Assessment of Hypercoagulable State in Whole Blood in Sepsis Patients Using a Novel Microfluidic Dielectric Sensor

Background: There is an intimate link between inflammation and thrombosis, and patients with pro-inflammatory/infectious disorders develop a hypercoagulable state. Extant coagulation assays are unable to distinguish the pro-coagulant state of a patient's blood, require 2-3 mL of blood, and take 2-3 hours for processing. These assays are also typically examined in plasma and do not represent the contribution of blood cellular elements that participate in thrombosis in vivo. Thus, a point-of-care device for rapid, comprehensive assessment of whole blood coagulation is crucial to ensure appropriate and timely evaluation in critically ill patients. We have introduced a microfluidic sensor (ClotChip) that uses dielectric spectroscopy to provide such an assessment in a handheld platform. We have shown in clinical studies in patients with a hypocoagulable state that ClotChip is sensitive to both coagulation factor and platelet defects, allowing for a global assessment of blood coagulation status using <10 µL of whole blood and in <30 min. In this study, we optimized ClotChip to assess the blood coagulation status in patients with a hypercoagulable state. Methods: Citrated blood samples from 12 patients with a diagnosis of sepsis and 11 healthy donors as controls were obtained under an IRB-approved protocol and tested with ClotChip within 2 hours of collection. ClotChip readout curve was calculated as the temporal variation of blood dielectric permittivity at 1 MHz, and the time to reach a permittivity peak (T peak) was taken as an indicator of coagulation time based on our prior studies. To increase the sensitivity of the ClotChip T peak parameter to a hypercoagulable state, we used two different anticoagulants, recombinant thrombomodulin (rTM) and activated protein C (APC). To optimize the anticoagulant concentration, whole blood samples from healthy donors were treated in vitro with lipopolysaccharide to mimic a pro-coagulant state of blood and tested with ClotChip after adding various concentrations of rTM and APC. We concluded that a concentration of 5 µg/mL for rTM and 10 µg/mL for APC would result in an optimal change in T peak for detecting the pro-coagulant state. Since heparin (or lovenox) is routinely used in hospitalized patients, sepsis and control samples were pretreated with hepzyme at a final concentration of 2 IU/mL to reverse the heparin effect. The T peak parameter was measured and compared in (i) hepzyme only-, (ii) rTM-, and (iii) APC-treated samples. Data are reported as mean ± standard deviation. Two-tailed t test is used to test for statistical significance between groups, and P < 0.05 is considered statistically significant. In box-and-whiskers plots, the box represents the range from the first to the third quartile, the horizontal line represents the median, plus sign (+) represents mean of the data; whiskers extend to the maximum and minimum data values, and dots represent individual subject data. Results: In hepzyme only-treated samples, T peak was significantly prolonged at 478±137 sec in sepsis samples, as compared to 357±58 sec in controls (Figs. 1A, 1B). rTM treatment resulted in T peak of 503±128 sec for sepsis samples and 443±81 sec for controls, whereas APC treatment resulted in T peak of 1,095±850 sec for sepsis samples and 477±71 sec for controls (Figs. 1A, 1B). Although T peak was prolonged at baseline in hepzyme only-treated sepsis samples, no further prolongation was noted with rTM treatment (difference in T peak of 24±94 sec; Fig. 1C), as compared to rTM-treated controls (difference in T peak of 85±40 sec; Fig. 1C). However, with a difference in T peak of 616±804 sec, the APC-treated sepsis samples exhibited T peak prolongation when compared to hepzyme only-treated sepsis samples, whereas the APC-treated controls did not (difference in T peak of 119±64 sec; Fig. 1D). A comparison between the APC- and rTM-treated samples revealed a significant prolongation of T peak in sepsis samples (difference in T peak of 591±815 sec) when compared to controls (difference in T peak of 30±66 sec; Fig. 1E). Conclusions: Our studies identify a unique coagulation profile in sepsis patient blood using a microfluidic dielectric sensor. These data suggest that the addition of rTM or APC can enhance the sensitivity of the ClotChip T peak parameter for detecting the pro-coagulant state in whole blood. Ongoing studies are examining the coagulation profile in other pro-inflammatory and infectious states. Figure 1 Figure 1. Disclosures Suster: XaTek Inc.: Consultancy, Current holder of stock options in a privately-held company, Patents & Royalties, Research Funding. Mohseni: XaTek Inc.: Consultancy, Current holder of stock options in a privately-held company, Patents & Royalties, Research Funding. Nayak: BioChip Labs: Current Employment.

Studies on natural gas reserves multi-cycle growth law in Sichuan Basin based on multi-peak identification and peak parameter prediction

Research on predicting the growth trend of natural gas reserves will help provide theoretical guidance for natural gas exploration in Sichuan Basin. The growth trend of natural gas reserves in Sichuan Basin is multi-cycle and complex. The multi-cyclic peak is screened by the original multi-cyclic peak judgment standard. Metabolically modified GM(1,3) gray prediction method is used to predict the multi-cycle model parameters. The multi-cycle Hubbert model and Gauss model are used to predict the growth trend of natural gas reserves. The research results show that: (1) The number of cycles of natural gas reserves curve during 1956–2018 is 13. Natural gas reserves will maintain the trend of rapid growth in the short term. (2) Metabolism modified GM(1,3) gray prediction model can improve the accuracy of model prediction. The prediction accuracy of Hubbert model is higher than that of Gauss model. By 2030, the cumulative proven level of natural gas will reach 52.34%. The Sichuan Basin will reach its peak of proven lifetime reserves in the next few years.

FRI0361 CARTILAGE DEGRADATION IN PSORIATIC ARTHRITIS IS ASSOCIATED WITH INCREASED SYNOVIAL PERFUSION AS DETECTED BY MAGNETIC RESONANCE IMAGING

Background:Even though cartilage loss is a known feature of psoriatic arthritis (PsA), research is sparse on its role in the pathogenesis of PsA and its potential use for disease detection and monitoring. Using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and dynamic contrast-enhanced MRI (DCE MRI), research has shown that early cartilage loss is strongly associated with synovial inflammation in rheumatoid arthritis (RA). The aim of this study was to determine if acute inflammation is associated with early cartilage loss in small finger joints of patients with PsA.Objectives:Is local perfusion in PsA patients measured by dynamic MRI associated to local cartilage loss?Methods:Metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints of 17 patients with active PsA were evaluated by high-resolution 3 Tesla dGEMRIC and DCE MRI using a dedicated 16-channel hand coil. Semi-quantitative and quantitative perfusion parameters were calculated. Images were analyzed by two independent raters for dGEMRIC indices, PsA MRI scores (PsAMRIS), total cartilage thickness (TCT), and joint space width (JSW).Results:We found significant negative correlations between perfusion parameters (except Kep) and dGEMRIC indices, with the highest value at the MCP joints (KTrans: τ = -0.54, p = 0.01; Kep: τ= -0.02, p = 0.90; IAUC: τ = -0.51, p = 0.015; Initial Slope: τ = -0.54, p = 0.01; Peak: τ = -0.67, p = 0.002). Heterogeneous correlations were detected between perfusion parameters and both, total PsAMRIS and PsAMRIS synovitis sub-scores. No significant correlation was seen between any perfusion parameter and JSW and/or TCT.Conclusion:As examined by DCE MRI and dGEMRIC, there is a significant association between early cartilage loss and acute synovial inflammation in small finger joints of PsA patients.Figure 1.dGEMRIC maps (third digit) and perfusion maps (peak parameter) of MCP, PIP, and DIP joints in 26-year-old male (A and B) and a 59-year-old female (C and D) with PsA. Lower dGEMRIC values are illustrated in D, indicating more proteoglycan loss than in A. Higher peak values are depicted in C, indicating a higher severity of synovitis than in B. Peak parameter is illustrated in mM/l per second, dGEMRIC indices in ms.Disclosure of Interests:Philipp Sewerin Grant/research support from: AbbVie Deutschland GmbH & Co. KGBristol-Myers Squibb Celgene GmbHLilly Deutschland GmbHNovartis Pharma GmbH Pfizer Deutschland GmbHRheumazentrum Rhein-Ruhr, Consultant of: AMGEN GmbH AbbVie Deutschland GmbH & Co. KG Biogen GmbHBristol-Myers Squibb Celgene GmbH Chugai Pharma arketing Ltd. / Chugai Europe GmbHHexal Pharma Janssen-CilagGmbH Johnson & Johnson Deutschland GmbHLilly Deutschland GmbH / Lilly Europe / Lilly Global Novartis Pharma GmbH Pfizer Deutschland GmbH Roche Pharma Rheumazentrum Rhein-Ruhr Sanofi-Genzyme Deutschland GmbH Swedish Orphan Biovitrum GmbH UCB Pharma GmbH, Speakers bureau: AMGEN GmbH AbbVie Deutschland GmbH & Co. KG Biogen GmbHBristol-Myers Squibb Celgene GmbH Chugai Pharma arketing Ltd. / Chugai Europe GmbHHexal Pharma Janssen-CilagGmbH Johnson & Johnson Deutschland GmbHLilly Deutschland GmbH / Lilly Europe / Lilly Global Novartis Pharma GmbH Pfizer Deutschland GmbH Roche Pharma Rheumazentrum Rhein-Ruhr Sanofi-Genzyme Deutschland GmbH Swedish Orphan Biovitrum GmbH UCB Pharma GmbH, Daniel Abrar: None declared, Anja Müller-Lutz: None declared, Miriam Frenken: None declared, Karl Ludger Radke: None declared, Stefan Vordenbäumen: None declared, Matthias Schneider Grant/research support from: GSK, UCB, Abbvie, Consultant of: Abbvie, Alexion, Astra Zeneca, BMS, Boehringer Ingelheim, Gilead, Lilly, Sanofi, UCB, Speakers bureau: Abbvie, Astra Zeneca, BMS, Chugai, GSK, Lilly, Pfizer, Sanofi, Benedikt Ostendorf: None declared, Christoph Schleich: None declared

Quantitative Perfusion Analysis and Time Intensity Curve Analysis in Differential Diagnosis of Solid Pancreatic Tumors by Contrast-Enhanced Ultrasound. A Pilot Study

Contrast-enhanced ultrasound began to develop rapidly in recent years inRussia. Due to the physical properties of contrast agents it is possible to differentiate malignant and benign lesions. However, this method only involves a subjective evaluation of the obtained results. For the objectification of ultrasound with contrast enhancement implemented the function “TIC-analysis” (time intensity curve analysis). The aim: to assess the clinical value of the TIC-analysis in the differential diagnosis of adenocarcinoma of the pancreas and chronic pseudotumoral pancreatitis by contrast – enhanced ultrasound.Materials and methods. In A.V. Vishnevsky Institute of surgery contrast – enhanced ultrasound and TIC-analysis was performed on 23 patients with focal lesions of the pancreas. All patients were operated on, tumors were verified morphologically: adenocarcinoma of the pancreas in 18 (78%) patients, chronic pseudotumoral pancreatitis – in 5 (22%) patients.Results. The results about intensity of the tumors obtained by the TIC analysis do not allow to differentiate these pathological processes statistically significant (p > 0.05), which, in all probability, due to the fact that pancreatic adenocarcinoma and chronic pseudotumoral pancreatitis have similar morphological characteristics in the form of pronounced desmoplastic stromal response and fibrosis-hyalinosis, respectively. The “Time to peak| parameter allowed us to determine statistically significant that pancreatic adenocarcinoma had an early accumulation of contrast agent (average 16 sec) and early washout (from an average of 17 sec); the chronic pseudotumoral pancreatitis had the slow accumulation of contrast agent (average 85 sec) and slow washout (from an average of 86 seconds) (p < 0.05).Conclusion. The “Time to peak” parameter at ultrasound examination with echocontrast allows statistically significantly differentiate adenocarcinoma of the pancreas and chronic pseudotumoral pancreatitis.

Improved asymmetric peak parameter refinement

New expressions for the calculation of axial asymmetry peak shape parameter derivatives in the Finger, Cox and Jephcoat model [J. Appl. Cryst. (1994), 27, 892–900] are presented. Code utilizing the new expressions shows an improved range of convergence for powder diffraction peak shape refinements, particularly when the parameters are transformed to A = H + S and B = H − S.