37 research outputs found
How to minimize blood loss during liver surgery in patients with cirrhosis
No full textAbstractPatients with liver disease frequently have substantial changes in their haemostatic system. This is reflected in abnormal test results on routine coagulation screening assays such as the prothrombin time (PT), activated thromboplastin time (APTT) and platelet count. Traditionally, attempts were made to correct abnormalities in the haemostatic system as measured by routine coagulation assays prior to invasive procedures by infusion of platelets or fresh frozen plasma (FFP). Recent laboratory and clinical data have indicated that the haemostatic reserve in cirrhotic patients is relatively well maintained although the coagulation screening assays suggest otherwise. Pre-procedural correction of coagulation tests with blood products may therefore not be necessary, and may even have harmful side-effects. In particular, fluid overload resulting in exacerbation of portal hypertension by infusion of blood products may in fact promote bleeding. In recent years, it has become clear that reduction of the central and portal venous pressure by fluid restriction and avoidance of blood product transfusion is a beneficial strategy in minimizing bleeding during liver surgery in cirrhotic patients. Some investigators have even taken this a step further and suggested pre-procedural phlebotomy in liver transplant recipients. The aim of this review is to provide an overview of recent studies and developments which have changed our understanding of the clinical relevance of abnormal coagulation tests in patients with cirrhosis, and which have contributed to a reduction in blood loss and transfusion requirements when liver surgery is needed in these patients
Biliary complications after orthotopic liver transplantation
No full textPurpose of reviewThe incidence, pathogenesis and management of the most common biliary complications are summarized, with an emphasis on nonanastomotic biliary strictures (NAS) and potential strategies to prevent NAS after liver transplantation.Recent findingsNAS have variable presentations in time and localization, suggesting various underlying pathogeneses. Early-onset NAS (presentation within 1 year) have shown to be largely related to ischemia-induced bile duct injury, whereas late-onset NAS [>1 year after orthotopic liver transplantation (OLT)] have more immune-mediated causes. Cytotoxic hydrophobic bile salts and impaired biliary HCO3- secretion may also play a role in the occurrence of NAS. Recently, insufficient biliary epithelial regeneration capacity after transplantation has also been suggested to play a major role in the pathogenesis of NAS. A potential strategy to prevent NAS has been proposed to be preservation by machine perfusion instead of classical static cold storage. Although machine perfusion has been shown to be a better preservation method for the liver parenchyma, efficacy in preventing ischemic injury of the biliary epithelium is largely unknown.SummaryThe potential advantages of machine perfusion are very promising as it may provide better protection of the vulnerable bile ducts against ischemia-reperfusion injury. Clinical trials will be needed to demonstrate the impact of machine perfusion in reducing the incidence of biliary complications, especially NAS, after OLT
Open-book tests:Search behaviour, time used and test scores
No full text<p>Background: Because of the increasing medical knowledge and the focus of medical education on acquiring competencies, the use of open-book tests seems inevitable. Dealing with a large body of information, indicating which kind of information is needed to solve a problem, and finding and understanding that knowledge at the right moment are behaviours that cannot be assessed during closed-book tests.</p><p>Aims: To examine whether there is a relationship between students' search behaviour - using references or not when answering a question - during open-book tests and their test scores.</p><p>Method: Second- (N = 491) and third-year medical students (N = 325) participated in this study. Search behaviour was operationalized as the number of questions for which students consulted their references. Furthermore, we collected data on the time students spent on answering all open-book questions and their test scores. To determine the relations, we calculated Spearman's and Pearson's correlations.</p><p>Results: Second-and third-year students consulted their references for 87% and 73% of the questions and spent 5.0 and 4.3 min on answering an open-book question, respectively. We did not find significant correlations between search behaviour and test scores.</p><p>Conclusion: Both 'well' and 'poorer performing' students often consulted their references. Spending almost 5 min per open-book question in multiple choice format seems to be too much. More research is needed to establish optimal open-book test time and to explore how 'well performing' students use their references during open-book tests.</p>
Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.
No full textThe QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD
High-Dose Methylphenidate and Carboxylesterase 1 Genetic Variability in Patients With Attention-Deficit/Hyperactivity Disorder
No full textPURPOSE/BACKGROUND: Methylphenidate (MPH) is widely used to reduce symptoms of attention-deficit/hyperactivity disorder. Methylphenidate is metabolized by the carboxylesterase 1 (CES1) enzyme. Some patients need a very high dose of MPH to reach desired clinical effects, without having adverse effects. This may be due to differences in MPH pharmacokinetics (PK), potentially caused by DNA variants in CES1, the gene encoding the enzyme that metabolizes MPH. Here we describe 3 patients requiring high-dose MPH and investigated the CES1 gene.METHODS/PROCEDURES: The 3 patients were using short-acting MPH in a dose of 180 to 640 mg instead of the maximum advised dose of around 100 mg MPH in the Netherlands. Plasma concentrations of MPH were determined at scheduled time points (day-curve). Methylphenidate plasma concentrations were used for PK analysis using an earlier published 2-compartment PK population model of MPH. Individual data of the 3 patients were compared with simulated population data, when equivalent doses were used. In addition, CES1 was genotyped (number of gene copies and single nucleotide polymorphisms) using real-time polymerase chain reaction.FINDINGS/RESULTS: Pharmacokinetic analysis in all 3 patients showed lower plasma concentrations of MPH in comparison with the population data. The mean absorption time and volume of distribution of the central compartment were equal, but the elimination clearance was higher. However, CES1 genotyping revealed no variations that could explain a higher metabolism of MPH.IMPLICATIONS/CONCLUSIONS: In these 3 cases, we could not demonstrate a correlation between MPH clearance and known genetic variants of the CES1 gene.</p
Cross-national aspects of cyberbullying victimization among 14-17-year-old adolescents across seven European countries
No full textBackground: The increasing use of the Internet and social network sites (SNS) has created a new domain of socio-emotional development for adolescents. The aim of this cross-sectional study was to explore cybervictimization across seven European countries, in relation to socio-demographic, Internet use and psychosocial variables. Methods: A cross-sectional school-based study was conducted in the participating countries: Germany, Greece, Iceland the Netherlands, Poland, Romania and Spain. Anonymous self-completed questionnaires included sociodemographic data, internet usage characteristics, school achievement, parental control, the Internet Addiction Test and Achenbach's Youth Self-Report. Results: The highest rate of cyber victimization was found in Romania (37.3%) and the lowest in Spain (13.3%). Multiple logistic regression analyses gave differing results between countries. In Romania, Poland and Germany cyberbullying victimization was associated with SNS use, whereas Internet use was associated with increased odds of cybervictimization only in Romania. Cybervictimization was associated with greater internalizing behavior problems in all countries analysed, and with externalizing problems in all except Romania. Conclusions: Cyberbullying victimization is an on-going problem, which is subject to country-specific socio-demographic factors and diverse patterns of current Internet use and its development. Preventive measures should emphasize the integration of Internet communication technology education in educational contexts, and focus on the consistent association between cybervictimization and internalizing and externalizing difficulties. © 2018 The Author(s)
Injury of Peribiliary Glands and Vascular Plexus before Liver Transplantation Predicts Formation of Non-Anastomotic Biliary Strictures
No full textSimilar outcome after transplantation of moderate macrovesicular steatotic and nonsteatotic livers when the cold ischemia time is kept very short
No full textBackground: Livers with moderate (30-60%) macrovesicular steatosis have been associated with poor outcome after transplantation. Aim of this study was to examine the outcome after transplantation of livers with moderate macrovesicular steatosis when the cold ischemia time (CIT) is kept very short. Methods: Postoperative outcome of 19 recipients of a moderate steatotic liver were compared with a matched control group of 95 recipients of a nonsteatotic liver graft (1:5 ratio). We studied graft/patient survival rates, incidences of primary nonfunction, postoperative complications (classified according to the Clavien-Dindo classification), first-week postoperative hepatic injury serum markers (AST/ALT), and liver function tests (PT time/bilirubin/lactate). In addition, we studied reversal of graft steatosis in follow-up biopsies. Results: Median CIT in livers with moderate steatosis and in controls was below 8 h in both groups. Although short-and long-term patient/graft survival rates and results of liver function tests were similar, serum markers of hepatic injury and postoperative complications (especially grade IVa) were significantly higher in recipients of a moderate steatotic liver. Reversal of steatosis was seen in 9 of the 11 (82%) recipients with follow-up liver biopsies. Conclusion: Despite the association with severe postoperative complications, moderate macrovesicular steatotic livers can be used successfully for transplantation if the CIT is kept very short
Comparing peri-operative complications of paediatric and adult anaesthesia:A retrospective cohort study of 81 267 cases
No full textBACKGROUND: Comparisons of peri-operative complications associated with paediatric (≤16 years) and adult anaesthesia are poorly available, especially in which cardiac surgery, organ transplantation and neurosurgery are involved. OBJECTIVE: The aim of this study was to evaluate the nature and incidence of peri-operative complications that might be due to anaesthesia and to identify independent risk factors for complications in children and adults, including those undergoing cardiac surgery, organ transplantation and neurosurgery. DESIGN: Retrospective cohort study. SETTING: The study was performed at the University Medical Centre Groningen in the 4 years between 1 January 2010 and the 31 December 2013. MAIN OUTCOME MEASURES: Complications and their severity were graded according to the standard complication score (20 items) of the Dutch Society of Anaesthesia. Univariate and multivariate regression analysis was used to identify independent risk factors for the reported complications. RESULTS: A total of 81 267 anaesthetic cases were included. In the paediatric cohort, there were 410 (2.9%) complications and 1675 (2.5%) in the adults. In both cohorts age, American Society of Anaesthesiologists classification and emergency treatment were independent risk factors for complications. With respect to age, infants less than 1 year were at the highest risk, whereas in the adult cohort, increased age was related to a greater number of complications. The incidences of the specific complications were different between both cohorts. Upper airway obstruction was more frequently observed in paediatric patients (26%), whereas in the adults, complications with the highest incidence concerned conversion of regional-to-general anaesthesia (25%) and hypotension (17%). CONCLUSION: Risk factors for all peri-operative complications were similar for paediatric and adult anaesthesia. However, the incidence of specific complications differed between both age categories
Diffuse reflectance spectroscopy accurately quantifies various degrees of liver steatosis in murine models of fatty liver disease
No full textBackground: A real-time objective evaluation for the extent of liver steatosis during liver transplantation is currently not available. Diffuse reflectance spectroscopy (DRS) rapidly and accurately assesses the extent of steatosis in human livers with mild steatosis. However, it is yet unknown whether DRS accurately quantifies moderate/severe steatosis and is able to distinguish between micro-and macrovesicular steatosis. Methods: C57BL/6JolaHsd mice were fed wit a choline-deficient l-amino acid-defined diet (CD-AA) or a choline-sufficient l-amino acid-defined control diet (CS-AA) for 3, 8, and 20 weeks. In addition B6. V-Lepob/OlaHsd (ob/ob) mice and their lean controls were studied. A total of 104 DRS measurements were performed in liver tissue ex vivo. The degree of steatosis was quantified from the DRS data and compared with histopathological analysis. Results: When assessed by histology, livers of mice fed with a CD-AA and CS-AA diet displayed macrovesicular steatosis (range 0-74 %), ob/ob mice revealed only microvesicular steatosis (range 75-80 %), and their lean controls showed no steatosis. The quantification of steatosis by DRS correlated well with pathology (correlation of 0.76 in CD-AA/CS-AA fed mice and a correlation of 0.75 in ob/ob mice). DRS spectra did not distinguish between micro-and macrovesicular steatosis. In samples from CD-AA/CS-AA fed mice, the DRS was able to distinguish between mild and moderate/severe steatosis with a sensitivity and specificity of 86 and 81 %, respectively. Conclusion: DRS can quantify steatosis with good agreement to histopathological analysis. DRS may be useful for real-time objective evaluation of liver steatosis during liver transplantation, especially to differentiate between mild and moderate/severe steatosis
