the 1,537,617 injured patients, 10,717 (0.7%) patients were included in the study. Most of the patients were male (87.5%), and the most prevalent sports type was field sports (51.2%). The proportion of TBI, intracranial injury, and admission were 15.7%, 1.2%, and 3.5%, respectively. The aORs of TBI, intracranial injury, and admission in bicycle and street sports compared to field sports were 1.77 (1.37-2.28), 4.99 (2.62-9.50), and 2.27 (1.42-3.61) respectively. CONCLUSION: This is the first nationwide epidemiologic study of pediatric sports-related TBI in Korea. The ratios of TBI, intracranial injury and admission were highest in bicycle and street sports. Prevention strategies for pediatric sports-related TBI can be developed according to sports types.

Prediction of Infarct Transmurality From C-Reactive Protein Level and Mean Platelet Volume in Patients With ST-Elevation Myocardial Infarction: Comparison of the Predictive Values of Cardiac Enzymes.

BACKGROUND: High C-reactive protein (CRP) and mean platelet volume (MPV) levels are associated with poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to evaluate the relationship between CRP level or MPV and infarct transmurality in patients with STEMI. METHODS: We retrospectively reviewed CRP level, MPV, and infarct transmurality in 112 STEMI patients who were assessed with contrast-enhanced cardiac magnetic resonance imaging. RESULTS: When the cut-off peak CRP level and MPV were set at 2.35 mg/dl and 7.3 fl using receiver operating characteristic curves analysis, the sensitivity was 67.3/69.2% and specificity was 76.7/76.7% for differentiating between the groups with and those without transmural involvement. Peak CRP level, MPV, peak creatine kinase-MB (CK-MB) level, and peak high-sensitivity cardiac troponin T (hs-cTnT) level had comparable predictive values for transmural involvement (area under the curve, 0.749, 0.761, 0.680, and 0.696, respectively). High peak CRP level and MPV were independent predictors of transmural involvement after adjusting for the peak CK-MB level, peak hs-cTnT level, baseline thrombolysis in myocardial infarction flow grade, and left ventricular ejection fraction (odds ratio: 5.16/5.42, 95% confidence interval: 1.84-14.50/2.03-14.47, P = 0.002/0.001, respectively) in the logistic regression analysis. CONCLUSION: The results of this study show that peak CRP level and MPV are predictive markers for transmural involvement. Their predictive power for transmural involvement is independent of and comparable to that of peak CK-MB and hs-cTnT levels.

Brachial-ankle pulse wave velocity and mean platelet volume as predictive values after percutaneous coronary intervention for long-term clinical outcomes in Korea: A comparable and additive study.

This study aimed to determine the association of the brachial-ankle pulse wave velocity (baPWV) and mean platelet volume (MPV) with the development of adverse outcomes after percutaneous coronary intervention (PCI). The baPWV and MPV were analyzed in 372 patients who underwent PCI, with the primary endpoint as cardiac death. The secondary endpoint was cardiovascular events (CVE): a composite of cardiac death, myocardial infarction (MI), target vessel revascularization (TVR), ischemic stroke, and stent thrombosis (ST). During the follow-up period (mean, 25.8 months), there were 21 cardiac deaths, 10 MIs including four events of ST, seven ischemic strokes, and 29 TVRs. The baPWV cut-off level was set at 1672 cm/s using the receiver operating characteristic curve; the sensitivity and specificity was 85.7 and 60.1%, respectively, to differentiate between the groups with and without cardiac death. The MPV cut-off level was set at 8.20 fL using the receiver operating characteristic curve; the sensitivity and specificity were 81 and 53.3%, respectively, to differentiate between the groups with and without cardiac death. Kaplan-Meier analysis revealed that the higher baPWV group (≥ 1672 cm/s) had a significantly higher cardiac death and CVE rate than the lower baPWV group (<1672 cm/s) (11.4 vs. 1.4%, log-rank: p < 0.0001; 25.3 vs. 7.5%, log-rank: p < 0.0001; respectively), and the higher MPV group (median, >8.20 fL,) had a significantly higher cardiac death and CVE rate than the lower MPV group (≤ 8.20 fL) (9.4 vs. 2.1%, log-rank: p = 0.0026; 23.8 vs. 6.8%, log-rank: p < 0.0001; respectively). Furthermore, the high baPWV and MPV groups were significantly associated with an increased risk of cardiac death. These results show that baPWV and MPV are predictive markers after PCI for cardiac death; they are also additively associated with a higher risk of cardiac death.

Usefulness of serum bilirubin levels as a biomarker for long-term clinical outcomes after percutaneous coronary intervention.

The aim of this study was to evaluate the prognostic value of serum total bilirubin on the development of adverse outcomes after percutaneous coronary intervention (PCI) besides high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B type natriuretic peptide (NT-proBNP). Serum total bilirubin, hs-cTnT, and NT-proBNP were analyzed in 372 patients who underwent PCI. The primary endpoint was cardiac death. There were 21 events of cardiac death during a mean of 25.8 months of follow-up. When the serum total bilirubin cut-off level (median value) was set to 0.58 mg/dL using the receiver operating characteristic curve, the sensitivity was 95.2 % and the specificity was 51.0 % for differentiating between the group with cardiac death and the group without cardiac death. Kaplan-Meier analysis revealed that the lower serum total bilirubin group (<0.58 mg/dL) had a significantly higher cardiac death rate than the higher serum total bilirubin group (≥0.58 mg/dL) (10.4 vs. 0.6 %, log-rank: P = 0.0001). In conclusion, low serum total bilirubin is a predictive marker for cardiac death after PCI.

Usefulness of mean platelet volume as a biomarker for long-term clinical outcomes after percutaneous coronary intervention in Korean cohort: a comparable and additive predictive value to high-sensitivity cardiac troponin T and N-terminal pro-B type natriuretic peptide.

The aim of this study was to determine the associations of the mean platelet volume (MPV) high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B type natriuretic peptide (NT-proBNP) with the development of adverse outcomes after percutaneous coronary intervention (PCI). MPV hs-cTnT and NT-proBNP were analyzed in 372 patients who underwent PCI. The primary endpoint was cardiac death. The secondary endpoint analyzed was cardiovascular events (CVE): the composite of cardiac death, myocardial infarction (MI), target vessel revascularization (TVR), ischemic stroke and stent thrombosis (ST). The median MPV hs-cTnT and NT-proBNP levels were 8.20 (IQR 7.70-8.70) fL, 0.291 (IQR 0.015-3.785) ng/mL, and 105.25 (IQR 50.84-1128.5) pg/mL, respectively. There were 21 events of cardiac death, 10 MI (including 4 events of ST), 7 ischemic strokes and 29 TVR during a mean of 25.8 months of follow-up. The Kaplan-Meier analysis revealed that the higher MPV group (>8.20 fL, median) had a significantly higher cardiac death rate than the lower MPV group (≤8.20 fL; 9.4% vs. 2.1%, log-rank: p = 0.0026). When the MPV cut-off level was set to 8.20 fL using the receiver operating characteristic curve, the sensitivity was 81% and the specificity was 53.3% for differentiating between the group with cardiac death and the group without cardiac death. This value was more useful in patients with myocardial injury (hs-cTnT ≥ 0.1 ng/mL) or heart failure (NT-proBNP ≥ 450 pg/mL). The results of this study show that MPV is a predictive marker for cardiac death after PCI; its predictive power for cardiac death is more useful in patients with myocardial injury or heart failure.

Clinical outcome prediction from mean platelet volume in patients undergoing percutaneous coronary intervention in Korean cohort: Implications of more simple and useful test than platelet function testing.

The aim of this study was to determine the associations of the mean platelet volume (MPV) with the development of adverse outcomes after percutaneous coronary intervention (PCI) and platelet reactivity. MPV and platelet function testing were analysed in 208 patients who underwent PCI. The primary endpoint was cardiac death. The secondary endpoint analysed was cardiovascular events (CVE): the composite of myocardial infarction (MI), target vessel revascularization (TVR), and stent thrombosis (ST). The median MPV level, aspirin reaction unit (ARU), P2Y12 reaction units (PRU) and P2Y12% inhibition (PI%) of clopidogrel were 8.55 (IQR 8.00-9.18) fl, 401.0 (IQR 389.3-442.0) ARU, 222.0 (IQR 169.0-272.3) PRU and 22 (IQR 9-38) %, respectively. We observed that high values of MPV were associated with elevated ARU (r = 0.165, p = 0.017) and decreased PI% (r = -0.167, p = 0.016). There were 10 events of cardiac death, 3 MI (including 1 event of ST), and 8 TVR during a mean of 7.6 months of follow-up. The Kaplan-Meier analysis revealed that the higher MPV group (≥8.55 fl, median) had a significantly higher cardiac death rate compared to the lower MPV group (<8.55 fl) (7.7% vs. 1.9%, log-rank: p = 0.035). However, aspirin or clopidogrel resistance (>550 ARU, <40 PI%, respectively) did not predict cardiac death. When the MPV cut-off level was set to 8.55 fl using the receiver operating characteristic curve, the sensitivity was 80% and the specificity was 51.5% for differentiating between the group with cardiac death and the group without cardiac death. This value was more useful in patients with clinical diagnosis of acute coronary syndrome (ACS). Furthermore, ACS patients with an MPV over 8.55 fl had high cardiac death and CVE risk without atorvastatin loading before PCI (Log-Rank = 0.0031, 0.0023, respectively). The results of this study show that MPV was a predictive marker for cardiac death after PCI; its predictive power for cardiac death was more useful in patients with ACS.

Effects of licochalcone A on the bioavailability and pharmacokinetics of nifedipine in rats: possible role of intestinal CYP3A4 and P-gp inhibition by licochalcone A.

The purpose of this study was to investigate the possible effects of licochalcone A (a herbal medicine) on the pharmacokinetics of nifedipine and its main metabolite, dehydronifedipine, in rats. The pharmacokinetic parameters of nifedipine and/or dehydronifedipine were determined after oral and intravenous administration of nifedipine to rats in the absence (control) and presence of licochalcone A (0.4, 2.0 and 10 mg/kg). The effect of licochalcone A on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activity was also evaluated. Nifedipine was mainly metabolized by CYP3A4. Licochalcone A inhibited CYP3A4 enzyme activity in a concentration-dependent manner with a 50% inhibition concentration (IC50 ) of 5.9 µm. In addition, licochalcone A significantly enhanced the cellular accumulation of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp. The area under the plasma concentration-time curve from time 0 to infinity (AUC) and the peak plasma concentration (Cmax ) of oral nifedipine were significantly greater and higher, respectively, with licochalcone A. The metabolite (dehydronifedipine)-parent AUC ratio (MR) in the presence of licochalcone A was significantly smaller compared with the control group. The above data could be due to an inhibition of intestinal CYP3A4 and P-gp by licochalcone A. The AUCs of intravenous nifedipine were comparable without and with licochalcone A, suggesting that inhibition of hepatic CYP3A4 and P-gp was almost negligible.