Predictors of abnormal brain computed tomography findings in patients with acute altered mental status in the emergency department

Objective Brain computed tomography (CT) is commonly performed to diagnose acute altered mental status (AMS), a critically important symptom in many serious diseases. However, negative CT results are common, which result in unnecessary CT use. Therefore, this study aimed to determine the clinical factors associated with positive CT findings. Methods Patients with acute AMS selected from an emergency department-based registry were retrospectively evaluated. Patients with non-traumatic and noncommunicable diseases on initial presentation and with Glasgow Comal Scale scores of <15 were included in the study. Results Among the 367 brain CT results of patients with AMS during the study period, 146 (39.8%) were positive. In a multivariate analysis, the presence of focal neurologic deficit (odds ratio [OR], 132.6; 95% confidence interval [CI], 37.8 to 464.6), C-reactive protein level <2 mg/dL (OR, 3.9; 95% CI, 1.4 to 10.6), and Glasgow Comal Scale score <9 (OR, 2.4; 95% CI, 1.2 to 4.8) were significantly associated with positive brain CT results. Conclusion The presence of focal neurologic deficit, initial Glasgow Comal Scale score of <9, and initial C-reactive protein levels of <2 mg/dL can facilitate the selection of brain CT to diagnose patients with acute AMS in the emergency department

Comparison of CPR quality and rescuer fatigue between standard 30:2 CPR and chest compression-only CPR: a randomized crossover manikin trial

Objective We aimed to compare rescuer fatigue and cardiopulmonary resuscitation (CPR) quality between standard 30:2 CPR (ST-CPR) and chest compression only CPR (CO-CPR) performed for 8 minutes on a realistic manikin by following the 2010 CPR guidelines. Methods All 36 volunteers (laypersons; 18 men and 18 women) were randomized to ST-CPR or CO-CPR at first, and then each CPR technique was performed for 8 minutes with a 3-hour rest interval. We measured the mean blood pressure (MBP) of the volunteers before and after performing each CPR technique, and continuously monitored the heart rate (HR) of the volunteers during each CPR technique using the MRx monitor. CPR quality measures included the depth of chest compression (CC) and the number of adequate CCs per minute. Results The adequate CC rate significantly differed between the 2 groups after 2 minutes, with it being higher in the ST-CPR group than in the CO-CPR group. Additionally, the adequate CC rate significantly differed between the 2 groups during 8 minutes for male volunteers (p =0.012). The number of adequate CCs was higher in the ST-CPR group than in the CO-CPR group after 3 minutes (p =0.001). The change in MBP before and after performing CPR did not differ between the 2 groups. However, the change in HR during 8 minutes of CPR was higher in the CO-CPR group than in the ST-CPR group (p =0.007). Conclusions The rate and number of adequate CCs were significantly lower with the CO-CPR than with the ST-CPR after 2 and 6 minutes, respectively, and performer fatigue was higher with the CO-CPR than with the ST-CPR during 8 minutes of CPR.OAIID:RECH_ACHV_DSTSH_NO:220142014020983001RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A080158CITE_RATE:2.025FILENAME:comparison of cpr quality and rescuer fatigue between st-cpr and cc-only cpr_a randomized crossover manikin trial_scand j trauma resusc emerg med_2014.pdfDEPT_NM:의학과EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/d98e73fe-13a9-4bea-b265-cb96af10284f/linkCONFIRM:

Design, synthesis, and mechanism of action of 2-(3-hydroxy-5-methoxyphenyl)-6-pyrrolidinylquinolin-4-one as a potent anticancer lead

New 6- (or 6,7-) substituted 2-(hydroxyl substituted phenyl)quinolin-4-one derivatives were synthesized and screened for antiproliferative effects against cancer cell lines. Structure-activity relationship correlations were established and the most promising compound 2-(3-hydroxy-5-methoxyphenyl)-6-pyrrolidin-1-ylquinolin-4-one (6h) exhibited strong inhibitory activity against various human cancer cell lines, particularly non-small cell lung cancer NCI-H522. Additional studies suggested a mechanism of action resembling that of the antimitotic drug vincristine. The presence of a C-ring OH group in 6h will allow this compound to be converted readily to a water soluble and physiochemically stable hydrophilic prodrug. Compound 6h is proposed as a new anticancer lead compound

The novel synthesized 2-(3-(methylamino)phenyl)-6-(pyrrolidin-1-yl)quinolin-4-one (Smh-3) compound induces G2/M phase arrest and mitochondrial-dependent apoptotic cell death through inhibition of CDK1 and AKT activity in HL-60 human leukemia cells

2-Phenyl-4-quinolone series compounds have exhibited growth inhibitory influence on several human cancer cell lines. In this study, we investigated the effects of 2-(3-(methylamino)phenyl)-6-(pyrrolidin-1-yl)quinolin-4-one (Smh-3) on viability, cell cycle and apoptotic cell death which occurred in different leukemia cell lines (HL-60, U937 and K562) in a dose- and time-dependent manner, but which did not obviously impair the viability of normal human umbilical vein endothelial cells (HUVEC) in vitro. The approximate IC50 was 103.26 ± 4.59 nM for a 48 h treatment in HL-60 cells. Cell cycle analysis showed that 100 nM Smh-3 induced signi-ficant G2/M arrest in examined cells. Within 0, 12, 24 and 48 h of treatment, Smh-3 inhibited CDK1 activity and decreased protein levels of CDK1, cyclin A and cyclin B. Smh-3-induced chromatin condensation and DNA fragmentation were determined by DAPI and TUNEL staining. Cell apoptosis was significantly reduced after pretreatment with a pan-caspase inhibitor (Z-VAD-fmk) and results indicated that Smh-3-induced apoptosis was mainly mediated by activation of the caspase cascade in HL-60 cells. Results from colorimetric assays and Western blot analysis indicated that activities of caspase-9, -7 and -3 were promoted in Smh-3-treated HL-60 cells during cell apoptosis. Smh-3-induced apoptosis in HL-60 cells was accompanied by an apparent increase in ROS production, and protein levels of cytosolic cytochrome c, apoptotic protease activating factor-1 (Apaf-1) and apoptosis-inducing factor (AIF). Strikingly, Smh-3 induced apoptosis in HL-60 cells by simultaneously suppressing protein levels of AKT, p-AKT, p-mTOR and p-BAD and inducing BAD protein levels. Taken together, we conclude that Smh-3 acts against leukemia cells in vitro via G2/M phase arrest, down-regulation of AKT activity and induction of mitochondrial-dependent apoptotic pathways

Modified cardiovascular SOFA score in sepsis: development and internal and external validation

Background : The Sepsis-3 criteria introduced the system that uses the Sequential Organ-Failure Assessment (SOFA) score to define sepsis. The cardiovascular SOFA (CV SOFA) scoring system needs modification due to the change in guideline-recommended vasopressors. In this study, we aimed to develop and to validate the modified CV SOFA score. Methods : We developed, internally validated, and externally validated the modified CV SOFA score using the suspected infection cohort, sepsis cohort, and septic shock cohort. The primary outcome was 28-day mortality. The modified CV SOFA score system was constructed with consideration of the recently recommended use of the vasopressor norepinephrine with or without lactate level. The predictive validity of the modified SOFA score was evaluated by the discrimination for the primary outcome. Discrimination was assessed using the area under the receiver operating characteristics curve (AUC). Calibration was assessed using the calibration curve. We compared the prognostic performance of the original CV/total SOFA score and the modified CV/total SOFA score to detect mortality in patients with suspected infection, sepsis, or septic shock. Results : We identified 7,393 patients in the suspected cohort, 4038 patients in the sepsis cohort, and 3,107 patients in the septic shock cohort in seven Korean emergency departments (EDs). The 28-day mortality rates were 7.9%, 21.4%, and 20.5%, respectively, in the suspected infection, sepsis, and septic shock cohorts. The model performance is higher when vasopressor and lactate were used in combination than the vasopressor only used model. The modified CV/total SOFA score was well-developed and internally and externally validated in terms of discrimination and calibration. Predictive validity of the modified CV SOFA was significantly higher than that of the original CV SOFA in the development set (0.682 vs 0.624, p < 0.001), test set (0.716 vs 0.638), and all other cohorts (0.648 vs 0.557, 0.674 vs 0.589). Calibration was modest. In the suspected infection cohort, the modified model classified more patients to sepsis (66.0 vs 62.5%) and identified more patients at risk of septic mortality than the SOFA score (92.6 vs 89.5%). Conclusions : Among ED patients with suspected infection, sepsis, and septic shock, the newly-developed modified CV/total SOFA score had higher predictive validity and identified more patients at risk of septic mortality.National Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF2020R1A2C3004508) to Kyuseok Kim. National Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF2020R1F1A1052908) to Tae Gun Shin

Combination therapy of vitamin C and thiamine for septic shock in a multicentre, double-blind, randomized, controlled study (ATESS): study protocol for a randomized controlled trial

Background Septic shock is a life-threatening condition with underlying circulatory and cellular/metabolic abnormalities. Vitamin C and thiamine are potential candidates for adjunctive therapy; they are expected to improve outcomes based on recent experimental and clinical research. The aim of the Ascorbic Acid and Thiamine Effect in Septic Shock (ATESS) trial is to evaluate the effects of early combination therapy with intravenous vitamin C and thiamine on recovery from organ failure in patients with septic shock. Methods This study is a randomized, double-blind, placebo-controlled, multicentre trial in adult patients with septic shock recruited from six emergency departments in South Korea. Patients will be randomly allocated into the treatment or control group (1:1 ratio), and we will recruit 116 septic shock patients (58 per group). For the treatment group, vitamin C (50 mg/kg) and thiamine (200 mg) will be mixed in 50 ml of 0.9% saline and administered intravenously every 12 h for a total of 48 h. For the placebo group, an identical volume of 0.9% saline will be administered in the same manner. The primary outcome is the delta Sequential Organ Failure Assessment (SOFA) score (ΔSOFA = initial SOFA at enrolment – follow-up SOFA after 72 h). Discussion This trial will provide valuable evidence about the effectiveness of vitamin C and thiamine therapy for septic shock. If effective, this therapy might improve survival and become one of the main therapeutic adjuncts for patients with septic shock. Trial registration ClinicalTrials.gov, NCT03756220. Registered on 5 December 2018.This work was supported by a National Research Foundation of Korea grant funded by the Korean government (No. 2018R1C1B6006821). The government did not have any role in the study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges