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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 | Portal hypertension in polycystic liver disease patients does not affect wait-list or immediate post-liver transplantation outcomes显示文摘AIM To establish the impact of portal hypertension(PH) on wait-list/post-transplant outcomes in patients with polycystic liver disease(PCLD) listed for liver transplantation. METHODS A retrospective single-centre case controlled study of consecutive patients listed for liver transplantation over 12 years was performed from our centre. PH in the PCLD cohort was defined by the one or more of following parameters:(1) presence of radiological or endoscopic documented varices from our own centre or the referral centre;(2) splenomegaly(> 11 cm) on radiology inabsence of splenic cysts accounting for increased imaging size;(3) thrombocytopenia(platelets < 150 × 109/L); or(4) ascites without radiological evidence of hepatic venous outflow obstruction from a single cyst. RESULTS Forty-seven PCLD patients(F: M = 42: 5) were listed for liver transplantation(LT)(single organ, n = 35; combined liver-kidney transplantation, n = 12) with 19 patients(40.4%) having PH. When comparing the PH group with non-PH group, the mean listing age(PH group, 50.6(6.4); non-PH group, 47.1(7.4) years; P = 0.101), median listing MELD(PH group, 12; non-PH group, 11; P = 0.422) median listing UKELD score(PH group, 48; non-PH group, 46; P = 0.344) and need for renal replacement therapy(P = 0.317) were similar. In the patients who underwent LT alone, there was no difference in the duration of ICU stay(PH, 3 d; non-PH, 2 d; P = 0.188), hospital stay length(PH, 9 d; non-PH, 10 d; P = 0.973), or frequency of renal replacement therapy(PH, 2/8; non-PH, 1/14; P = 0.121) in the immediate post-transplantation period. CONCLUSION Clinically apparent portal hypertension in patients with PCLD listed for liver transplantation does not appear to have a major impact on wait-list or peri-transplant morbidity. | Neil Rajoriya Dhiraj Tripathi Joanna A Leithead Bridget K Gunson Sophie Lord James W Ferguson Gideon M Hirschfield | 2016 | World Journal of Gastroenterology2016，22，45： | 2 |
| 3 | The relationship of motor sells and adaptive behavior skills in young children with autism spectrum disorders显示文摘 | MacDonald M Lord C Ulrich D | | 0，，07： | 1 |
| 4 | The Madigan prostatectomy 显示文摘 | Dixon A R Lord P H Madigan M R | 1990 | J Urol1990，144，： | 1 |
| 5 | NLK is a novel therapeutic target for PTEN deficient tumour cells显示文摘 | Mendes-Pereira A M Lord C J Ashworth A | 2012 | PLoS One2012，7，47： | 1 |
| 6 | Evaluation of quantitative PCR reference genes for gene expression studies in Tribolium castaneum after fungal challenge显示文摘 | Lord J C Hartzer K Toutges M | | 0，，02： | 1 |
| 7 | Mangy mutt or furry friend?Anthropomorphism promotes animal welfare显示文摘 | Butterfield M E Hill S E Lord C G | 2012 | Journal of Experimental Social Psychology2012，48，4： | 1 |
| 8 | DNA repair and cisplatin resistance in non-small-cell lung cancer 显示文摘 | Rosell R Lord RV Taron M | 2002 | Lung cancer2002，38，3： | 1 |
| 9 | Leptin prevents the fall in plasma osteocalcin during starvation in male mice显示文摘 | Goldstone A P Howard J K Lord G M | 2002 | Biochem Biophys Res Commun2002，295，2： | 1 |
| 10 | DNA adducts and p53 mutations in a patient with aristolochic acid-associat- ed nephropathy 显示文摘 | Lord GM Hollstein M Arlt VM | 2004 | Am d Kidney Dis2004，43，4： | 1 |
| 11 | The gona- dotrophin-releasing hormone receptor maps to sheep chro- mosome 6 outside of the region of the FecB locus 显示文摘 | Montgomery G W Penty J M Lord E A | 1995 | Mammalian Genome: Official Journal of the International Mammalian Genome Society1995，6，6： | 1 |
| 12 | The role ofbacteria in lactational mastitis and some considerations of the use of antibiotic treatment 显示文摘 | Kvist L J Larsson B W Hall Lord M L | 2008 | Int Breastfeed J2008，3，1： | 1 |
| 13 | Acquiring new knowledge: The role of retaining human capital in acquisitions of high-tech firms 显示文摘 | Ranft A L Lord M D | 2000 | Journal of High Technology Management Research2000，11，： | 1 |
| 14 | Beneficial effects of Leptin on obesity,T cell hyporesponsiveness,and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency显示文摘 | Farooqi I S Matarese G Lord G M | 2002 | J Clin Invest2002，110，8： | 1 |
| 15 | Leptin modulates the T-cell immune response and reverses starvation induced immunosuppression 显示文摘 | Lord G M Matarese G Howard J K | 1998 | Nature1998，349，6696： | 1 |
| 16 | A new type V toxin-antitoxin system where mRNA for toxin GhoT is cleaved by antitoxin GhoS显示文摘 | WANG Xiaoxue LORD D M CHENG H Y | 2012 | Nature Chemical Biology2012，8，10： | 1 |
| 17 | DNA repair and cisplatin resistance in non-small-cell lung cancer显示文摘 | Rosell R Lord R V Taron M | 2002 | Lung Cancer2002，38，3： | 1 |
| 18 | DNA repair and cisplatin resistance in non-small cell lung cancer显示文摘 | Rosell R Lord R V Taron M | 2002 | Lung Cancer2002，38，3： | 1 |
| 19 | Design, synthesis, and evaluation in vitro of quinoline-8-carboxamides, a new class of poly ( adenosine-diphosphate-ribose ) polymerase-1 (PARP-1) inhibitor显示文摘 | LORD A MAHON M F THREADGRILL M D | 2009 | JMed Chem2009，52，3： | 1 |
| 20 | Leptin modulates the T- cell immunt response and reverse starvation induced immunosuppression 显示文摘 | LORD G M MATARESE G BOWARD J K | 1998 | Nature1998，，6696： | 1 |
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