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Transfusion and coagulation management in liver transplantation

World Journal of Gastroenterology 2014年第20期20卷 6146-6158页

作者： Ben Clevenger susan v mallett Department of Anaesthesia Royal Free NHS Foundation Trust London NW3 2QG United Kingdom

There is wide variation in the management of coagulation and blood transfusion practice in liver transplantation. The use of blood products intraoperatively is declining and transfusion free transplantations take place ever more frequently. Allogenic blood products have been shown to increase morbidity and mortality. Primary haemostasis, coagulation and fibrinolysis are altered by liver disease. This, combined with intraoperative disturbances of coagulation, increases the risk of bleeding. Meanwhile, the rebalancing of coagulation homeostasis can put patients at risk of hypercoagulability and thrombosis. The application of the principles of patient blood management to transplantation can reduce the risk of transfusion. This includes: preoperative recognition and treatment of anaemia, reduction of perioperative blood loss and the use of restrictive haemoglobin based transfusion triggers. The use of point of care coagulation monitoring using whole blood viscoelastic testing provides a picture of the complete coagulation process by which to guide and direct coagulation management. Pharmacological methods to reduce blood loss include the use of anti-fibrinolytic drugs to reduce fibrinolysis, and rarely, the use of recombinant factor vIIa. Factor concentrates are increasingly used; fibrinogen concentrates to improve clot strength and stability, and prothrombin complex concentrates to improve thrombin generation. Non-pharmacological methods to reduce blood loss include surgical utilisation of the piggyback technique and maintenance of a low central venous pressure. The use of intraoperative cell salvage and normovolaemic haemodilution reduces allogenic blood transfusion. Further research into methods of decreasing blood loss and alternatives to blood transfusion remains necessary to continue to improve outcomes after transplantation.

关键词： Liver disease Transplantation Coagulation Transfusion Patient blood management Thromboelastography Cell salvage

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Thrombocytopenia in cirrhosis:Impact of fibrinogen on bleeding risk

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World Journal of Hepatology 2017年第6期9卷 318-325页

作者： Sonali v Thakrar susan v mallett Royal Free Perioperative Research Group Department of AnaesthesiaRoyal Free LondonLondon NW3 2QGUnited Kingdom

AIMTo investigate the relationship between baseline platelet count, clauss fibrinogen, maximum amplitude (MA) on thromboelastography, and blood loss in orthotopic liver transplantation (OLT). METHODSA retrospective analysis of our OLT Database (2006-2015) was performed. Baseline haematological indices and intraoperative blood transfusion requirements, as a combination of cell salvage return and estimation of 300 mls/unit of allogenic blood, was noted as a surrogate for intraoperative bleeding. Two groups: Excessive transfusion (> 1200 mL returned) and No excessive transfusion ( RESULTSOf 322 OLT patients, 77 were excluded due to fulminant disease; redo transplant or baseline haemoglobin (Hb) of P ≤ 0.001), platelet count (P = 0.005), clauss fibrinogen (P = 0.004) and heparinase MA (P = 0.001) were all statistically significantly different. Univariate logistic regression with a cut-off of platelets 9/L as the predictor and Haemorrhage as the outcome showed an odds ratio of 1.393 (95%CI: 0.758-2.563; P = 0.286). Review of receiver operating characteristic curves showed an area under the curve (AUC) for platelet count of 0.604 (95%CI: 0.534-0.675; P = 0.005) as compared with AUC for fibrinogen level, 0.678 (95%CI: 0.612-0.744; P ≤ 0.001). A multivariate logistic regression shows United Kingdom model for End Stage Liver Disease (P = 0.006), Hb (P = 0.022) and Fibrinogen (P = 0.026) to be statistically significant, whereas Platelet count was not statistically significant. CONCLUSIONPlatelet count alone does not predict excessive transfusion. Additional investigations, e.g., clauss fibrinogen and viscoelastic tests, provide more robust assessment of bleeding-risk in thrombocytopenia and cirrhosis.

关键词： Thrombocytopenia Cirrhosis Haemostasis Fibrinogen Liver transplantation

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Early acute kidney injury after liver transplantation: Predisposing factors and clinical implications

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World Journal of Hepatology 2017年第18期9卷 823-832页

作者： Suehana Rahman susan v mallett Brian R Davidson Royal Free Perioperative Research Group Department of Anaesthesia Royal Free Hospital Royal Free NHS Foundation Trust Department of Surgery Royal Free Hospital Royal Free NHS Foundation Trust

To investigate the additional clinical impact of hepatic ischaemia reperfusion injury (HIRI) on patients sustaining acute kidney injury (AKI) following liver transplantation. METHODSThis was a single-centre retrospective study of consecutive adult patients undergoing orthotopic liver transplantation (OLT) between January 2013 and June 2014. Early AKI was identified by measuring serum creatinine at 24 h post OLT (> 1.5 × baseline) or by the use of continuous veno-venous haemofiltration (CvvHF) during the early post-operative period. Patients with and without AKI were compared to identify risk factors associated with this complication. Peak serum aspartate aminotransferase (AST) within 24 h post-OLT was used as a surrogate marker for HIRI and severity was classified as minor (vere (> 5000 IU/L). The impact on time to extubation, intensive care length of stay, incidence of chronic renal failure and 90-d mortality were examined firstly for each of the two complications (AKI and HIRI) alone and then as a combined outcome. RESULTSOut of the 116 patients included in the study, 50% developed AKI, 24% required CvvHF and 70% sustained moderate or severe HIRI. Median peak AST levels were 1248 IU/L and 2059 IU/L in the No AKI and AKI groups respectively (P = 0.0003). Furthermore, peak serum AST was the only consistent predictor of AKI on multivariate analysis P = 0.02. AKI and HIRI were individually associated with a longer time to extubation, increased length of intensive care unit stay and reduced survival. However, the patients who sustained both AKI and moderate or severe HIRI had a longer median time to extubation (P ve care length of stay (P = 0.001) than those with either complication alone. Ninety-day survival in the group sustaining both AKI and moderate or severe HIRI was 89%, compared to 100% in the groups with either or neither complication (P = 0.049). CONCLUSIONHIRI has an important role in the devel

关键词： Hepatic ischaemia reperfusion injury Liver transplantation Perioperative care Acute kidney injury Marginal grafts

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Cirrhotic cardiomyopathy: Implications for the perioperative management of liver transplant patients

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World Journal of Hepatology 2015年第3期7卷 507-520页

作者： Suehana Rahman susan v mallett Department of Anaesthesia Royal Free London NHS Trust

Cirrhotic cardiomyopathy is a disease that has only recently been recognised as a definitive clinical entity. In the setting of liver cirrhosis, it is characterized by a blunted inotropic and chronotropic response t o s t r e s s, i m p a i r e d d i a s t o l i c r e l a x a t i o n o f t h e myocardium and prolongation of the QT interval in the absence of other known cardiac disease. A key pathological feature is the persistent over-activation of the sympathetic nervous system in cirrhosis, which leads to down-regulation and dysfunction of theβ-adrenergic receptor. Diagnosis can be made using a combination of echocardiography(resting and stress), tissue Doppler imaging, cardiac magnetic resonance imaging, 12-lead electrocardiogram and measurement of biomarkers. There are significant implications of cirrhotic cardiomyopathy in a number of clinical situations in which there is an increased physiological demand, which can lead to acute cardiac decompensation and heart failure. Prior to transplantation there is an increased risk of hepatorenal syndrome, cardiac failure following transjugular intrahepatic portosystemic shunt insertion and increased risk of arrhythmias during acute gastrointestinal bleeding. Liver transplantation presents the greatest physiological challenge with a further risk of acute cardiac decompensation. Peri-operative management should involve appropriate choice of graft and minimization of large fluctuations in preload and afterload. The avoidance of cardiac failure during this period has important prognostic implications, as there is evidence to suggest a long-term resolution of the abnormalities in cirrhotic cardiomyopathy.

关键词： Cirrhotic cardiomyopathy Liver transplantation Diastolic dysfunction Electrophysiological abnormalities Perioperative care

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Reducing transfusion requirements in liver transplantation

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World Journal of Transplantation 2015年第4期5卷 165-182页

作者： Ciara I Donohue susan v mallett Royal Free Perioperative Research Group (RoFPoR) Department of AnaesthesiaRoyal Free London NHS Trust

Liver transplantation(LT) was historically associated with massive blood loss and transfusion. Over the past two decades transfusion requirements have reduced dramatically and increasingly transfusionfree transplantation is a reality. Both bleeding and transfusion are associated with adverse outcomes in LT. Minimising bleeding and reducing unnecessary transfusions are therefore key goals in the perioperative period. As the understanding of the causes of bleeding has evolved so too have techniques to minimize or reduce the impact of blood loss. Surgical "piggyback" techniques, anaesthetic low central venous pressure and haemodilution strategies and the use of autologous cell salvage, point of care monitoring and targeted correction of coagulopathy, particularly through use of factor concentrates, have all contributed to declining reliance on allogenic blood products. Pre-emptive management of preoperative anaemia and adoption of more restrictive transfusion thresholds is increasingly common as patient blood management(PBM) gains momentum. Despite progress, increasing use of marginal grafts and transplantation of sicker recipients will continue to present new challenges in bleeding and transfusion management. variation in practice across different centres and within the literature demonstrates the current lack of clear transfusion guidance. In this article we summarise the causes and predictors of bleeding and present the evidence for a variety of PBM strategies in LT.

关键词： Liver transplantation Transfusion Blood conservation Patient blood management Coagulation

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XBP1 splicing contributes to endoplasmic reticulum stress-induced human islet amyloid polypeptide up-regulation

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Genes & Diseases 2024年第5期11卷 350-359页

作者： Yun Zhang susan Lin Jing Yao Wantong Cai Huaqiu Chen Ailikemu Aierken Zhe Wang Weihong Song National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijing 100053China Townsend Family Laboratories Department of PsychiatryThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Institute of Aging Key Laboratory of Alzheimer’s Disease of Zhejiang ProvinceSchool of Mental Health and the Affiliated Kangning HospitalWenzhou Medical UniversityWenzhouZhejiang 325000China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)WenzhouZhejiang 325001China

As a pathological hallmark of type 2 diabetes mellitus(T2DM),islet amyloid is formed by the aggregation of islet amyloid polypeptide(IAPP).Endoplasmic reticulum(ER)stress interacts with IAPP aggregates and has been implicated in the pathogenesis of *** examine the role of ER stress in T2DM,we cloned the hIAPP promoter and analyzed its promoter activity in human *** found that ER stress significantly enhanced hIAPP promoter activity and expression in human b-cells via triggering X-box binding protein 1(XBP1)*** identified a binding site of XBP1 in the hIAPP *** of this binding site by substitution or deletion mutagenesis significantly diminished the effects of ER stress on hIAPP promoter *** of XBP splicing by MKC3946 treatment inhibited ER stress-induced hIAPP up-regulation and improved human b-cell survival and *** study uncovers a link between ER stress and IAPP at the transcriptional level and may provide novel insights into the role of ER stress in IAPP cytotoxicity and the pathogenesis of T2DM.

关键词： b-cell function Endoplasmic reticulum stress Islet amyloid polypeptide Type 2 diabetes mellitus XBP1

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The Decarbonization of Construction—How Can Alkali-Activated Materials Contribute?

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Engineering 2024年第6期37卷 18-21页

作者： John L.Provis susan A.Bernal Zuhua Zhang Department of Materials Science and Engineering University of SheffieldSheffield S13JDUK Paul Scherrer Institut Villigen PSI 5232Switzerland School of Civil Engineering University of LeedsLeeds LS29JTUK School of Materials Sciences and Engineering Tongji UniversityShanghai 201804China

*** and context Enormous emphasis is currently being paid to the decarbonization of the global built environment as a leading priority for the engineering community and related industrial sectors[1].One of the main contributors to the overall emissions footprint of the built environment-and thus a cornerstone of efforts to achieve decarbonization-is the emissions profile of construction materials during their production and *** cement and concrete sector is the largest-volume contributor to the emissions incurred in meeting the world’s construction material needs and is therefore targeted in the discussion of the deep,rapid decarbonization that must be achieved in order to minimize irreversible damage to the Earth and its ecosystems.

关键词： Alkali corners irreversible

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A comprehensive review of genetic causes of obesity

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World Journal of Pediatrics 2024年第1期20卷 26-39页

作者： Marcio Jose Concepcion-Zavaleta Juan Eduardo Quiroz-Aldave Maria del Carmen Durand-vasquez Elman Rolando Gamarra-Osorio Juan del Carmen valencia de la Cruz Claudia Mercedes Barrueto-Callirgos susan Luciana Puelles-Leon Elena de Jesus Alvarado-Leon Frans Leiva-Cabrera Francisca Elena Zavaleta-Gutierrez Luis Alberto Concepcion-Urteaga Jose Paz-Ibarra Universidad Cientifica del Sur Bolivar 2150 AvenuePueblo Libre15084LimaPeru Division of Medicine Hospital de Apoyo ChepénChepenPeru Division of Family Medicine Hospital de Apoyo ChepénChepenPeru Division of Endocrinology Hospital Victor Lazarte EchegarayTrujilloPeru Division of Pediatrics Hospital de Apoyo ChepenChepenPeru Division of Internal Medicine Hospital de Apoyo ChepenChepenPeru Division of Genetics Universidad Nacional de TrujilloTrujilloPeru Division of Neonatology Hospital Belen de TrujilloTrujilloPeru Division of Internal Medicine Universidad Nacional de TrujilloTrujilloPeru Department of Medicine School of MedicineUniversidad Nacional Mayor de San MarcosLimaPeru

Background Obesity is a multifactorial chronic disease with a high,increasing worldwide *** causes account for 7%of the cases in children with extreme *** sources This narrative review was conducted by searching for papers published in the PubMed/MEDLINE,Embase and SciELO databases and included 161 *** search used the following search terms:"obesity","obesity and genetics","leptin","Prader-Willi syndrome",and"melanocortins".The types of studies included were systematic reviews,clinical trials,prospective cohort studies,cross-sectional and prospective studies,narrative reviews,and case *** The leptin-melanocortin pathway is primarily responsible for the regulation of appetite and body ***,several important aspects of the pathophysiology of obesity remain *** causes of obesity can be grouped into syndromic,monogenic,and polygenic causes and should be assessed in children with extreme obesity before the age of 5 years,hyperphagia,or a family history of extreme obesity.A microarray study,an analysis of the melanocortin type 4 receptor gene mutations and leptin levels should be performed for this *** are three therapeutic levels:lifestyle modifications,pharmacological treatment,and bariatric *** Genetic study technologies are in constant development;however,we are still far from having a personalized approach to genetic causes of obesity.A significant proportion of the affected individuals are associated with genetic causes;however,there are still barriers to its approach,as it continues to be underdiagnosed.

关键词： Leptin Melanocortin Obesity Prader-Willi syndrome Precision medicine

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Integrative genomic and transcriptomic profiling of pulmonary sarcomatoid carcinoma identifies molecular subtypes associated with distinct immune features and clinical outcomes

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Cancer Innovation 2024年第3期3卷 81-94页

作者： Sahil Seth Runzhe Chen Yang Liu Junya Fujimoto Lingzhi Hong Alexandre Reuben susan varghese Carmen Behrens Tina McDowell Luisa Solis Soto Cara Haymaker Annikka Weissferdt Neda Kalhor Jia Wu Xiuning Le Natalie I vokes Chao Cheng John v.Heymach Don L.Gibbons P.Andrew Futreal Ignacio IWistuba Humam Kadara Jianhua Zhang Cesar Moran Jianjun Zhang Department of Genomic Medicine The University of Texas MD Anderson Cancer CenterHoustonTexasUSA TRACTION The University of Texas MD Anderson Cancer CenterHoustonTexasUSA Graduate School of Biomedical Sciences The University of Texas MD Anderson and the University of Texas Health Science CenterHoustonTexasUSA Department of Thoracic/Head and Neck Medical Oncology The University of Texas MD Anderson Cancer CenterHoustonTexasUSA Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer CenterHoustonTexasUSA Department of Epidemiology The University of Texas MD Anderson Cancer CenterHoustonTexasUSA Department of Pathology The University of Texas MD Anderson Cancer CenterHoustonTexasUSA Department of Imaging Physics The University of Texas MD Anderson Cancer CenterHoustonTexasUSA Department of Medicine Baylor College of MedicineHoustonTexasUSA

Background:Pulmonary sarcomatoid carcinoma(PSC)is a rare and aggressive subtype of non-small cell lung cancer(NSCLC),characterized by the presence of epithelial and sarcoma-like *** molecular and immune landscape of PSC has not been well ***:Multiomics profiling of 21 pairs of PSCs with matched normal lung tissues was performed through targeted high-depth DNA panel,whole-exome,and RNA *** describe molecular and immune features that define subgroups of PSC with disparate genomic and immunogenic features as well as distinct clinical ***:In total,27 canonical cancer gene mutations were identified,with TP53 the most frequently mutated gene,followed by ***,most TP53 and KRAS mutations were earlier genomic events mapped to the trunks of the tumors,suggesting branching evolution in most PSC *** identified two distinct molecular subtypes of PSC,driven primarily by immune infiltration and *** Immune High(IM-H)subtype was associated with superior survival,highlighting the impact of immune infiltration on the biological and clinical features of localized ***:We provided detailed insight into the mutational landscape of PSC and identified two molecular subtypes associated with ***-H tumors were associated with favorable recurrence-free survival and overall survival,highlighting the importance of tumor immune infiltration in the biological and clinical features of PSCs.

关键词： genomic immune pulmonary sarcomatoid carcinoma survival

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Next Generation Transcriptome Sequencing and Quantitative Real-Time PCR Technologies for Characterisation of the Bemisia tabaci Asia 1 mtCOI Phylogenetic Clade

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Journal of Integrative Agriculture 2012年第2期11卷 281-292页

作者： susan Seal Mitulkumar v Patel Carl Collins John Colvin David Bailey Natural Resources Institute University of GreenwichChatham Maritime Kent ME4 4TBUnited Kingdom

A programme of functional genomics research is underway at the University of Greenwich,UK,to develop and apply genomics technologies to characterise an economically-important but under-researched Bemisia tabaci（Hemiptera：Aleyrodidae）,the Asia 1 mtCOI phylogenetic group.A comparison of this putative species from India with other important *** populations and insect species may provide targets for the development of more effective whitefly control *** a first step,next-generation sequencing（NGS）has been used to survey the transcriptome of adult female whitefly,with high quality RNA preparations being used to generate cDNA libraries for NGS using the Roche 454 Titanium DNA sequencing *** assemblies constructed from the resultant sequences（301 094 reads）using the software program CLC Genomics Workbench generated 3 821 core *** of a selection of these contigs with related sequences from other *** genetic groups has revealed good alignment for some genes（e.g.,HSP90）but misassemblies in other datasets（e.g.,the vitellogenin gene family）,highlighting the need for manual curation as well as collaborative international efforts to obtain accurate assemblies from the existing next generation sequence ***,data emerging from the NGS has facilitated the development of accurate and reliable methods for analysing gene expression based on quantitative real-time RT-PCR,illustrating the power of this approach to enable rapid expression analyses in an organism for which a complete genome sequence is currently lacking.

关键词： Bemisia tabaci whitefly transcriptome next generation sequencing quantitative real-time (QRT)-PCR Asia 1 mtCOI

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