A Novel Tool for Distinguishing Type A Acute Aortic Syndrome from Heart Failure and Acute Coronary Syndrome.

Type A acute aortic syndrome (urgent AAS, UAAS) has a low incidence and high mortality rate; however, it is often missed or diagnosed late. Our aim was to create a new tool for distinguishing UAAS by using multiple modalities to select patients for CT aortography. This study included 75 patients with UAAS, 77 with acute coronary syndrome (ACS), and 81 with heart failure (HF) who received urgent treatment after propensity matching. Specific symptoms, past medical history, mediastinal width, region of interest (ROI) ratio in the lung base/apex, D-dimers, and troponin I were investigated to differentiate UAAS from ACS and HF. The most significant variables were selected to create a new scoring system. The UAAS score exhibited a performance AUC of 0.982. A simple UAAS score >1, excluding ROI ratios in lung base/apex, showed an AUC of 0.977, a sensitivity of 96%, and specificity of 92.41%. The results were validated using an external data set of 292 patients (simple UAAS score > 1: AUC of 0.966, sensitivity 93.33%, and specificity 95.36%). The simple UAAS score may be a valuable tool for suspecting UAAS and may reduce the likelihood of misdiagnosis or performing unnecessary CT aortography.

Effect of a Real-Time Audio Ventilation Feedback Device on the Survival Rate and Outcomes of Patients with Out-of-Hospital Cardiac Arrest: A Prospective Randomized Controlled Study.

The purpose of this study was to evaluate the effect of real-time audio ventilation feedback on the survival of patients with an out-of-hospital cardiac arrest (OHCA) during advanced cardiac life support (ACLS) performed by paramedics. This research was a prospective randomized controlled study performed in Busan, South Korea, from July 2022 to December 2022. This study included 121 patients, ages 19 and up, who were transferred to the study site, excluding 91 patients who did not receive CPR under a doctor's direction as well as those who had a '(DNR)' order among 212 adult CA patients. OHCA patients' clinical prognosis was compared by being randomly assigned to either a general manual defibrillator (NVF) group (N = 58) or a manual defibrillator with an audio ventilation feedback (AVF) group (N = 63). To verify the primary outcome, the cerebral performance category (CPC), return of spontaneous consciousness (ROSC), 30h survival, and survival discharge were compared. Multivariate logistic regression was conducted to analyze the association between the audio-feedback manual defibrillator (AVF) and the ROSC of OHCA patients. This study analyzed 121 patients among 212 OHCA patients. The ROSC (AVF group: 32 {26.4%} vs. NVF group: 21 {17.3%}), 24 h survival (AVF group: 24 {19.8%} vs. NVF group: 11 {9.0%}), and survival discharge (AVF group: 12 {9.9%} vs. NVF group: 6 {4.9%}) were higher in the AVF group than the NVF group. However, upon analyzing CPC scores in the surviving patients between the two groups, there was no significant difference (AVF group: 4.1 ± 1.23 vs. NVF group:4.7 ± 1.23, p = 1.232). Multivariate logistic regression analysis showed that the use of AVF was associated with a higher ROSC (odds ratio {OR}, 0.46; 95% confidence interval {CI}, 0.23-0.73; p < 0.01) and higher survival at 30 h (OR, 0.63; 95% CI, 0.41-0.98; p = 0.01).

"Elbow-Lock" Chest Compression Method in the Setting of Single Rescuer Pediatric Cardiopulmonary Resuscitation: A Crossover Simulation Study.

BACKGROUND: We designed a new 1-handed chest compression method, the "elbow-lock" chest compression (ELCC), for a single rescuer in pediatric cardiopulmonary resuscitation (CPR). Then, we compared the effectiveness between the ELCC and standard chest compression (SCC) method. METHODS: This prospective, randomized controlled, crossover simulation trial studied 34 emergency medical professionals, including physicians, nurses, and EMTs. We compare the quality of chest compression and fatigue point time between the ELCC and the SCC. RESULTS: Participants who performed the ELCC method maintained a proper depth of compression compared with SCC method (50.0 ± 0.3 mm vs 40.5 ± 0.4 mm, P < 0.001). However, the 2 methods did not differ in terms of compression velocity since neither reached the standard velocity (96.7 ± 7.1/minutes vs 91.7 ± 7.0/minutes, P < 0.016). With respect to the overall score, ELCC was more effective than the SCC (91.6 ± 3.7% vs 85.3 ± 8.8%, P = 0.002). In addition, the fatigue point time was slower in the ELCC group than the SCC group (7.3 ± 0.3/minutes vs 6.1 ± 0.4/minutes, P < 0.001). CONCLUSIONS: The single rescuer ELCC method is an effective alternative to the SCC method for pediatric CPR because the ELCC method can prevent elbow flexion.Trial registration: Our research is simulation manikin study. So we do not need to "trial registration".

Changes in the pattern of suicide attempters visiting the emergency room after COVID-19 pandemic: an observational cross sectional study.

BACKGROUND: This study aimed to find out the change in the rate and pattern of suicide attempts during severe acute respiratory syndrome COVID-19 pandemic period. METHODS: This study was a retrospective analysis of data collected as a part of an emergency room-based post-suicide management program. The data were collected through interviews and from medical records of suicide attempts, maintained in the emergency room, from January 19 to October 31, 2020, during the "COVID-19 period," and those who attempted suicide from January 19 to October 31, 2019 "pre-COVID-19 period." We extracted educational background, marital status, occupation, presence of domestic partner, history of mental illness, alcohol consumption, history of previous suicide attempts; suicide attempt method and location (i.e., at home or a place other than home) at the time of attempt, and whether the attempt was a mass suicide. In addition, we compared patient severity between "COVID-19 period" and "pre-COVID-19 period" using the initial KTAS (South Korean triage and acuity scale) level, consciousness level, and systolic blood pressure. In 2012, KTAS was developed through the Ministry of Health and Welfare's research project to establish triage system in South Korea. RESULTS: The analysis of the number of suicide attempts during "pre-COVID-19 period" and " COVID-19 period" showed that the number of suicide attempts during "COVID-19 period" (n = 440) increased compared to the "pre-COVID-19 period" (n = 400). Moreover, the method of suicide attempts during "COVID-19 period" included overdose of drugs such as hypnotics, antipsychotics, and pesticides that were already possessed by the patient increased compared to the "pre-COVID-19 period" (P < 0.05). At the time of the visit to the emergency room, high KTAS level, low level of consciousness, and low systolic blood pressure, were observed, which were significantly different between "COVID-19 period" and "pre-COVID-19 period" (P < 0.05). CONCLUSION: With the worldwide COVID-19 virus spread, suicide rate and suicide attempts at home have significantly increased. In addition, patient severity was higher in the "COVID-19 period" than that in the "pre-COVID-19 period." The increasing suicide attempt rate should be controlled by cooperation between the emergency room and regional organizations.

The Poisoning Information Database Covers a Large Proportion of Real Poisoning Cases in Korea.

The poisoning information database (PIDB) provides clinical toxicological information on commonly encountered toxic substances in Korea. The aim of this study was to estimate the coverage rate of the PIDB by comparing the database with the distribution of toxic substances that real poisoning patients presented to 20 emergency departments. Development of the PIDB started in 2007, and the number of toxic substances increased annually from 50 to 470 substances in 2014. We retrospectively reviewed the medical records of patients with toxic exposure who visited 20 emergency departments in Korea from January to December 2013. Identified toxic substances were classified as prescription drug, agricultural chemical, household product, animal or plant, herbal drug, or other. We calculated the coverage rate of the PIDB for both the number of poisoning cases and the kinds of toxic substances. A total of 10,887 cases of intoxication among 8,145 patients was collected. The 470 substances registered in the PIDB covered 89.3% of 8,891 identified cases related to poisoning, while the same substances only covered 45.3% of the 671 kinds of identified toxic substances. According to category, 211 prescription drugs, 58 agricultural chemicals, 28 household products, and 32 animals or plants were not covered by the PIDB. This study suggested that the PIDB covered a large proportion of real poisoning cases in Korea. However, the database should be continuously extended to provide information for even rare toxic substances.

Differences in Hands-off Time According to the Position of a Second Rescuer When Switching Compression in Pre-hospital Cardiopulmonary Resuscitation Provided by Two Bystanders: A Randomized, Controlled, Parallel Study.

The change of compressing personnel will inevitably accompany hands off time when cardiopulmonary resuscitation (CPR) is performed by two or more rescuers. The present study assessed whether changing compression by a second rescuer located on the opposite side (OS) of the first rescuer can reduce hands-off time compared to CPR on the same side (SS) when CPR is performed by two rescuers. The scenario of this randomized, controlled, parallel simulation study was compression-only CPR by two laypersons in a pre-hospital situation. Considering sex ratio, 64 participants were matched up in 32 teams equally divided into two gender groups, i.e. , homogenous or heterogeneous. Each team was finally allocated to one of two study groups according to the position of changing compression (SS or OS). Every team performed chest compression for 8 min and 10 sec, with chest compression changed every 2 min. The primary endpoint was cumulative hands-off time. Cumulative hands-off time of the SS group was about 2 sec longer than the OS group, and was significant (6.6 ± 2.6 sec vs. 4.5 ± 1.5 sec, P = 0.005). The range of hands off time of the SS group was wider than for the OS group. The mean hands-off times of each rescuer turn significantly shortened with increasing number of turns (P = 0.005). A subgroup analysis in which cumulative hands-off time was divided into three subgroups in 5-sec intervals revealed that about 70% of the SS group was included in subgroups with delayed hands-off time ≥ 5 sec, with only 25% of the OS group included in these subgroups (P = 0.033). Changing compression at the OS of each rescuer reduced hands-off time compared to the SS in prehospital hands-only CPR provided by two bystanders.

Performance of intubation with 4 different airway devices by unskilled rescuers: manikin study.

INTRODUCTION: This study was designed to compare the performances of 4 airway devices in achieving successful ventilation. METHODS: A randomized crossover trial was conducted to evaluate 4 airway devices: laryngeal mask airway (LMA), i-gel (iGEL), PENTAX Airway Scope (AWS), and Macintosh laryngoscope (MCL). Thirty-eight unskilled rescuers performed intubation on a manikin during chest compressions in normal and difficult airway scenarios. The time to ventilation, intubation success rate, and difficulty of intubation were measured. RESULTS: The time to ventilation of the airway devices in the normal scenario had a median value of 8.8 seconds (interquartile range, 7.3-10.5 seconds) for iGEL, 16.1 seconds (13.9-19.3 seconds) for LMA, 30.6 seconds (24.6-37.6 seconds) for AWS, and 35.0 seconds (29.5-45.9 seconds) for MCL. In the difficult airway scenario, the respective time to ventilation was 8.6 seconds (7.8-10.0 seconds), 15.3 seconds (14.3-20.2 seconds), 29.4 seconds (25.7-36.3 seconds) and 59.0 seconds (46.1-103.3 seconds). The success rates were 100% and 100% for LMA, 100% and 100% for iGEL, 97.4% and 94.7% for AWS, and 78.9% and 47.4% for MCL in the normal and difficult airway scenarios. The difficulties of intubation expressed as numerical rating scale were 2.0 and 2.0 (median values) for LMA, 1.0 and 2.0 for iGEL, 3.0 and 3.0 for AWS, and 4.0 and 5.0 for MCL in the normal and difficult airway scenarios, respectively. CONCLUSION: With novice intubators who were unfamiliar with the airway devices, the LMA, iGEL, and AWS were superior to the MCL for establishing an airway without interruption of chest compressions in a manikin study. Intubation with the iGEL was faster and easier than with the other airway devices.

Iopromide in combination with IFN-γ induces the activation of HMC-1 cells via IL-4 and MCP-1 expression.

In this study, we investigated whether IFN-γ has a role in contrast-medium-induced adverse reactions. Iopromide, a nonionic iodinated contrast agent, slightly induced mast cell proliferation and significantly increased the expression of IL-4 and MCP-1 at low doses. The pretreatment of cells with IFN-γ dramatically increased the expression of iopromide-induced IL-4 and MCP-1. An evaluation of mast cell activator secretion revealed that IFN-γ- or IL-4-pretreated HMC-1 cells released dramatically increased levels of ß-hexosaminidase and histamine when stimulated with iopromide. We also found that the migration of EoL-1 and THP-1 cells was significantly increased in culture conditions with iopromide-stimulated IL-4-pretreated HMC-1 cells. Taken together, our findings suggest that measuring IFN-γ or IL-4 levels in serum would be helpful as a potential biomarker of adverse patient reactions and that blocking IFN-γ or IL-4 may be crucial in preventing the delayed allergy-like reaction induced by contrast medium in patients with various diseases.

Effect of the potent CYP2D6 inhibitor sarpogrelate on the pharmacokinetics and pharmacodynamics of metoprolol in healthy male Korean volunteers.

1. Recently, we demonstrated that sarpogrelate is a potent and selective CYP2D6 inhibitor in vitro. Here, we evaluated the effect of sarpogrelate on the pharmacokinetics and pharmacodynamics of metoprolol in healthy subjects. 2. Nine healthy male subjects genotyped for CYP2D6*1/*1 or *1/*2 were included in an open-label, randomized, three treatment-period and crossover study. A single oral dose of metoprolol (100 mg) was administered with water (treatment A) and sarpogrelate (100 mg bid.; a total dose of 200 mg and treatment B), or after pretreatment of sarpogrelate for three days (100 mg tid.; treatment C). Plasma levels of metoprolol and α-hydroxymetoprolol were determined using a validated LC-MS/MS method. Changes in heart rate and blood pressure were monitored as pharmacodynamic responses to metoprolol. 3. Metoprolol was well tolerated in the three treatment groups. In treatment B and C groups, the AUCt of metoprolol increased by 53% (GMR, 1.53; 90% CI, 1.17-2.31) and by 51% (1.51; 1.17-2.31), respectively. Similar patterns were observed for the increase in Cmax of metoprolol by sarpogrelate. However, the pharmacodynamics of metoprolol did not differ significantly among the three treatment groups. 4. Greater systemic exposure to metoprolol after co-administration or pretreatment with sarpogrelate did not result in clinically relevant effects. Co-administration of both agents is well tolerated and can be employed without the need for dose adjustments.

Screening of non-steroidal anti-inflammatory drugs for inhibitory effects on the activities of six UDP-glucuronosyltransferases (UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) using LC-MS/MS.

Non-steroidal anti-inflammatory drugs (NSAIDs) are used widely to relieve pain and to decrease inflammation. Several clinical studies have reported that NSAIDs inhibit uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes. Therefore, the study evaluated the inhibitory potential of 15 NSAIDs on the activities of six UGT isoforms (i.e. UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) in human liver microsomes (HLMs). Among the 15 NSAIDs tested here, mefenamic acid and diclofenac inhibited all UGTs tested in this study. Piroxicam and niflumic acid inhibited UGT1A9 activity (IC50 = 73.8 µm and 0.38 µm, respectively) and naproxen selectively inhibited UGT2B7 activity (IC50 = 53.1 µm), whereas it did not inhibit the other UGTs tested (IC50 > 200 µm). Diflunisal inhibited the UGT1A1 (IC50 = 33.0 µm) and UGT1A9 (IC50 = 19.4 µm). Acetaminophen, fenoprofen, ibuprofen, ketoprofen, meloxicam, phenylbutazone, salicylic acid and sulindac showed negligible inhibitory effects on the six UGTs (IC50 > 100 µm). These results suggest that some NSAIDs have the potential to inhibit UGTs in vitro.

Glucuronidation of fimasartan, a new angiotensin receptor antagonist, is mainly mediated by UGT1A3.

1. Fimasartan is an angiotensin receptor II antagonist used to treat patients with hypertension. This drug is mainly excreted into bile as either the parent compound or a glucuronide conjugate. In this study, we examined the glucuronidation of fimasartan and characterized the UDP-glucuronosyltransferases (UGTs) responsible for the glucuronidation. 2. Only one type of fimasartan glucuronide was observed after incubation with pooled human liver microsomes (HLMs) and was identified as an N2-glucuronide based on comparison with an authentic standard. 3. Among the 12 UGT isoforms tested, UGT1A1, UGT1A3 and UGT2B7 showed catalytic activity toward fimasartan glucuronidation. The intrinsic clearance (CLint) of UGT1A3 was 68.5- and 21.4-fold higher than that of UGT1A1 and UGT2B7, respectively, and the estimated relative contribution of UGT1A3 in human liver was 94.1%. Both chemical inhibition and correlation studies demonstrated that fimasartan glucuronidation activity in HLMs was significantly related with UGT1A3 activity. Fimasartan glucuronide was identified as a substrate for P-glycoprotein (Pgp) and breast cancer response protein (BCRP). 4. These findings collectively indicate that UGT1A3 is the major UGT isoform responsible for the glucuronidation of fimasartan, and this glucuronide is excreted from hepatocytes via MDR1 and BCRP.

Enantioselective N-demethylation and hydroxylation of sibutramine in human liver microsomes and recombinant cytochrome p-450 isoforms.

The enantioselective metabolism of sibutramine was examined using human liver microsomes (HLM) and recombinant cytochrome P-450 (CYP) isoforms. This drug is metabolized to N-mono-desmethyl- (M1) and N,N-di-desmethylsibutramine (M2), and subsequent hydroxylation results in hydroxyl M1 (HM1) and hydroxyl M2 (HM2). No significant difference was noted in formation of M1from sibutramine between R- and S-sibutramine in HLM. However, S-enantiomers of M1 and M2 were preferentially metabolized to M2, HM1, and HM2compared to R-enantiomers in HLM, and intrinsic clearance (Clint) ratios of S-enantiomers/R-enantiomers were 1.97, 4.83, and 9.94 for M2, HM1, and HM2, respectively. CYP3A4 and CYP3A5 were only involved in the formation of M1, whereas CYP2B6 and CYP2C19 were responsible for all metabolic reactions of sibutramine. CYP2C19 and CYP3A5 displayed catalytic preference for S-sibutramine to S-M1, whereas CYP2B6 and CYP3A4 showed little or no stereoselectivity in metabolism of sibutramine to M1. In the case of M2 formation, CYP2B6 metabolized S-M1 more rapidly than R-M1 with a Clint ratio of 2.14. However, CYP2C19 catalyzed less S-M1 than R-M1 and the Clint ratio of S-M1 to R-M1 was 0.65. The most significant enantioselectivity was observed in formation of HM1 from M1, and HM2 from M2. CYP2B6 and CYP2C19 exhibited preferential catalysis of formation of hydroxyl metabolites from S-enantiomers rather than R-enantiomers. These results indicate that S-sibutramine was more rapidly metabolized by CYP isoforms than R-sibutramine, and that enantioselective metabolism needs to be considered in drug interactions involving sibutramine and co-administered drugs.

Does cardiac catheterization laboratory activation by electrocardiography machine auto-interpretation reduce door-to-balloon time?

OBJECTIVES: In an attempt to begin ST-segment elevation myocardial infarction (STEMI) treatment more quickly (referred to as door-to-balloon [DTB] time) by minimizing preventable delays in electrocardiogram (ECG) interpretation, cardiac catheterization laboratory (CCL) activation was changed from activation by the emergency physician (code heart I) to activation by a single page if the ECG is interpreted as STEMI by the ECG machine (ECG machine auto-interpretation) (code heart II). We sought to determine the impact of ECG machine auto-interpretation on CCL activation. METHODS: The study period was from June 2010 to May 2012 (from June to November 2011, code heart I; from December 2011 to May 2012, code heart II). All patients aged 18 years or older who were diagnosed with STEMI were evaluated for enrollment. Patients who experienced the code heart system were also included. Door-to-balloon time before and after code heart system were compared with a retrospective chart review. In addition, to determine the appropriateness of the activation, we compared coronary angiography performance rate and percentage of STEMI between code heart I and II. RESULTS: After the code heart system, the mean DTB time was significantly decreased (before, 96.51 ± 65.60 minutes; after, 65.40 ± 26.40 minutes; P = .043). The STEMI diagnosis and the coronary angiography performance rates were significantly lower in the code heart II group than in the code heart I group without difference in DTB time. CONCLUSION: Cardiac catheterization laboratory activation by ECG machine auto-interpretation does not reduce DTB time and often unnecessarily activates the code heart system compared with emergency physician-initiated activation. This system therefore decreases the appropriateness of CCL activation.

Selective inhibition of cytochrome P450 2D6 by Sarpogrelate and its active metabolite, M-1, in human liver microsomes.

The present study was performed to evaluate the in vitro inhibitory potential of sarpogrelate and its active metabolite, M-1, on the activities of nine human cytochrome (CYP) isoforms. Using a cocktail assay, the effects of sarpogrelate on nine CYP isoforms and M-1 were measured by specific marker reactions in human liver microsomes. Sarpogrelate potently and selectively inhibited CYP2D6-mediated dextromethorphan O-demethylation with an IC50 (Ki) value of 3.05 µM (1.24 µM), in a competitive manner. M-1 also markedly inhibited CYP2D6 activity; its inhibitory effect with an IC50 (Ki) value of 0.201 µM (0.120 µM) was more potent than that of sarpogrelate, and was similarly potent as quinidine (Ki, 0.129 µM), a well-known typical CYP2D6 inhibitor. In addition, sarpogrelate and M-1 strongly inhibited both CYP2D6-catalyzed bufuralol 1'-hydroxylation and metoprolol α-hydroxylation activities. However, sarpogrelate and M-1 showed no apparent inhibition of the other following eight CYPs: CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2E1, or CYP3A4/5. Upon 30-minute preincubation of human liver microsomes with sarpogrelate or M-1 in the presence of NADPH, no obvious shift in IC50 was observed in terms of inhibition of the nine CYP activities, suggesting that sarpogrelate and M-1 are not time-dependent inactivators. Sarpogrelate strongly inhibited the activity of CYP2D6 at clinically relevant concentrations in human liver microsomes. These observations suggest that sarpogrelate could have an effect on the metabolic clearance of drugs possessing CYP2D6-catalyzed metabolism as a major clearance pathway, thereby eliciting pharmacokinetic drug-drug interactions.

Heart rate-corrected QT interval predicts mortality in glyphosate-surfactant herbicide-poisoned patients.

BACKGROUND: Glyphosate-surfactant herbicide is promoted by the manufacturer as having no risks to human health. Glyphosate surfactant has recently been used with increasing frequency in suicide attempts, so clinical toxicologists occasionally encounter cases of severe systemic toxicity. The purpose of this study was to identify the early predictive factors of patients at risk for mortality and the usefulness of the corrected QT interval (QTc interval) for predicting mortality from glyphosate-surfactant intoxication. METHODS: This was a retrospective cohort study conducted from January 2005 to December 2012. A total of 153 patients with acute glyphosate-surfactant ingestion were included. To identify the predictive factors for mortality, objective variables easily assessed at presentation including previously reported predictive factors for mortality and severity were retrospectively analyzed for their association with mortality using univariate and multiple logistic analyses. RESULTS: The average age of the patients was 56 years (range, 19-93 years). Of the 153 patients, 19 (12.4%) died. The most common abnormal electrocardiogram findings were prolonged QTc interval followed by intraventricular conduction delay and first-degree atrioventricular block. Nonsurvivors had a significantly more prolonged QTc interval when compared with that of survivors (survivors: 453.4 ± 33.6 milliseconds vs nonsurvivors: 542 ± 32.0 milliseconds, P < .001). Corrected QT interval and age were associated with a significantly increased risk of death in a multiple logistic regression. In a receiver operating curve analysis, the QTc interval had significant discriminatory power. CONCLUSION: Prolonged QTc interval seems to be a useful prognostic factor for mortality in patients intoxicated with glyphosate-surfactant herbicide.

Performance assessment of the SOFA, APACHE II scoring system, and SAPS II in intensive care unit organophosphate poisoned patients.

This study assessed the ability of the Sequential Organ Failure Assessment (SOFA) and Acute Physiology, Chronic Health Evaluation (APACHE) II scoring systems, as well as the Simplified Acute Physiology Score (SAPS) II method to predict group mortality in intensive care unit (ICU) patients who were poisoned with organophosphate. The medical records of 149 organophosphate poisoned patients admitted to the ICU from September 2006 to December 2012 were retrospectively examined. The SOFA, APACHE II, and SAPS II were calculated based on initial laboratory data in the Emergency Department, and during the first 24 hr of ICU admission. The probability of death was calculated for each patient based on the SOFA score, APACHE II score, and SAPS II equations. The ability to predict group mortality by the SOFA score, APACHE II score, and SAPS II method was assessed using two by two decision matrices and receiver operating characteristic (ROC) curve analysis. A total of 131 patients (mean age, 61 yr) were enrolled. The sensitivities, specificities, and accuracies were 86.2%, 82.4%, and 83.2% for the SOFA score, respectively; 65.5%, 68.6%, and 67.9% for the APACHE II scoring system, respectively; and 86.2%, 77.5%, and 79.4% for the SAPS II, respectively. The areas under the curve in the ROC curve analysis for the SOFA score, APACHE II scoring system, and SAPS II were 0.896, 0.716, and 0.852, respectively. In conclusion, the SOFA, APACHE II, and SAPS II have different capability to discriminate and estimate early in-hospital mortality of organophosphate poisoned patients. The SOFA score is more useful in predicting mortality, and easier and simpler than the APACHE II and SAPS II.

In vitro metabolism of obovatol and its effect on cytochrome P450 enzyme activities in human liver microsomes.

Obovatol, a major constituent of the leaves of Magnolia obovata Thunb, is known to inhibit nuclear factor-κB activity and arachidonic acid-induced platelet aggregation. This study was performed to identify the metabolites of obovatol in human liver microsomes. Human liver microsomes incubated with obovatol in the presence of NADPH and/or UDPGA resulted in the formation of six metabolites, M1-M6. M1 and M2 were identified as hydroxyobovatol, on the basis of liquid chromatography/tandem mass spectrometric (LC-MS/MS) analysis. M1, M2 and obovatol were further metabolized to their glucuronide conjugates, obovatol-glucuronide (M3), obovatol-diglucuronide (M4) and hydroxyobovatol-glucuronide (M5 and M6). The inhibitory potency of obovatol on eight major human P450s was also investigated in human liver microsomes. In these experiments, obovatol strongly inhibited CYP2C19-mediated S-mephenytoin hydroxylase activity with an IC(50) value of 0.8 µM, which could have implications for drug-drug interactions.

Single nucleotide polymorphisms in SULT1A1 and SULT1A2 in a Korean population.

SULT1A1 and SULT1A2 are encoded on the same chromatid, and exhibit a 96% amino acid similarity. To screen for genetic variants in these two closely related genes, SULT1A1 and SULT1A2 were directly sequenced in 50 healthy Koreans. A total of 30 variations were identified in SULT1A1: eight in exons, thirteen in introns, and nine in the 5'-untranslated region. With regard to SULT1A2, 21 variants were identified, comprising seven in exons, five in introns, and nine in the 5'-untranslated region. Among these 51 variations, one in SULT1A1 and eight in SULT1A2 were previously unidentified, which include three coding variants (SULT1A2 R37Q, 110G>A; SULT1A2 G50S, 148G>A; SULT1A2 F286L, 3819C>A) and one null allele (SULT1A2 E217Stop, 3542G>T). Two LD blocks, major haplotype structures, and 7 haplotype-tagging SNPs were determined together for SULT1A1 and SULT1A2 as a single set. Frequencies of common functional variants were compared among ethnic groups. Since these two SULT enzymes are on the same chromatid in a parallel direction with overlapping substrate specificities, a combined analysis using LD and haplotype-tagging single-nucleotide polymorphisms (SNPs) will facilitate understanding of the variations in the sulfation reactions of a wide range of substrates, as compared with analysis of individual genes.

Clinical significance of national patients sample analysis: factors affecting mortality and length of stay of organophosphate and carbamate poisoned patients.

OBJECTIVES: This study considered whether there could be a change of mortality and length of stay as a result of inter-hospital transfer, clinical department, and size of hospital for patients with organophosphates and carbamates poisoning via National Patients Sample data of the year 2009, which was obtained from Health Insurance Review and Assessment Services (HIRA). The utility and representativeness of the HIRA data as the source of prognosis analysis in poisoned patients were also evaluated. METHODS: Organophosphate and carbamate poisoned patients' mortality and length of stay were analyzed in relation to the initial and final treating hospitals and departments, as well as the presence of inter-hospital transfers. RESULTS: Among a total of 146 cases, there were 17 mortality cases, and the mean age was 56.8 ± 19.2 years. The median length of stay was 6 days. There was no inter-hospital or inter-departmental difference in length of stay. However, it significantly increased when inter-hospital transfer occurred (transferred 11 days vs. non-transferred 6 days; p = 0.037). Overall mortality rate was 11.6%. The mortality rate significantly increased when inter-hospital transfer occurred (transferred 23.5% vs. non-transferred 7.0%; p = 0.047), but there was no statistical difference in mortality on inter-hospital and inter-department comparison at the initial treating facility. However, at the final treating facility, there was a significant difference between tertiary and general hospitals (5.1% for tertiary hospitals and 17.3% for general hospitals; p = 0.024), although there was no significant inter-departmental difference. CONCLUSIONS: We demonstrated that hospital, clinical department, length of stay, and mortality could be analyzed using insurance claim data of a specific disease group. Our results also indicated that length of stay and mortality according to inter-hospital transfer could be analyzed, which was previously unknown.

Effect of TSHAC on human cytochrome P450 activity, and transport mediated by P-glycoprotein.

TSAHC [4'-(p-toluenesulfonylamido)-4-hydroxychalcone] is a promising antitumorigenic chalcone compound, especially against TM4SF5 (four-transmembrane L6 family member 5)-mediated hepatocarcinoma. We evaluated the potential of TSAHC to inhibit the catalytic activities of nine cytochrome P450 isoforms and of P-glycoprotein (Pgp). The abilities of TSAHC to inhibit phenacetin Odeethylation (CYP1A2), coumarin 6-hydroxylation (CYP2A6), bupropion hydroxylation (CYP2B6), amodiaquine Ndeethylation (CYP2C8), diclofenac 4-hydroxylation (CYP2C9), omeprazole 5-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and midazolam 1'-hydroxylation (CYP3A) were tested using human liver microsomes. The P-gp inhibitory effect of TSAHC was assessed by [3H]digoxin accumulation in the LLCPK1-MDR1 cell system. TSAHC strongly inhibited CYP2C8, CYP2C9, and CYP2C19 isoform activities with Ki values of 0.81, 0.076, and 3.45 microM, respectively. It also enhanced digoxin accumulation in a dose-dependent manner in the LLCPK1-MDR1 cells. These findings indicate that TSAHC has the potential to inhibit CYP2C isoforms and P-gp activities in vitro. TSAHC might be used as a nonspecific inhibitor of CYP2C isoforms based on its negligible inhibitory effect on other P450 isoforms such as CYP1A2, CYP2A6, CYP2B6, CYP2D6, CYP2E1, and CYP3A.