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| 1 | Heparin resistance in severe thermal injury:a prospective cohort study显示文摘Background:Low molecular-weight heparin(LMWH)is routinely administered to burn patients for thromboprophylaxis.Some studies have reported heparin resistance,yet the mechanism(s)and prevalence have not been systematically studied.We hypothesized that nucleosomes,composed of histone structures with associated DNA released from injured tissue and activated immune cells in the form of neutrophil extracellular traps(NETs or NETosis),neutralize LMWH resulting in suboptimal anticoagulation,assessed by reduction in anti-factor Xa activity.Methods:Blood was sampled from>15%total body surface area(TBSA)burn patients receiving LMWH on days 5,10 and 14.Peak anti-factor Xa(AFXa)activity,anti-thrombin(ATIII)activity,cellfree DNA(cfDNA)levels and nucleosome levels were measured.Mixed effects regression was adjusted for multiple confounders,including injury severity and ATIII activity,and was used to test the association between nucleosomes and AFXa.Results:A total of 30 patients with severe burns were included.Mean TBSA 43%(SD 17).Twentythree(77%)patients were affected by heparin resistance(defined by AFXa activity<0.2 IU/mL).Mean peak AFXa activity across samples was 0.18 IU/mL(SD 0.11).Mean ATIII was 81.9%activity(SD 20.4).Samples taken at higher LWMH doses were found to have significantly increased AFXa activity,though the effect was not observed at all doses,at 8000 IU no samples were heparin resistant.Nucleosome levels were negatively correlated with AFXa(r=−0.29,p=0.050)consistent with the hypothesis.The final model,with peak AFXa as the response variable,was adjusted for nucleosome levels(p=0.0453),ATIII activity(p=0.0053),LMWH dose pre-sample(p=0.0049),drug given(enoxaparin or tinzaparin)(p=0.03),and other confounders including severity of injury,age,gender,time point of sample.Conclusions:Heparin resistance is a prevalent issue in severe burns.Nucleosome levels were increased post-burn,and showed an inverse association with AFXa consistent with the hypothesis that they may interfere with the anticoagulant effect of heparin in vivo and contribute to heparin resistance.Accurate monitoring of AFXa activity with appropriate therapy escalation plans are recommended with dose adjustment following severe burn injury. | Liam D Cato Benjamin Bailiff Joshua Price Christos Ermogeneous Jon Hazeldine William Lester Gillian Lowe Christopher Wearn Jonathan RB Bishop Janet M Lord Naiem Moiemen Paul Harrison | 2021 | Burns & Trauma2021，9，1： | 3 |
| 2 | 重组脊髓灰质炎病毒用于治疗复发胶质母细胞瘤(英文)显示文摘Background The prognosis of patients with recurrent World Health Organization(WHO)grade IV malignant glioma is dismal,and there is currently no effective therapy.We conducted a dose-finding and toxicity study in this population of patients,evaluating convection-enhanced,intratumoral delivery of the recombinant nonpathogenic polio-rhinovirus chimera(PVSRIPO).PVSRIPO recognizes the poliovirus receptor CD155,which is widely expressed in neoplastic cells of solid tumors and in major components of the tumor microenvironment.Methods We enrolled consecutive adult patients who had recurrent supratentorial WHO grade IV malignant glioma,confirmed on histopathological testing,with measurable disease(contrast-enhancing tumor of≥1 cm and≤5.5 cm in the greatest dimension).The study evaluated seven doses,ranging between 107 and 1010 50%tissue-culture infectious doses(TCID50),first in a dose-escalation phase and then in a dose-expansion phase.Results From May 2012 through May 2017,a total of 61 patients were enrolled and received a dose of PVSRIPO.Dose level-1(5.0×107TCID50)was identified as the phase 2 dose.One dose-limiting toxic effect was observed;a patient in whom dose level 5(1010TCID50)was administered had a grade 4 intracranial hemorrhage immediately after the catheter was removed.To mitigate locoregional inflammation of the infused tumor with prolonged glucocorticoid use,dose level 5 was deescalated to reach the phase 2 dose.In the dose-expansion phase,19%of the patients had a PVSRIPO-related adverse event of grade 3 or higher.Overall survival among the patients who received PVSRIPO reached a plateau of 21%(95%confidence interval,11 to 33)at 24 months that was sustained at 36 months.Conclusions Intratumoral infusion of PVSRIPO in patients with recurrent WHO grade IV malignant glioma confirmed the absence of neurovirulent potential.The survival rate among patients who receivedPVSRIPO immunotherapy was higher at 24 and 36 months than the rate among historical controls. | Desjardins A Gromeier M Herndon JE 2nd Beaubier N Bolognesi DP Friedman AH Friedman HS McSherry F Muscat AM Nair S Peters KB Randazzo D Sampson JH Vlahovic G Harrison WT McLendon RE Ashley D Bigner DD | 2018 | 中华神经外科疾病研究杂志2018，17，4： | 2 |
| 3 | Chemical associations of lead, cadmium, copper and zinc in street dusts and roadside soils显示文摘 | Harrison R M Laxen D P H Wilson S J | 1981 | Environmental Science and Technology1981，15，11： | 2 |
| 4 | Acute ischaemic stroke interventions: large vessel occlusion and beyond显示文摘Care for acute ischaemic stroke is one of the most rapidly evolving fields due to the robust outcomes achieved by mechanical thrombectomy.Large vessel occlusion(LVO)accounts for up to 38%of acute ischaemic stroke and comes with devastating outcomes for patients,families and society in the pre-intervention era.A paradigm shift and a breakthrough brought mechanical thrombectomy back into the spotlight for acute ischaemic stroke;this was because five randomised controlled trials from several countries concluded that mechanical thrombectomy for acute stroke offered overwhelming benefits.This review article will present a comprehensive overview of LVO management,techniques and devices used,and the future of stroke therapy.In addition,we review our institution experience of mechanical thrombectomy for posterior and distal circulation occlusion. | Ahmad Sweid Batoul Hammoud Sunidhi Ramesh Daniella Wong Tyler D Alexander Joshua Harrison Weinberg Maureen Deprince Jaime Dougherty Dimitri Jean-Mickael Maamari Stavropoula Tjoumakaris Hekmat Zarzour Michael R Gooch Nabeel Herial Victor Romo David M Hasan Robert H Rosenwasser Pascal Jabbour | 2020 | Stroke & Vascular Neurology2020，5，1： | 2 |
| 5 | Planar chips technology for miniaturization and integration of separation techniques into monitoring systems:capillary electrophoresis on a chip 显示文摘 | MANZ A HARRISON D J VERPOORTE E M J | 1992 | Chromatography1992，593，： | 2 |
| 6 | Aerosol insulin induces regulatory CD8 gamma delta T cells that prevent murine insulin dependent diabetes显示文摘 | DEMPSEY C M KRAMER D R | 1996 | J Exp Med1996，184，6： | 1 |
| 7 | Ethi cal Leadership: A Social Learning Perspective for Construct Development& Testing显示文摘 | BROWN M E TREVIN L K HARRISON D | 2005 | Organizational Behavior & Human Decision Processes2005，97，2： | 1 |
| 8 | Fabrication of photonic crystals for the visible spectrum by holo1graphic lithography显示文摘 | CAMPBELL M SHARP D N HARRISON M T | 2000 | Nature2000，404，6773： | 1 |
| 9 | A general theory of acute and chronic heart {ailure显示文摘 | Maciver D H Dayer M J Harrison A J | 2013 | Int J Cardiol2013，165，1： | 1 |
| 10 | The JAK/STAT Signaling Pathway显示文摘 | Rawlings J S Rosler K M Harrison D A | 2004 | J Cell Sci2004，17，： | 1 |
| 11 | The laC- NMR spectra of hemiterpenoid quinoline alkaloids and related prenylquinolines显示文摘 | BROW N GRUNDON M HARRISON D | 1980 | Tetrahedron1980，36，25： | 1 |
| 12 | Risk and predictors forpregnancy-related complications in women with heart disease 显示文摘 | Siu S C Sermer M Harrison D A | 1997 | Circulation1997，96，9： | 1 |
| 13 | Current and emerging therapies in nonalcoholic fatty liver disease显示文摘 | KASHI M R TORRES D M HARRISON S A | 2008 | Semin Liver Dis2008，28，： | 1 |
| 14 | Effect of spacing and age on nitrogen and phosphorus distribution in biomass of Eucalyptus camaldulensis,Eucalyptus pellita and Eucalyptus urophylla plantations in southeastern Brazil显示文摘 | Harrison R B Reis G G Reis M D G F | 2000 | Forest Ecology and Management2000，133，3： | 1 |
| 15 | A toolset supported approach for designing and testing virtual environment interaction techniques 显示文摘 | Willans J S Harrison M D | 2001 | International Journal for Human-Computer Studies2001，55，2： | 1 |
| 16 | Relationship between white cell count, neuropsychologic outcome, and microemboli in 161 patients undergoing coronary artery bypass surgery 显示文摘 | Whitaker D Stygall J Harrison M | 2006 | J Thorac Cardiovasc Surg2006，131，6： | 1 |
| 17 | Symbolic or substantive document? The influence of ethics codes on financial executives' decisions显示文摘 | Stevens J M Steensma H K Harrison D A Cochran P L | | 0，，2： | 1 |
| 18 | Neurofeedback and epilepsy显示文摘 | Monderer R S Harrison D M Hau S R | 2002 | Epilepsy & Behavior2002，，3： | 1 |
| 19 | Sibutramine may be associated with memory impairment显示文摘 | CLARK D W J HARRISON W M | 2004 | BMJ2004，329，： | 1 |
| 20 | Sarcomas and sarcomatoid and mixed malignant tumors of the kidney in adults显示文摘 | Farrow G M Harrison E G Utz D C | 1968 | Cancer1968，22，3： | 1 |
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