A Comparison of Tracheal Intubation Using Direct Laryngoscope and Video Laryngoscope in the Sellick and Trendelenburg Position with That Using Direct Laryngoscope in the Supine Sniffing Position: A Randomized Controlled Trial

Background: Tracheal intubation in the Sellick and Trendelenburg position (ST position) can prevent pulmonary aspiration but increase the difficulty of tracheal intubation. We compared tracheal intubation using video and direct laryngoscopy in the ST position with direct laryngoscopy in the supine sniffing position to evaluate the overall intubation performance. Methods: One hundred and twenty patients were randomly assigned to three groups: direct laryngoscope in the supine sniffing position (control), direct laryngoscope in the ST position (ST direct), and video laryngoscope in the ST position (ST video). The primary outcome was the intubation time; secondary outcomes included the first attempt success rate of tracheal intubation, intubation difficulty scale score, operator’s subjective assessment of intubation difficulty, and modified Cormack–Lehane grades. Results: The median intubation times were greater in the ST direct (36.0 s) and video (34.5 s) than the control (28.0 s) groups. The first attempt success rate decreased in the ST direct (77.5%) but not the video (95.0%) group compared with the control group (100%). Conclusions: The challenges of tracheal intubation in the ST position, aimed at reducing the risk of pulmonary aspiration, can be mitigated by using a video laryngoscope, despite slightly longer intubation times

Exploring Data-Driven Components of Socially Intelligent AI through Cooperative Game Paradigms

The development of new approaches for creating more “life-like” artificial intelligence (AI) capable of natural social interaction is of interest to a number of scientific fields, from virtual reality to human–robot interaction to natural language speech systems. Yet how such “Social AI” agents might be manifested remains an open question. Previous research has shown that both behavioral factors related to the artificial agent itself as well as contextual factors beyond the agent (i.e., interaction context) play a critical role in how people perceive interactions with interactive technology. As such, there is a need for customizable agents and customizable environments that allow us to explore both sides in a simultaneous manner. To that end, we describe here the development of a cooperative game environment and Social AI using a data-driven approach, which allows us to simultaneously manipulate different components of the social interaction (both behavioral and contextual). We conducted multiple human–human and human–AI interaction experiments to better understand the components necessary for creation of a Social AI virtual avatar capable of autonomously speaking and interacting with humans in multiple languages during cooperative gameplay (in this case, a social survival video game) in context-relevant ways

Model-informed precision dosing in vancomycin treatment

Introduction: While vancomycin remains a widely prescribed antibiotic, it can cause ototoxicity and nephrotoxicity, both of which are concentration-associated. Overtreatment can occur when the treatment lasts for an unnecessarily long time. Using a model-informed precision dosing scheme, this study aims to develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model for vancomycin to determine the optimal dosage regimen and treatment duration in order to avoid drug-induced toxicity.Methods: The data were obtained from electronic medical records of 542 patients, including 40 children, and were analyzed using NONMEM software. For PK, vancomycin concentrations were described with a two-compartment model incorporating allometry scaling.Results and discussion: This revealed that systemic clearance decreased with creatinine and blood urea nitrogen levels, history of diabetes and renal diseases, and further decreased in women. On the other hand, the central volume of distribution increased with age. For PD, C-reactive protein (CRP) plasma concentrations were described by transit compartments and were found to decrease with the presence of pneumonia. Simulations demonstrated that, given the model informed optimal doses, peak and trough concentrations as well as the area under the concentration-time curve remained within the therapeutic range, even at doses smaller than routine doses, for most patients. Additionally, CRP levels decreased more rapidly with the higher dose starting from 10 days after treatment initiation. The developed R Shiny application efficiently visualized the time courses of vancomycin and CRP concentrations, indicating its applicability in designing optimal treatment schemes simply based on visual inspection

Impact of the Metabolic Syndrome on the Clinical Outcome of Patients with Acute ST-Elevation Myocardial Infarction

We sought to determine the prevalence of metabolic syndrome (MS) in patients with acute myocardial infarction and its effect on clinical outcomes. Employing data from the Korea Acute Myocardial Infarction Registry, a total of 1,990 patients suffered from acute ST-elevation myocardial infarction (STEMI) between November 2005 and December 2006 were categorized according to the National Cholesterol Education Program-Adult Treatment Panel III criteria of MS. Primary study outcomes included major adverse cardiac events (MACE) during one-year follow-up. Patients were grouped based on existence of MS: group I: MS (n=1,182, 777 men, 62.8±12.3 yr); group II: Non-MS (n=808, 675 men, 64.2±13.1 yr). Group I showed lower left ventricular ejection fraction (LVEF) (P=0.005). There were no differences between two groups in the coronary angiographic findings except for multivessel involvement (P=0.01). The incidence of in-hospital death was higher in group I than in group II (P=0.047), but the rates of composite MACE during one-year clinical follow-up showed no significant differences. Multivariate analysis showed that low LVEF, old age, MS, low high density lipoprotein cholesterol and multivessel involvement were associated with high in-hospital death rate. In conclusion, MS is an important predictor for in-hospital death in patients with STEMI

Bioanalysis of alpelisib using liquid chromatography–tandem mass spectrometry and application to pharmacokinetic study

Abstract Alpelisib is the first alpha-specific phosphatidylinositol-3-kinase (PI3K) inhibitor indicated for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative, PI3K catalytic subunit alpha-mutated, advanced, or metastatic breast cancer. Substantial attempts have been made to extend its clinical use to other types of cancer. Analytical methods proven to accurately quantify alpelisib would improve the reliability of the preclinical and clinical data of alpelisib. Therefore, we developed and validated a quantification method based on liquid chromatography–tandem mass spectrometry for alpelisib in mouse and human plasma samples. Alpelisib and an internal standard (IS; enzalutamide) were separated from endogenous substances using an XTerra MS C18 column with a linear gradient of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Multiple reaction monitoring transitions for alpelisib and the IS were m/z 442.1 > 328.0 and m/z 465.0 > 209.1, respectively. The calibration curve for alpelisib was confirmed to be linear in the range of 1–2000ng/mL in both mouse and human plasma. The intra- and inter-day accuracy and precision met the acceptance criteria, and no significant matrix effects were observed. Alpelisib was stable under various storage and handling conditions, and the carryover effect was overcome using the injection loop flushing method. We successfully used this assay to study the in vitro metabolic profiles and in vivo pharmacokinetics of alpelisib in mice. Here, to the best of our knowledge, we report for the first time a valid quantitative method for alpelisib in mouse and human plasma, which could aid in providing valuable pharmacokinetic information on alpelisib to increase its clinical availability

Динаміка та аналіз виробничого травматизму та професійних захворювань в Україні

Кожного року в Україні на виробництві травмується понад 10 тис. людей, з них гине понад 600 осіб. Оптимістична, на перший погляд, статистика, за якою травматизм на виробництві за роки незалежності України зменшився в десять разів, виявляється не такою вже й оптимістичною, коли аналізуються конкретні цифри

Successful Hemostasis with Recombinant Activated Factor VII in a Patient with Massive Hepatic Subcapsular Hematoma

Recombinant activated coagulation factor VII (rFVIIa) is known to be effective in the management of acquired deficiencies of factor VII and platelet function defects. But recently, rFVIIa has been successfully used to treat ongoing bleeding in disseminated intravascular coagulopathy (DIC) condition. The patient reported here was suspected to be suffering from toxic hepatitis on admission. After percutaneous liver biopsy, bleeding occurred and did not stop even after right hepatic artery embolization. The patient developed a severe hemorrhage that resulted in hypovolemic shock, hemoperitoneum, and a massive subcapsular hematoma. The patient then developed DIC due to massive transfusion, as well as acute liver necrosis. The patient was given 400 μg/kg of rFVIIa. Recombinant factor VIIa was administered in an attempt to control the bleeding. This stabilized the hemoglobin levels of the patient. The patient gradually recovered in 4 months. In conclusion, this case suggests that rFVIIa can be successfully used for the hemostasis of uncontrolled bleeding in DIC

Long-Term Clinical Outcomes according to Initial Management and Thrombolysis In Myocardial Infarction Risk Score in Patients with Acute Non-ST-Segment Elevation Myocardial Infarction

PURPOSE: There is still debate about the timing of revascularization in patients with acute non-ST-segment elevation myocardial infarction (NSTEMI). We analyzed the long-term clinical outcomes of the timing of revascularization in patients with acute NSTEMI obtained from the Korea Acute Myocardial Infarction Registry (KAMIR). MATERIALS AND METHODS: 2,845 patients with acute NSTEMI (65.6 +/- 12.5 years, 1,836 males) who were enrolled in KAMIR were included in the present study. The therapeutic strategy of NSTEMI was categorized into early invasive (within 48 hours, 65.8 +/- 12.6 years, 856 males) and late invasive treatment (65.3 +/- 12.1 years, 979 males). The initial- and long-term clinical outcomes were compared between two groups according to the level of Thrombolysis In Myocardial Infarction (TIMI) risk score. RESULTS: There were significant differences in-hospital mortality and the incidence of major adverse cardiac events during one-year clinical follow-up between two groups (2.1% vs. 4.8%, p or= 5 points). CONCLUSIONS: The old age, high Killip class, low ejection fraction, high TIMI risk score, and late invasive treatment strategy are the independent predictors for the long-term clinical outcomes in patients with NSTEMI.ope

Recessive C10orf2 mutations in a family with infantile-onset spinocerebellar ataxia, sensorimotor polyneuropathy, and myopathy

Recessive mutations in chromosome 10 open reading frame 2 (C10orf2) are relevant in infantile-onset spinocerebellar ataxia (IOSCA). In this study, we investigated the causative mutation in a Korean family with combined phenotypes of IOSCA, sensorimotor polyneuropathy, and myopathy. We investigated recessive mutations in a Korean family with two individuals affected by IOSCA. Causative mutations were investigated using whole exome sequencing. Electrophysiological analyses and muscle and nerve biopsies were performed, along with magnetic resonance imaging (MRI) of the brain and lower extremities. Compound heterozygous mutations c.1460C>T and c.1485-1G>A in C10orf2 were identified as causative of IOSCA. Skeletal muscle showed mitochondrial DNA (mtDNA) deletions. Both patients showed a period of normal development until 12–15 months, followed by ataxia, athetosis, hearing loss, and intellectual disability. Electrophysiological findings indicated motor and sensory polyneuropathies. Muscle biopsy revealed variations in the size and shape of myofibers with scattered, small, and angulated degenerating myofibers containing abnormal mitochondria; these observations are consistent with myopathy and may be the result of mtDNA deletions. Sural nerve biopsy revealed an axonal neuropathy. High-signal-intensity lesions in the middle cerebellar peduncles were correlated with clinical severity, and MRI of the lower legs was compatible with the hypothesis of length-dependent axonal degeneration. We identified novel compound heterozygous mutations of the C10orf2 gene as the cause of IOSCA with sensorimotor polyneuropathy and myopathy. Signs of motor neuropathy and myopathy were discovered for the first time in IOSCA patients with C10orf2 mutations. These results suggest that the clinical spectrum of IOSCA caused by C10orf2 mutations may be more variable than previously reported. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10048-014-0405-1) contains supplementary material, which is available to authorized users