Prediction of Critical Illness During Out-of-Hospital Emergency Care

CONTEXT: Early identification of nontrauma patients in need of critical care services in the emergency setting may improve triage decisions and facilitate regionalization of critical care. OBJECTIVES: To determine the out-of-hospital clinical predictors of critical illness and to characterize the performance of a simple score for out-of-hospital prediction of development of critical illness during hospitalization. DESIGN AND SETTING: Population-based cohort study of an emergency medical services (EMS) system in greater King County, Washington (excluding metropolitan Seattle), that transports to 16 receiving facilities. PATIENTS: Nontrauma, non-cardiac arrest adult patients transported to a hospital by King County EMS from 2002 through 2006. Eligible records with complete data (N = 144,913) were linked to hospital discharge data and randomly split into development (n = 87,266 [60%]) and validation (n = 57,647 [40%]) cohorts. MAIN OUTCOME MEASURE: Development of critical illness, defined as severe sepsis, delivery of mechanical ventilation, or death during hospitalization. RESULTS: Critical illness occurred during hospitalization in 5% of the development (n = 4835) and validation (n = 3121) cohorts. Multivariable predictors of critical illness included older age, lower systolic blood pressure, abnormal respiratory rate, lower Glasgow Coma Scale score, lower pulse oximetry, and nursing home residence during out-of-hospital care (P < .01 for all). When applying a summary critical illness prediction score to the validation cohort (range, 0-8), the area under the receiver operating characteristic curve was 0.77 (95% confidence interval [CI], 0.76-0.78), with satisfactory calibration slope (1.0). Using a score threshold of 4 or higher, sensitivity was 0.22 (95% CI, 0.20-0.23), specificity was 0.98 (95% CI, 0.98-0.98), positive likelihood ratio was 9.8 (95% CI, 8.9-10.6), and negative likelihood ratio was 0.80 (95% CI, 0.79- 0.82). A threshold of 1 or greater for critical illness improved sensitivity (0.98; 95% CI, 0.97-0.98) but reduced specificity (0.17; 95% CI, 0.17-0.17). CONCLUSIONS: In a population-based cohort, the score on a prediction rule using out-of-hospital factors was significantly associated with the development of critical illness during hospitalization. This score requires external validation in an independent populationPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85143/1/Seymour - JAMA-2010-747-54.pdf11

Is 3-Tesla Gd-EOB-DTPA-enhanced MRI with diffusion-weighted imaging superior to 64-slice contrast-enhanced CT for the diagnosis of hepatocellular carcinoma?

Objectives: To compare 64-slice contrast-enhanced computed tomography (CT) with 3-Tesla magnetic resonance imaging (MRI) using Gd-EOB-DTPA for the diagnosis of hepatocellular carcinoma (HCC) and evaluate the utility of diffusion-weighted imaging (DWI) in this setting. Methods: 3-phase-liver-CT was performed in fifty patients (42 male, 8 female) with suspected or proven HCC. The patients were subjected to a 3-Tesla-MRI-examination with Gd-EOB-DTPA and diffusion weighted imaging (DWI) at b-values of 0, 50 and 400 s/mm2. The apparent diffusion coefficient (ADC)-value was determined for each lesion detected in DWI. The histopathological report after resection or biopsy of a lesion served as the gold standard, and a surrogate of follow-up or complementary imaging techniques in combination with clinical and paraclinical parameters was used in unresected lesions. Diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values were evaluated for each technique. Results: MRI detected slightly more lesions that were considered suspicious for HCC per patient compared to CT (2.7 versus 2.3, respectively). ADC-measurements in HCC showed notably heterogeneous values with a median of 1.2±0.5×10−3 mm2/s (range from 0.07±0.1 to 3.0±0.1×10−3 mm2/s). MRI showed similar diagnostic accuracy, sensitivity, and positive and negative predictive values compared to CT (AUC 0.837, sensitivity 92%, PPV 80% and NPV 90% for MRI vs. AUC 0.798, sensitivity 85%, PPV 79% and NPV 82% for CT; not significant). Specificity was 75% for both techniques. Conclusions: Our study did not show a statistically significant difference in detection in detection of HCC between MRI and CT. Gd-EOB-DTPA-enhanced MRI tended to detect more lesions per patient compared to contrast-enhanced CT; therefore, we would recommend this modality as the first-choice imaging method for the detection of HCC and therapeutic decisions. However, contrast-enhanced CT was not inferior in our study, so that it can be a useful image modality for follow-up examinations

Oxidative Folding in Bacteria: Studies Using Single Molecule Force Spectroscopy

Oxidative folding, the process by which folding and disulfide oxidation occur in concert, is a critical step in the production of many extracellular proteins and is therefore centrally linked to a vast multitude of important physiological functions. The primary focus of this dissertation is the remarkable disulfide oxidoreductase DsbA, the sole catalyst of oxidative folding in Escherichia coli. DsbA was the first oxidative folding catalyst to be discovered, and remains the strongest known oxidant among the thioredoxin superfamily of disulfide oxidoreductases due to unique biochemical and biophysical properties. Through the activity of its substrate repertoire, which includes adhesion structures and toxins, DsbA is an essential component of many pathogenic processes and therefore is an active target for the development of novel antibiotics. Though DsbA has been analyzed through a host of biochemical, genetic, and cellular experiments over the quarter-century since its identification, the elucidation of certain mechanistic details of its catalytic process have proven elusive to conventional techniques. This primarily results from the experimental difficulties in independently monitoring the progress of folding and oxidation during oxidative folding that arise with conventional, ensemble-averaged approaches. In this work, single molecule force spectroscopy methods are applied to investigate the process of oxidative folding as catalyzed by DsbA. Through observing single substrate molecules as they undergo DsbA-catalyzed oxidative folding, a precise kinetic analysis of the enzyme is constructed. DsbA is demonstrated to be a highly effective catalyst of oxidative folding, outperforming its eukaryotic counterpart by substantial margins in every metric considered. This efficacy complements the strong preference for simpler disulfide connectivity patterns in the Escherichia coli proteome, which in conjunction likely represent a strategy for navigating the physiological demands that are imposed by the inherent speed of prokaryotic life, in which a generation can be as short as twenty minutes

Sensor, Signal, and Imaging Informatics in 2017.

Objective To summarize significant contributions to sensor, signal, and imaging informatics literature published in 2017.Methods PubMed® and Web of Science® were searched to identify the scientific publications published in 2017 that addressed sensors, signals, and imaging in medical informatics. Fifteen papers were selected by consensus as candidate best papers. Each candidate article was reviewed by section editors and at least two other external reviewers. The final selection of the four best papers was conducted by the editorial board of the International Medical Informatics Association (IMIA) Yearbook.Results The selected papers of 2017 demonstrate the important scientific advances in management and analysis of sensor, signal, and imaging information.ConclusionThe growth of signal and imaging data and the increasing power of machine learning techniques have engendered new opportunities for research in medical informatics. This synopsis highlights cutting-edge contributions to the science of Sensor, Signal, and Imaging Informatics

Hydrodynamic guiding for addressing subsets of immobilized cells and molecules in microfluidic systems

BACKGROUND: The interest in microfluidics and surface patterning is increasing as the use of these technologies in diverse biomedical applications is substantiated. Controlled molecular and cellular surface patterning is a costly and time-consuming process. Methods for keeping multiple separate experimental conditions on a patterned area are, therefore, needed to amplify the amount of biological information that can be retrieved from a patterned surface area. We describe, in three examples of biomedical applications, how this can be achieved in an open microfluidic system, by hydrodynamically guiding sample fluid over biological molecules and living cells immobilized on a surface. RESULTS: A microfluidic format of a standard assay for cell-membrane integrity showed a fast and dose-dependent toxicity of saponin on mammalian cells. A model of the interactions of human mononuclear leukocytes and endothelial cells was established. By contrast to static adhesion assays, cell-cell adhesion in this dynamic model depended on cytokine-mediated activation of both endothelial and blood cells. The microfluidic system allowed the use of unprocessed blood as sample material, and a specific and fast immunoassay for measuring the concentration of C-reactive protein in whole blood was demonstrated. CONCLUSION: The use of hydrodynamic guiding made multiple and dynamic experimental conditions on a small surface area possible. The ability to change the direction of flow and produce two-dimensional grids can increase the number of reactions per surface area even further. The described microfluidic system is widely applicable, and can take advantage of surfaces produced by current and future techniques for patterning in the micro- and nanometer scale

High-Resolution spectroscopy of the low-mass X-ray binary EXO 0748-67

We present initial results from observations of the low-mass X-ray binary EXO 0748-67 with the Reflection Grating Spectrometer on board the XMM-Newton Observatory. The spectra exhibit discrete structure due to absorption and emission from ionized neon, oxygen, and nitrogen. We use the quantitative constraints imposed by the spectral features to develop an empirical model of the circumsource material. This consists of a thickened accretion disk with emission and absorption in the plasma orbiting high above the binary plane. This model presents challenges to current theories of accretion in X-ray binary systems.Comment: 5 pages, 4 figures, accepted by A&A letters, XMM special issu