C-reactive protein at ICU admission as a marker of early graft dysfunction after liver transplant. A prospective, single-center cohort study

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"apellidos" => "Herrera-Gutiérrez" "email" => array:1 [ 0 => "mehguci@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Intensive Care Medicine Unit, Regional University Hospital of Malaga, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Clinical Analysis Department, Regional University Hospital of Malaga, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Faculty of Medicine, Universidad de Málaga, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Proteína C reactiva al ingreso en UCI como marcador de disfunción temprana del injerto tras trasplante hepático. Estudio unicéntrico, prospectivo y de cohortes" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 837 "Ancho" => 2083 "Tamanyo" => 83171 ] ] "descripcion" => array:1 [ "en" => "ROC curve depicting relationship between CRP against in-hospital mortality. AuC: ROC area under curve; CRP: C reactive protein. CRP values depicted as 1/CRP." ] ] ] "textoCompleto" => "IntroductionOrthotopic liver transplantation (OLT) is the main treatment for patients with a severe liver disease, but this is a complex surgical procedure and subject to a high number of complications.<a class="elsevierStyleCrossRef" href="#bib0120">1</a> An important issue in the management of these patients is the evaluation of the function of the implanted organ but, considering the wide spectrum of functions performed by the liver, its assessment is not easy to undertake.Markers for cytolysis, biliary production, ammonia, lactate and coagulation factors synthesized by the liver are widely used for the assessment of graft function, but there is no clear agreement about how and when to use them.<a class="elsevierStyleCrossRefs" href="#bib0125">2,3</a> In this scenario, the identification of other useful parameters for the evaluation of graft function could potentially hasten the detection of severe early allograft dysfunction (EAD) and help to initiate measures to diminish its intensity or even halt its development.<a class="elsevierStyleCrossRef" href="#bib0135">4</a>Many tests have been proposed to increment the array of tools at our disposal such as the rate of elimination of molecules cleared by the liver (i.e. indocyanine green or C-methacetin),<a class="elsevierStyleCrossRefs" href="#bib0135">4–6</a> or a change in serum levels of different inflammatory markers.C-reactive protein (CRP) is an acute phase reactant<a class="elsevierStyleCrossRef" href="#bib0150">7</a> synthesized mainly by the liver, and its synthesis initiates about 6h after an inflammatory insult, with exponential increments every 8h, until its maximal peak 50h after the insult. Surgical procedures such as OLT are known to induce inflammation, therefore, an increase of CRP should be expected. Nonetheless, bearing in mind the role of the liver in its synthesis, disturbances in hepatic function should result in a dampened increase in CRP serum level.<a class="elsevierStyleCrossRef" href="#bib0155">8</a> Accordingly, CRP production will depend on one hand on the impact of the inflammatory stimulus of the surgery and on the other hand on the functional capability of the allograft.<a class="elsevierStyleCrossRef" href="#bib0155">8</a> For this reason, we hypothesize that when liver allograft function is altered, CRP production is blunted, and recognizing this will help the early detection of severe allograft dysfunction.<a class="elsevierStyleCrossRef" href="#bib0160">9</a>Patients and methodsStudy designWe conducted a prospective, single center, cohort study, registering a series of consecutive OLT recipient patients admitted to our intensive care unit (ICU) from February 2009 to February 2015. For the design of the study and the preparation of the manuscript, we adhered to the recommendations of the STROBE initiative (Strengthening the Reporting of Observational Studies in Epidemiology).<a class="elsevierStyleCrossRef" href="#bib0165">10</a>SettingThe ICU of the Regional University Hospital in Malaga, Spain. During the period covered by this study (2009–2015) all patients were managed according to an institutional hospital protocol covering all phases of the transplant process (preoperative, operative and postoperative stages) that was maintained without substantial changes.Our protocol includes the use of the piggy-back technique and end to end anastomosis of the common bile duct in most cases, immediate postoperative care in our ICU for all patients, and clear indications for the immunosuppressive strategy: calcineurin inhibitors plus steroids (the most frequently used), mammalian target of rapamycin inhibitors plus steroids or interleukin 2 receptor antibodies plus steroids according to patient's characteristics and past medical history.Ethics approval and consent to participateThis study was compliant with the principles of the Declaration of Helsinki and Good Clinical Practice Guidelines and approved by the Committee for Ethics in Research of the Regional University Hospital of Malaga.Informed consent was obtained on admission to the ICU by either the patient or next of kin. Confidentiality was assured by registering variables in a disaggregated database.Patient information and data collectionRecruitment was conducted between February 2009 and February 2015. A flow-chart of study recruitment is presented in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>. Patients admitted to the ICU for postoperative care after OLT that complied with the study protocol (samples of CRP could be taken at ICU admission and at 24 and 48h and did not present exclusion criteria) were enrolled in the study.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Exclusion criteria: age less than 18 years, emergent OLT after acute liver failure, clinical and microbiological evidence of active infection, and refusal from the patient or his/her representative to participate in the study.As per institutional hospital protocol, serum lactate, transaminases, INR, bilirubin, and creatinine are measured on admission to the ICU after the liver transplant and every 12h until discharge from the unit. Plasma CRP was additionally measured at ICU admission, 24 and 48h. A quantitative method based on polystyrene coated monoclonal antibodies against CRP was used (Dimension Vista 1500 System®). This test detects CRP concentrations in a range of 2.9–190mg/L.Prior definitionsSevere dysfunction of liver allograft was defined using the MEAF (Model for Early Allograft Function Scoring) score<a class="elsevierStyleCrossRef" href="#bib0170">11</a> with a cut-off over 8 points. This score is calculated by an equation comprising of three markers usually measured to evaluate liver function: ALT, INR, and total bilirubin.The MEAF score was developed when recruitment was closing but due to the fact that all the required variables were already registered prospectively in our database, the statistical analysis was not due to be performed until the end of the recruiting period and in our population we found that this score performs better,<a class="elsevierStyleCrossRef" href="#bib0125">2</a> we opted for its inclusion in the study. The primary outcome was severe graft dysfunction by MEAF score and the secondary outcome was in-hospital mortality.Statistical analysisAs a first step, normality was probed with the Kolmogorov–Smirnov test, detecting that variables following a normal distribution were: MELD (Model for End-Stage Liver Disease), MEAF and CRP in days 1 and 3. Despite this fact and for the sake of readability of results, the mean and confidence interval of the mean were selected for the description of those continuous variables in which this parameter was more informative than the median. For the rest of variables, the median and interquartile range are the statistics shown. Categorical variables are presented as percentages. Chi-square, U-Mann Whitney, and Kruskal–Wallis tests were applied with a p-value <0.05. Corresponding Odds Ratio (OR) and 95% confidence interval of OR are shown when applicable.Being a prospective cohort and not having information about the standard deviation of CRP in these populations we were not able to calculate beforehand the sample size needed so we calculated the power of our results.To determine optimal cut-off level of CRP for detection of severe allograft dysfunction, a receiver operating characteristics (ROC) curve was drawn, its correspondent area under the curve (AuC) (95% confidence interval) calculated, and the Youden Index used to define the best cut-off point. In order to show an upward ROC curve, to simplify visual understanding of the results, 1/CRP was employed to draw the curve, after performing all calculations with raw CRP values.In order to test a relationship between CRP and outcome, a model of logistic regression was computed by the backward conditional stepwise method, including all variables with a statistical relationship below 0.15 (sex, age, chronic kidney disease, previous OLT, MELD previous to OLT, APACHE II, higher lactate, creatinine at admission, higher creatinine and CRP at admission) in the univariate analysis and severe EAD or in-hospital mortality as the dependent variable; these results are presented as OR (95% confidence interval).For statistical analysis and creation of figures the statistical package R 3.1.2 for OsX,<a class="elsevierStyleCrossRef" href="#bib0175">12</a> and Prism 6 for Mac Os X (GraphPad Software Inc®) were employed. In order to compute the power of our study we used the Statmate 2® for Windows software.ResultsOf 272 patients admitted after OLT, none showed clinical or microbiological signs of infection and 19 had acute liver disease. 253 patients did not show exclusion criteria, among them, a valid determination of CRP was performed at ICU admission in 183 patients (180 at 24 and 155 at 48h respectively).Mean age was 54.3 (52.8–55.7) years and 45 (24.6%) of our patients were female. Model for End-Stage Liver Disease (MELD) score before OLT was 16.5 (15.5–17.6) points and mean APACHE II at ICU admission was 14.4 (13.8–15.1). Arterial hypertension in 47 (25.7%), diabetes in 47 (25.7%) and chronic renal disease in 15 (8.2%) were registered as relevant comorbidities.Main indications for OLT were: alcoholic liver disease in 87 (47.5%), chronic viral hepatitis in 51 (27.9%), biliary tree diseases in 16 (8.7%), cryptogenic 12 (6.6%), and other 9.3%. Thirteen patients (7.1%) had a previous OLT.Median hospital stay before surgery was 1 (interquartile range 0–1) day, median ICU length of stay 3 (3–5) days, and total hospital length of stay 12 (9–20) days. In-hospital mortality was 10 cases (5.5%), 8 out of 183 (4.4%) in the early postoperative course during ICU stay and 2 out of 175 (1.1%) in the hospital ward after ICU discharge.Mean CRP at ICU admission 57.5 (51.6–63.3)mg/L, at 24h 80.1 (72.9–87.3)mg/L and at 48h 69.9 (62.5–77.4)mg/L. Mean lower value for CRP 52.3 (46.8–57.9)mg/L. Concentration of CRP and classic markers of liver function are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Twenty-six (14.2%) patients were diagnosed with severe EAD (MEAF score >8) and had higher mortality (23.1% vs 2.5%; OR 11.48 [95% CI 2.98–44.19]). CRP at ICU admission was 39.3 (29.8–48.7)mg/L, against 60.5 (53.9–67.0)mg/L in patients without severe EAD (p<0.05), and lowest CRP was 36.7 (28.4–44.9)mg/L in patients with severe EAD against 54.9 (48.7–61.2) in patients without it (p 0.067). Data for this and other related variables are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>A regression model showed age (OR 0.95, 95%IC 0.90–0.99), higher lactate (1.27, 1.04–1.55), APACHE II (1.12, 1.01–1.20) and higher creatinine (3.51, 1.43–8.59) as the only variables with an independent relationship with graft dysfunction, with a Hosmer–Lemeshow goodness of fit of 0.58.AuC data for CRP, lactate, and creatinine at ICU admission against MEAF score (above/below 8 points) is shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>. We compared only the behavior of CRP, lactate, and creatinine because the rest of parameters registered (transaminases, INR, bilirubin) were already included in the MEAF equation. The best cut-off for CRP to detect severe EAD (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>) at ICU admission was 68mg/L (Youden index 0.33), with a sensitivity of 92.3% and a specificity of 40.1%. We computed a power of 99% of our study to detect a statistically significant difference of 33.4mg/L in CRP levels between patients with and without severe EAD.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>We found a negative relationship between CRP levels at ICU admission and in-hospital mortality, observing levels of 59.4 (53.4–65.4)mg/L in survivors vs 24.4 (9.2–39.7) in deceased patients, p<0.01. Lowest CRP levels were 53.9 (48.2–59.7)mg/L in survivors and 24.5 (9.2–39.7) in the deceased, p<0.01].AuC was 0.79 (0.65–0.92) for CRP at ICU admission, and 0.75 (0.60–0.91) for lowest CRP. Results are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> and <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>. A power of 99% was computed to detect a statistically significant difference of 32.24mg/L in CRP levels between patients that did or did not survive.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia>A regression model showed APACHE II (OR 1.34, 95%IC 1.08–1.66), higher lactate (1.42, 1.11–1.82), and CRP at ICU admission (0.95, 0.90–0.99) as the only variables with an independent relationship with mortality, with a Hosmer–Lemeshow goodness of fit of 0.40.DiscussionChanges in serum CRP levels in relation to liver function and more specifically in relation to allograft function after liver transplant is an issue not yet resolved. Our results show that in fact, the liver transplant supposes a significant inflammatory stimulus accompanied by a rise in serum CRP during the postoperative period, but also show how those patients with a worse liver function had lower CRP serum levels and how a lower CRP postoperative increase is independently related to higher mortality. In our patients, a serum level below 68mg/dL on the first postoperative day is a sensible marker (over 92% sensibility) of severe EAD, but with a low specificity (40%), a fact that limits its usefulness.As CRP is a non-specific marker of inflammation synthesized in the liver, its behavior in the setting of a liver transplant is uncertain. On one hand, we should expect CRP to rise because the transplant procedure is itself a strong pro-inflammatory stimulus but on the other hand, a damaged allograft or a retarded normalization of its function, could make it unable to react properly to inflammation, delaying or even aborting CRP production.The role of CRP as a marker of poor graft function after OLT was first proposed by McCormick et al. These investigators, in a series of five liver transplant patients, detected that four of them showed an increase in serum CRP levels and the only patient who failed to show this increase died<a class="elsevierStyleCrossRef" href="#bib0180">13</a> although this finding was challenged by Smith et al.,<a class="elsevierStyleCrossRef" href="#bib0185">14</a> who argued that the CRP measurement method employed could explain this behavior.Other reports as the study from Izumi et al.<a class="elsevierStyleCrossRef" href="#bib0190">15</a> addressing CRP changes after OLT have shown contradictory results. This study demonstrated a significant increment in serum levels in acute (delta=58μ/ml) and chronic liver failure patients (delta=94μ/ml), with a maximum increment in the 4th day after transplant, not related to infection as previous reports had suggested, finally concluding that those changes could be at least in part related to the transplant procedure.A study conducted by Their et al.,<a class="elsevierStyleCrossRef" href="#bib0195">16</a> found an increment in serum CRP values in the postoperative course of liver and kidney transplant in 92% of their patients (median 43mg/L, range 6–130mg/L, maximum peak in the second day and return to normal levels by day 10). 67% of patients with rejection, increased CRP levels (median 52mg/L, range 9–157mg/L) 86% of them returning to normal levels after 5 days of rejection treatment. Also 88% of those patients with bacterial infection had elevated CRP levels (median 85mg/L, range 10–267mg/L). But, when vascular complications occurred, CRP barely rose above normal levels in few patients. Chung et al.<a class="elsevierStyleCrossRef" href="#bib0200">17</a> study the intraoperative decline of CRP after OLT and found that CRP at day 1 after OLT below pre-transplant CRP had a 3-fold increased risk for detrimental outcome.In any case, these results suggest that those patients with liver allograft dysfunction had a reduced peak of CRP compared to those patients complicated with infection, pointing to a diminished inflammatory response when EAD occurs, a hypothesis that seems confirmed by our findings. Kinetics of CRP in the first 3 postoperative days reported in this study coincide with several other studies,<a class="elsevierStyleCrossRefs" href="#bib0190">15,18,19</a> having the maximum peak in day two, but, unlike those studies our data shows that higher levels are attained the first postoperative day.In other scenarios, like liver surgery<a class="elsevierStyleCrossRefs" href="#bib0215">20,21</a> or liver failure plus infection,<a class="elsevierStyleCrossRefs" href="#bib0155">8,22,23</a> low CRP levels have also been associated with liver dysfunction and outcome. Ananian et al.,<a class="elsevierStyleCrossRef" href="#bib0215">20</a> demonstrated that after liver surgery, when acute dysfunction appears, CRP levels have an inverse correlation with hepatic function, a correlation that is maintained during the first month after surgery.Rahman et al.,<a class="elsevierStyleCrossRef" href="#bib0220">21</a> suggested that a blunted rise of CRP after hepatic resection can predict liver dysfunction and reported low CRP levels (28mg/L, 5–119mg/L) after ample liver resection compared to standard (41mg/L, 5–85mg/L) or minimal resections (51mg/L, 8–203mg/L) in the first day after surgery. These findings have been replicated in septic patients<a class="elsevierStyleCrossRef" href="#bib0230">23</a> with liver failure where dampened rise of CRP were related to liver dysfunction rather than the inflammatory process.We must acknowledge some problems with our study, in first place, that our relevant outcome variable, namely severe EAD, is based on clinical and laboratory parameters that in one way or other, mark a group of patients with a poorer outcomes, but is not defined by corresponding pathological findings, that could definitely prove that we are not mixing different problems (ischemia, rejection, allograft dysfunction).Nonetheless, these diagnostic parameters are widely used and eventhough they can generate a selection bias, this is one present in all the studies addressing this topic and consequently do not rest external validity to our results beyond being a single-center study.An additional problem when studying allograft dysfunction is the low incidence of this complication, making the development of larger multicenter studies necessary, to finally define the behavior of CRP in this scenario.In our series, some groups of patients were excluded from the study (acute liver failure) and our decision was motivated because the acute liver failure patients CRP profile can be different from chronic liver disease patients due to different inflammatory stimuli and a deeper liver dysfunction.One aspect that can be challenged in our protocol is the inclusion of a score that was published in the last stages of patients recruitment, namely the MEAF score.<a class="elsevierStyleCrossRef" href="#bib0170">11</a> Even when this decision breaks the integrity of the “prospective” condition of the study, we opted for this strategy because based on reports published this seems a promising diagnostic tool. Even more, in an exploratory study we found this to perform the best in our specific population.<a class="elsevierStyleCrossRef" href="#bib0125">2</a> Besides, all the variables included on this score were already collected prospectively in our study, the laboratory procedures are standardized and have not suffered significant variations during the period of study. Thus, we assumed that this approach did not compromise the validity of our conclusion and the evaluation of this new diagnostic tool adds usefulness to the study.Finally, the number of losses in our population (due to unavailability to determine serum CRP at ICU admission) was high (27.7%) and this fact can suppose a bias in our results, but comparison between excluded and included patients did not show relevant differences (Table 1e shown in supplementary electronic material) and our data are consistent with those few studies previously published elsewhere. Also, the number of patients for the second and third day were diminishing because they died or were discharged to the surgery ward therefore in order to avoid a source of bias, we analyzed only data for CRP at admission and the first day.ConclusionWe conclude that CRP serum levels are high in the early postoperative course after an OLT and a blunted rise in the first postoperative day, with a cut-off of 68mg/L, can be a marker of poor allograft function. Values below this threshold could be used as a screening marker for complications such as early allograft dysfunction. A dampened CRP rise seems to be related to in-hospital mortality in these patients.Grants and financial supportThis work has not received external funding.Authors’ contributionsAll authors participated in writing and revising the paper. H.G.M.E., S.P.G. and B.F.J.E. contributed on design, performance of research, data collection and analysis. Q.G.G., A.R.M.M. and D.R.M.J. contributed on performance of research and data collection.Conflict of interestNone of the authors declare any kind of conflict with the contents of the present manuscript." "textoCompletoSecciones" => array:1 [ "secciones" => array:15 [ 0 => array:3 [ "identificador" => "xres1345912" "titulo" => "Abstract" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Design" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Setting" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Patients" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Variables of interest" ] 5 => array:2 [ "identificador" => "abst0030" "titulo" => "Results" ] 6 => array:2 [ "identificador" => "abst0035" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1238402" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xpalclavsec1238401" "titulo" => "Abbreviations" ] 3 => array:3 [ "identificador" => "xres1345913" "titulo" => "Resumen" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "abst0040" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0045" "titulo" => "Diseño" ] 2 => array:2 [ "identificador" => "abst0050" "titulo" => "Ámbito" ] 3 => array:2 [ "identificador" => "abst0055" "titulo" => "Pacientes" ] 4 => array:2 [ "identificador" => "abst0060" "titulo" => "Variables de interés" ] 5 => array:2 [ "identificador" => "abst0065" "titulo" => "Resultados" ] 6 => array:2 [ "identificador" => "abst0070" "titulo" => "Conclusión" ] ] ] 4 => array:2 [ "identificador" => "xpalclavsec1238400" "titulo" => "Palabras clave" ] 5 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 6 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Setting" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Ethics approval and consent to participate" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Patient information and data collection" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Prior definitions" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Statistical analysis" ] ] ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Results" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0055" "titulo" => "Conclusion" ] 10 => array:2 [ "identificador" => "sec0060" "titulo" => "Grants and financial support" ] 11 => array:2 [ "identificador" => "sec0065" "titulo" => "Authors’ contributions" ] 12 => array:2 [ "identificador" => "sec0070" "titulo" => "Conflict of interest" ] 13 => array:2 [ "identificador" => "xack466041" "titulo" => "Acknowledgments" ] 14 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-12-11" "fechaAceptado" => "2019-02-28" "PalabrasClave" => array:2 [ "en" => array:2 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1238402" "palabras" => array:7 [ 0 => "C-reactive protein" 1 => "Biomarker" 2 => "Early allograft dysfunction" 3 => "Primary graft dysfunction" 4 => "Outcome" 5 => "Postoperative complication" 6 => "Liver function test" ] ] 1 => array:4 [ "clase" => "abr" "titulo" => "Abbreviations" "identificador" => "xpalclavsec1238401" "palabras" => array:13 [ 0 => "ALT" 1 => "APACHE II" 2 => "AST" 3 => "AuC" 4 => "CRP" 5 => "EAD" 6 => "ICU" 7 => "INR" 8 => "MEAF" 9 => "MELD" 10 => "OLT" 11 => "OR" 12 => "ROC" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1238400" "palabras" => array:7 [ 0 => "Proteína C reactiva" 1 => "Biomarcador" 2 => "Disfunción temprana del injerto" 3 => "Disfunción primaria del injerto" 4 => "Resultado" 5 => "Complicación postoperatoria" 6 => "Pruebas de función hepática" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo explore the behavior of C-reactive protein (CRP) after orthotopic liver transplantation (OLT) during the first postoperative days, and its usefulness as a marker of severe early allograft dysfunction (EAD). DesignA prospective, single-center cohort study was carried out. SettingThe Intensive Care Unit (ICU) of a regional hospital with a liver transplant program since 1997. PatientsThe study comprised a total of 183 patients admitted to our ICU immediately after liver transplantation between 2009 and 2015. Variables of interestC-reactive protein levels upon ICU admission and after 24 and 48h, severe EAD and hospital mortality. ResultsThe CRP levels after OLT were: upon ICU admission 57.5 (51.6–63.3)mg/L, after 24h 80.1 (72.9–87.3)mg/L and after 48h 69.9 (62.5–77.4)mg/L. Severe EAD patients (14.2%) had higher mortality (23.1 vs 2.5; OR 11.48: 2.98–44.19) and lower CRP upon ICU admission (39.3 [29.8–48.7]mg/L) than the patients without EAD (0.5 [53.9–67.0]; p<0.05] – the best cut-off point being 68mg/L (sensitivity 92.3%; specificity 40.1%; Youden index 0.33).Lower CRP upon ICU admission was correlated to higher mortality (24.5 [9.2–39.7] vs 59.4 [53.4–65.4]; p<0.01, AUC 0.79 [0.65–0.92]). ConclusionLiver transplant is a strong inflammatory stimulus accompanied by high levels of C-reactive protein. A blunted rise in CRP on the first postoperative day after OLT may be a marker of poor allograft function and is related to hospital mortality." "secciones" => array:7 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Design" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Setting" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Patients" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Variables of interest" ] 5 => array:2 [ "identificador" => "abst0030" "titulo" => "Results" ] 6 => array:2 [ "identificador" => "abst0035" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoExplorar el comportamiento de la proteína C reactiva (PCR) en el postoperatorio inmediato de trasplante hepático y su utilidad como marcador de disfunción grave del injerto hepático. DiseñoEstudio de cohortes prospectivo, unicéntrico. ÁmbitoUnidad de cuidados intensivos (UCI) de un hospital regional. PacientesCiento ochenta y tres pacientes ingresados en nuestra UCI inmediatamente después del trasplante hepático entre 2009-2015. Variables de interésNiveles de PCR al ingreso en UCI, 24 y 48h, disfunción grave del injerto hepático, mortalidad intrahospitalaria. ResultadosLos niveles de PCR en el postoperatorio inmediato de trasplante fueron: al ingreso en UCI 57,5 (51,6-63,3)mg/L, a las 24h 80,1 (72,9-87,3)mg/L y a las 48h 69,9 (62,5-77,4)mg/L. Los pacientes con disfunción grave del injerto (14,2%) tuvieron una mayor mortalidad (23,1 vs. 2,5; OR 11,48: 2,98-44,19) y PCR más baja al ingreso en UCI (39,3 [29,8-48,7]mg/L) que los pacientes sin disfunción grave (0,5 [53,9-67]; p<0,05), siendo el mejor punto de corte para la PCR de 68mg/L (sensibilidad 92,3%; especificidad 40,1%; índice de Youden 0,33).La PCR baja al ingreso tuvo correlación directa con la mortalidad (24,5 [9,2-39,7] vs. 59,4 [53,4-65,4]; p<0,01, AUC 0,79 [0,65-0,92]). ConclusiónEl trasplante hepático es un estímulo inflamatorio intenso que se acompaña de niveles elevados de PCR. Un ascenso truncado de la PCR, en el primer día del postoperatorio de trasplante hepático, puede ser un marcador de funcionamiento inadecuado del injerto hepático y está relacionado con la mortalidad intrahospitalaria." "secciones" => array:7 [ 0 => array:2 [ "identificador" => "abst0040" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0045" "titulo" => "Diseño" ] 2 => array:2 [ "identificador" => "abst0050" "titulo" => "Ámbito" ] 3 => array:2 [ "identificador" => "abst0055" "titulo" => "Pacientes" ] 4 => array:2 [ "identificador" => "abst0060" "titulo" => "Variables de interés" ] 5 => array:2 [ "identificador" => "abst0065" "titulo" => "Resultados" ] 6 => array:2 [ "identificador" => "abst0070" "titulo" => "Conclusión" ] ] ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "The following are the supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0080" ] ] ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1546 "Ancho" => 1583 "Tamanyo" => 121866 ] ] "descripcion" => array:1 [ "en" => "Flow chart of patient's recruitment." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2166 "Ancho" => 1506 "Tamanyo" => 184595 ] ] "descripcion" => array:1 [ "en" => "ROC curve depicting relationship between CRP, lactate and creatinine against graft dysfunction defined as MEAF score >8. AuC: ROC area under curve; CRP: C reactive protein. CRP values depicted as 1/CRP." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 837 "Ancho" => 2083 "Tamanyo" => 83171 ] ] "descripcion" => array:1 [ "en" => "ROC curve depicting relationship between CRP against in-hospital mortality. AuC: ROC area under curve; CRP: C reactive protein. CRP values depicted as 1/CRP." ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "ALT: alanine aminotransferase; AST: aspartate aminotransferase; CRP: C-reactive protein; ICU: Intensive Care Unit; INR: International Normalized Ratio.Data as mean (95% confidence interval for mean)." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">ICU admission \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">24h \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">48h \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Worst value<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n=183 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n=180 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n=155 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CRP (mg/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57.5 (51.6–63.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">80.1 (72.9–87.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">69.9 (62.5–77.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52.3 (46.8–57.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lactate (mmol/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.3 (2–2.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.6 (1.4–1.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.4 (1.1–1.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.7 (2.3–3.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT (IU/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1118 (841–1195) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">987 (833–1141) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">845 (696–993) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1284 (1081–1487) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AST (IU/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1765 (1489–2041) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1383 (1073–1693) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">820 (512–1128) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2237 (1833–2641) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">INR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.02 (1.94–2.11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.77 (1.68–1.85) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.51 (1.45–1.58) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.12 (2.02–2.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bilirubin (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.7 (4.2–5.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.5 (3.1–4.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.3 (2.6–4.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.2 (4.6–5.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Creatinine (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.99 (0.94–1.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.14 (1.07–1.20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.16 (1.07–1.24) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.29 (1.21–1.37) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2309089.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "When more than one determination per day, lowest value for CRP and higher for the rest of variables were analyzed." ] ] ] "descripcion" => array:1 [ "en" => "Daily changes in C-reactive protein and other variables used to monitor liver function after liver transplant." ] ] 4 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "AuC: area under the curve; CRP: C-reactive protein; EAD: early allograft dysfunction; MEAF: Model for Early Allograft Function Scoring; ROC: receiver operating characteristics.Data as the mean (95% confidence interval for the mean) and AuC (95% confidence interval for AuC). Severe EAD=MEAF score >8 points." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No dysfunction (n=157) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Severe EAD (n=26) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ROC AuC \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CRP admission (mg/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60.5 (53.9–67.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39.3 (29.8–48.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.64 (0.54–0.73)<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lower CRP (mg/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54.9 (48.7–61.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36.7 (28.4–44.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ns (0.067) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.61 (0.52–0.71)<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lactate admission (mmol/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.1 (1.9–2.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.6 (2.1–5.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.67 (0.54–0.79) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Worst lactate (mmol/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.4 (2.1–2.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.7 (3.0–6.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.72 (0.60–0.84) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Creatinine admission (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.97 (0.92–1.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.18 (0.94–1.41) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ns \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.59 (0.46–0.72) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Worst creatinine (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.22 (1.15–1.30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.69 (1.47–1.92) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.75 (0.65–0.86) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2309088.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "1/CRP was employed for ROC analysis." ] ] ] "descripcion" => array:1 [ "en" => "Changes in liver function markers in relation to severe EAD." ] ] 5 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "ALT: alanine aminotransferase; AST: aspartate aminotransferase; CRP: C-reactive protein; INR: International Normalized Ratio.Data as the mean (95% confidence interval for the mean)." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Survivors (n=173) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Deceased (n=10) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CRP admission (mg/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59.4 (53.4–65.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.4 (9.2–39.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lower CRP (mg/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53.9 (48.2–59.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.5 (9.2–39.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lactate admission (mmol/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.2 (1.9–2.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.7 (0.9–8.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Worst lactate (mmol/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.4 (2.2–2.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.7 (2.8–10.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT admission (IU/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1012 (831–1192) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1120 (105–2136) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Worst ALT (IU/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1219 (1021–1416) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2409 (897–3921) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ns (0.099) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AST admission (IU/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1734 (1457–2010) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2304 (382–4226) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Worst AST (IU/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2011 (1684–2338) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6146 (1278–11014) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">INR admission \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.98 (1.91–2.06) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.82 (2.16–3.47) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Worst INR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.04 (1.97–2.12) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.46 (2.50–4.42) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bilirubin admission (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.7 (4.1–5.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.3 (3.2–7.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Worst Bilirubin (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.2 (4.5–5.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.2 (4.2–8.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ns (0.068) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Creatinine admission (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.98 (0.93–1.04) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.25 (0.83–1.67) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ns (0.083) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Worst creatinine (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.27 (1.19–1.35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.66 (1.32–1.99) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2309090.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Changes in liver function markers in relation to in-hospital mortality." ] ] 6 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.pdf" "ficheroTamanyo" => 18921 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:23 [ 0 => array:3 [ "identificador" => "bib0120" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Postoperative complications of liver transplantation: relationship with mortality" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "G. Seller-Pérez" 1 => "M.E. Herrera-Gutiérrez" 2 => "R. Aragonés-Manzanares" 3 => "A. Muñoz-López" 4 => "M. Lebrón-Gallardo" 5 => "J. Antonio González-Correa" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Med Clin (Barc)" "fecha" => "2004" "volumen" => "123" "paginaInicial" => "321" "paginaFinal" => "327" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0125" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early graft dysfunction after liver transplant: comparison of different diagnostic criteria in a single-center prospective cohort" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J.E. Barrueco-Francioni" 1 => "G. Seller-Pérez" 2 => "R. Lozano-Saéz" 3 => "M.D. Arias-Verdú" 4 => "G. Quesada-García" 5 => "M.E. 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"vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/21735727/0000004400000005/v1_202006090711/S2173572720300990/v1_202006090711/en/main.assets" "Apartado" => array:4 [ "identificador" => "411" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735727/0000004400000005/v1_202006090711/S2173572720300990/v1_202006090711/en/main.pdf?idApp=WMIE&text.app=https://medintensiva.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572720300990?idApp=WMIE"]

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C-reactive protein at ICU admission as a marker of early graft dysfunction after liver transplant. A prospective, single-center cohort study

Proteína C reactiva al ingreso en UCI como marcador de disfunción temprana del injerto tras trasplante hepático. Estudio unicéntrico, prospectivo y de cohortes

G. Seller-Péreza, J.E. Barrueco-Francionia,c, R. Lozano-Sáeza, M.M. Arrebola-Ramírezb, M.J. Diez-de-los-Ríosb, G. Quesada-Garcíaa, M.E. Herrera-Gutiérreza,c,

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mehguci@gmail.com

Corresponding author.

a Intensive Care Medicine Unit, Regional University Hospital of Malaga, Spain

b Clinical Analysis Department, Regional University Hospital of Malaga, Spain

c Faculty of Medicine, Universidad de Málaga, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Orthotopic liver transplantation &#40;OLT&#41; is the main treatment for patients with a severe liver disease&#44; but this is a complex surgical procedure and subject to a high number of complications&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">1</span></a> An important issue in the management of these patients is the evaluation of the function of the implanted organ but&#44; considering the wide spectrum of functions performed by the liver&#44; its assessment is not easy to undertake&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Markers for cytolysis&#44; biliary production&#44; ammonia&#44; lactate and coagulation factors synthesized by the liver are widely used for the assessment of graft function&#44; but there is no clear agreement about how and when to use them&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">2&#44;3</span></a> In this scenario&#44; the identification of other useful parameters for the evaluation of graft function could potentially hasten the detection of severe early allograft dysfunction &#40;EAD&#41; and help to initiate measures to diminish its intensity or even halt its development&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Many tests have been proposed to increment the array of tools at our disposal such as the rate of elimination of molecules cleared by the liver &#40;i&#46;e&#46; indocyanine green or C-methacetin&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">4&#8211;6</span></a> or a change in serum levels of different inflammatory markers&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">C-reactive protein &#40;CRP&#41; is an acute phase reactant<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">7</span></a> synthesized mainly by the liver&#44; and its synthesis initiates about 6<span class="elsevierStyleHsp" style=""></span>h after an inflammatory insult&#44; with exponential increments every 8<span class="elsevierStyleHsp" style=""></span>h&#44; until its maximal peak 50<span class="elsevierStyleHsp" style=""></span>h after the insult&#46; Surgical procedures such as OLT are known to induce inflammation&#44; therefore&#44; an increase of CRP should be expected&#46; Nonetheless&#44; bearing in mind the role of the liver in its synthesis&#44; disturbances in hepatic function should result in a dampened increase in CRP serum level&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">8</span></a> Accordingly&#44; CRP production will depend on one hand on the impact of the inflammatory stimulus of the surgery and on the other hand on the functional capability of the allograft&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">8</span></a> For this reason&#44; we hypothesize that when liver allograft function is altered&#44; CRP production is blunted&#44; and recognizing this will help the early detection of severe allograft dysfunction&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">9</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Study design</span><p id="par0025" class="elsevierStylePara elsevierViewall">We conducted a prospective&#44; single center&#44; cohort study&#44; registering a series of consecutive OLT recipient patients admitted to our intensive care unit &#40;ICU&#41; from February 2009 to February 2015&#46; For the design of the study and the preparation of the manuscript&#44; we adhered to the recommendations of the STROBE initiative &#40;Strengthening the Reporting of Observational Studies in Epidemiology&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Setting</span><p id="par0030" class="elsevierStylePara elsevierViewall">The ICU of the Regional University Hospital in Malaga&#44; Spain&#46; During the period covered by this study &#40;2009&#8211;2015&#41; all patients were managed according to an institutional hospital protocol covering all phases of the transplant process &#40;preoperative&#44; operative and postoperative stages&#41; that was maintained without substantial changes&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Our protocol includes the use of the piggy-back technique and end to end anastomosis of the common bile duct in most cases&#44; immediate postoperative care in our ICU for all patients&#44; and clear indications for the immunosuppressive strategy&#58; calcineurin inhibitors plus steroids &#40;the most frequently used&#41;&#44; mammalian target of rapamycin inhibitors plus steroids or interleukin 2 receptor antibodies plus steroids according to patient&#39;s characteristics and past medical history&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Ethics approval and consent to participate</span><p id="par0040" class="elsevierStylePara elsevierViewall">This study was compliant with the principles of the Declaration of Helsinki and Good Clinical Practice Guidelines and approved by the Committee for Ethics in Research of the Regional University Hospital of Malaga&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Informed consent was obtained on admission to the ICU by either the patient or next of kin&#46; Confidentiality was assured by registering variables in a disaggregated database&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Patient information and data collection</span><p id="par0050" class="elsevierStylePara elsevierViewall">Recruitment was conducted between February 2009 and February 2015&#46; A flow-chart of study recruitment is presented in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46; Patients admitted to the ICU for postoperative care after OLT that complied with the study protocol &#40;samples of CRP could be taken at ICU admission and at 24 and 48<span class="elsevierStyleHsp" style=""></span>h and did not present exclusion criteria&#41; were enrolled in the study&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Exclusion criteria&#58; age less than 18 years&#44; emergent OLT after acute liver failure&#44; clinical and microbiological evidence of active infection&#44; and refusal from the patient or his&#47;her representative to participate in the study&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">As per institutional hospital protocol&#44; serum lactate&#44; transaminases&#44; INR&#44; bilirubin&#44; and creatinine are measured on admission to the ICU after the liver transplant and every 12<span class="elsevierStyleHsp" style=""></span>h until discharge from the unit&#46; Plasma CRP was additionally measured at ICU admission&#44; 24 and 48<span class="elsevierStyleHsp" style=""></span>h&#46; A quantitative method based on polystyrene coated monoclonal antibodies against CRP was used &#40;Dimension Vista 1500 System&#174;&#41;&#46; This test detects CRP concentrations in a range of 2&#46;9&#8211;190<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Prior definitions</span><p id="par0065" class="elsevierStylePara elsevierViewall">Severe dysfunction of liver allograft was defined using the MEAF &#40;Model for Early Allograft Function Scoring&#41; score<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">11</span></a> with a cut-off over 8 points&#46; This score is calculated by an equation comprising of three markers usually measured to evaluate liver function&#58; ALT&#44; INR&#44; and total bilirubin&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The MEAF score was developed when recruitment was closing but due to the fact that all the required variables were already registered prospectively in our database&#44; the statistical analysis was not due to be performed until the end of the recruiting period and in our population we found that this score performs better&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">2</span></a> we opted for its inclusion in the study&#46; The primary outcome was severe graft dysfunction by MEAF score and the secondary outcome was in-hospital mortality&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Statistical analysis</span><p id="par0075" class="elsevierStylePara elsevierViewall">As a first step&#44; normality was probed with the Kolmogorov&#8211;Smirnov test&#44; detecting that variables following a normal distribution were&#58; MELD &#40;Model for End-Stage Liver Disease&#41;&#44; MEAF and CRP in days 1 and 3&#46; Despite this fact and for the sake of readability of results&#44; the mean and confidence interval of the mean were selected for the description of those continuous variables in which this parameter was more informative than the median&#46; For the rest of variables&#44; the median and interquartile range are the statistics shown&#46; Categorical variables are presented as percentages&#46; Chi-square&#44; <span class="elsevierStyleItalic">U</span>-Mann Whitney&#44; and Kruskal&#8211;Wallis tests were applied with a <span class="elsevierStyleItalic">p</span>-value &#60;0&#46;05&#46; Corresponding Odds Ratio &#40;OR&#41; and 95&#37; confidence interval of OR are shown when applicable&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Being a prospective cohort and not having information about the standard deviation of CRP in these populations we were not able to calculate beforehand the sample size needed so we calculated the power of our results&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">To determine optimal cut-off level of CRP for detection of severe allograft dysfunction&#44; a receiver operating characteristics &#40;ROC&#41; curve was drawn&#44; its correspondent area under the curve &#40;AuC&#41; &#40;95&#37; confidence interval&#41; calculated&#44; and the Youden Index used to define the best cut-off point&#46; In order to show an upward ROC curve&#44; to simplify visual understanding of the results&#44; 1&#47;CRP was employed to draw the curve&#44; after performing all calculations with raw CRP values&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">In order to test a relationship between CRP and outcome&#44; a model of logistic regression was computed by the backward conditional stepwise method&#44; including all variables with a statistical relationship below 0&#46;15 &#40;sex&#44; age&#44; chronic kidney disease&#44; previous OLT&#44; MELD previous to OLT&#44; APACHE II&#44; higher lactate&#44; creatinine at admission&#44; higher creatinine and CRP at admission&#41; in the univariate analysis and severe EAD or in-hospital mortality as the dependent variable&#59; these results are presented as OR &#40;95&#37; confidence interval&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">For statistical analysis and creation of figures the statistical package R 3&#46;1&#46;2 for OsX&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">12</span></a> and Prism 6 for Mac Os X &#40;GraphPad Software Inc&#174;&#41; were employed&#46; In order to compute the power of our study we used the Statmate 2&#174; for Windows software&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Results</span><p id="par0100" class="elsevierStylePara elsevierViewall">Of 272 patients admitted after OLT&#44; none showed clinical or microbiological signs of infection and 19 had acute liver disease&#46; 253 patients did not show exclusion criteria&#44; among them&#44; a valid determination of CRP was performed at ICU admission in 183 patients &#40;180 at 24 and 155 at 48<span class="elsevierStyleHsp" style=""></span>h respectively&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Mean age was 54&#46;3 &#40;52&#46;8&#8211;55&#46;7&#41; years and 45 &#40;24&#46;6&#37;&#41; of our patients were female&#46; Model for End-Stage Liver Disease &#40;MELD&#41; score before OLT was 16&#46;5 &#40;15&#46;5&#8211;17&#46;6&#41; points and mean APACHE II at ICU admission was 14&#46;4 &#40;13&#46;8&#8211;15&#46;1&#41;&#46; Arterial hypertension in 47 &#40;25&#46;7&#37;&#41;&#44; diabetes in 47 &#40;25&#46;7&#37;&#41; and chronic renal disease in 15 &#40;8&#46;2&#37;&#41; were registered as relevant comorbidities&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Main indications for OLT were&#58; alcoholic liver disease in 87 &#40;47&#46;5&#37;&#41;&#44; chronic viral hepatitis in 51 &#40;27&#46;9&#37;&#41;&#44; biliary tree diseases in 16 &#40;8&#46;7&#37;&#41;&#44; cryptogenic 12 &#40;6&#46;6&#37;&#41;&#44; and other 9&#46;3&#37;&#46; Thirteen patients &#40;7&#46;1&#37;&#41; had a previous OLT&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Median hospital stay before surgery was 1 &#40;interquartile range 0&#8211;1&#41; day&#44; median ICU length of stay 3 &#40;3&#8211;5&#41; days&#44; and total hospital length of stay 12 &#40;9&#8211;20&#41; days&#46; In-hospital mortality was 10 cases &#40;5&#46;5&#37;&#41;&#44; 8 out of 183 &#40;4&#46;4&#37;&#41; in the early postoperative course during ICU stay and 2 out of 175 &#40;1&#46;1&#37;&#41; in the hospital ward after ICU discharge&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Mean CRP at ICU admission 57&#46;5 &#40;51&#46;6&#8211;63&#46;3&#41;<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; at 24<span class="elsevierStyleHsp" style=""></span>h 80&#46;1 &#40;72&#46;9&#8211;87&#46;3&#41;<span class="elsevierStyleHsp" style=""></span>mg&#47;L and at 48<span class="elsevierStyleHsp" style=""></span>h 69&#46;9 &#40;62&#46;5&#8211;77&#46;4&#41;<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#46; Mean lower value for CRP 52&#46;3 &#40;46&#46;8&#8211;57&#46;9&#41;<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#46; Concentration of CRP and classic markers of liver function are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">Twenty-six &#40;14&#46;2&#37;&#41; patients were diagnosed with severe EAD &#40;MEAF score &#62;8&#41; and had higher mortality &#40;23&#46;1&#37; vs 2&#46;5&#37;&#59; OR 11&#46;48 &#91;95&#37; CI 2&#46;98&#8211;44&#46;19&#93;&#41;&#46; CRP at ICU admission was 39&#46;3 &#40;29&#46;8&#8211;48&#46;7&#41;<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; against 60&#46;5 &#40;53&#46;9&#8211;67&#46;0&#41;<span class="elsevierStyleHsp" style=""></span>mg&#47;L in patients without severe EAD &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; and lowest CRP was 36&#46;7 &#40;28&#46;4&#8211;44&#46;9&#41;<span class="elsevierStyleHsp" style=""></span>mg&#47;L in patients with severe EAD against 54&#46;9 &#40;48&#46;7&#8211;61&#46;2&#41; in patients without it &#40;<span class="elsevierStyleItalic">p</span> 0&#46;067&#41;&#46; Data for this and other related variables are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">A regression model showed age &#40;OR 0&#46;95&#44; 95&#37;IC 0&#46;90&#8211;0&#46;99&#41;&#44; higher lactate &#40;1&#46;27&#44; 1&#46;04&#8211;1&#46;55&#41;&#44; APACHE II &#40;1&#46;12&#44; 1&#46;01&#8211;1&#46;20&#41; and higher creatinine &#40;3&#46;51&#44; 1&#46;43&#8211;8&#46;59&#41; as the only variables with an independent relationship with graft dysfunction&#44; with a Hosmer&#8211;Lemeshow goodness of fit of 0&#46;58&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">AuC data for CRP&#44; lactate&#44; and creatinine at ICU admission against MEAF score &#40;above&#47;below 8 points&#41; is shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#46; We compared only the behavior of CRP&#44; lactate&#44; and creatinine because the rest of parameters registered &#40;transaminases&#44; INR&#44; bilirubin&#41; were already included in the MEAF equation&#46; The best cut-off for CRP to detect severe EAD &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; at ICU admission was 68<span class="elsevierStyleHsp" style=""></span>mg&#47;L &#40;Youden index 0&#46;33&#41;&#44; with a sensitivity of 92&#46;3&#37; and a specificity of 40&#46;1&#37;&#46; We computed a power of 99&#37; of our study to detect a statistically significant difference of 33&#46;4<span class="elsevierStyleHsp" style=""></span>mg&#47;L in CRP levels between patients with and without severe EAD&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">We found a negative relationship between CRP levels at ICU admission and in-hospital mortality&#44; observing levels of 59&#46;4 &#40;53&#46;4&#8211;65&#46;4&#41;<span class="elsevierStyleHsp" style=""></span>mg&#47;L in survivors vs 24&#46;4 &#40;9&#46;2&#8211;39&#46;7&#41; in deceased patients&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#46; Lowest CRP levels were 53&#46;9 &#40;48&#46;2&#8211;59&#46;7&#41;<span class="elsevierStyleHsp" style=""></span>mg&#47;L in survivors and 24&#46;5 &#40;9&#46;2&#8211;39&#46;7&#41; in the deceased&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#93;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">AuC was 0&#46;79 &#40;0&#46;65&#8211;0&#46;92&#41; for CRP at ICU admission&#44; and 0&#46;75 &#40;0&#46;60&#8211;0&#46;91&#41; for lowest CRP&#46; Results are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> and <a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#46; A power of 99&#37; was computed to detect a statistically significant difference of 32&#46;24<span class="elsevierStyleHsp" style=""></span>mg&#47;L in CRP levels between patients that did or did not survive&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">A regression model showed APACHE II &#40;OR 1&#46;34&#44; 95&#37;IC 1&#46;08&#8211;1&#46;66&#41;&#44; higher lactate &#40;1&#46;42&#44; 1&#46;11&#8211;1&#46;82&#41;&#44; and CRP at ICU admission &#40;0&#46;95&#44; 0&#46;90&#8211;0&#46;99&#41; as the only variables with an independent relationship with mortality&#44; with a Hosmer&#8211;Lemeshow goodness of fit of 0&#46;40&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Discussion</span><p id="par0155" class="elsevierStylePara elsevierViewall">Changes in serum CRP levels in relation to liver function and more specifically in relation to allograft function after liver transplant is an issue not yet resolved&#46; Our results show that in fact&#44; the liver transplant supposes a significant inflammatory stimulus accompanied by a rise in serum CRP during the postoperative period&#44; but also show how those patients with a worse liver function had lower CRP serum levels and how a lower CRP postoperative increase is independently related to higher mortality&#46; In our patients&#44; a serum level below 68<span class="elsevierStyleHsp" style=""></span>mg&#47;dL on the first postoperative day is a sensible marker &#40;over 92&#37; sensibility&#41; of severe EAD&#44; but with a low specificity &#40;40&#37;&#41;&#44; a fact that limits its usefulness&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">As CRP is a non-specific marker of inflammation synthesized in the liver&#44; its behavior in the setting of a liver transplant is uncertain&#46; On one hand&#44; we should expect CRP to rise because the transplant procedure is itself a strong pro-inflammatory stimulus but on the other hand&#44; a damaged allograft or a retarded normalization of its function&#44; could make it unable to react properly to inflammation&#44; delaying or even aborting CRP production&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The role of CRP as a marker of poor graft function after OLT was first proposed by McCormick et al&#46; These investigators&#44; in a series of five liver transplant patients&#44; detected that four of them showed an increase in serum CRP levels and the only patient who failed to show this increase died<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">13</span></a> although this finding was challenged by Smith et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">14</span></a> who argued that the CRP measurement method employed could explain this behavior&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Other reports as the study from Izumi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">15</span></a> addressing CRP changes after OLT have shown contradictory results&#46; This study demonstrated a significant increment in serum levels in acute &#40;delta<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>58<span class="elsevierStyleHsp" style=""></span>&#956;&#47;ml&#41; and chronic liver failure patients &#40;delta<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>94<span class="elsevierStyleHsp" style=""></span>&#956;&#47;ml&#41;&#44; with a maximum increment in the 4th day after transplant&#44; not related to infection as previous reports had suggested&#44; finally concluding that those changes could be at least in part related to the transplant procedure&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">A study conducted by Their et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">16</span></a> found an increment in serum CRP values in the postoperative course of liver and kidney transplant in 92&#37; of their patients &#40;median 43<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; range 6&#8211;130<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; maximum peak in the second day and return to normal levels by day 10&#41;&#46; 67&#37; of patients with rejection&#44; increased CRP levels &#40;median 52<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; range 9&#8211;157<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41; 86&#37; of them returning to normal levels after 5 days of rejection treatment&#46; Also 88&#37; of those patients with bacterial infection had elevated CRP levels &#40;median 85<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; range 10&#8211;267<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41;&#46; But&#44; when vascular complications occurred&#44; CRP barely rose above normal levels in few patients&#46; Chung et al&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">17</span></a> study the intraoperative decline of CRP after OLT and found that CRP at day 1 after OLT below pre-transplant CRP had a 3-fold increased risk for detrimental outcome&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">In any case&#44; these results suggest that those patients with liver allograft dysfunction had a reduced peak of CRP compared to those patients complicated with infection&#44; pointing to a diminished inflammatory response when EAD occurs&#44; a hypothesis that seems confirmed by our findings&#46; Kinetics of CRP in the first 3 postoperative days reported in this study coincide with several other studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">15&#44;18&#44;19</span></a> having the maximum peak in day two&#44; but&#44; unlike those studies our data shows that higher levels are attained the first postoperative day&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">In other scenarios&#44; like liver surgery<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">20&#44;21</span></a> or liver failure plus infection&#44;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">8&#44;22&#44;23</span></a> low CRP levels have also been associated with liver dysfunction and outcome&#46; Ananian et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">20</span></a> demonstrated that after liver surgery&#44; when acute dysfunction appears&#44; CRP levels have an inverse correlation with hepatic function&#44; a correlation that is maintained during the first month after surgery&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Rahman et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">21</span></a> suggested that a blunted rise of CRP after hepatic resection can predict liver dysfunction and reported low CRP levels &#40;28<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; 5&#8211;119<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41; after ample liver resection compared to standard &#40;41<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; 5&#8211;85<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41; or minimal resections &#40;51<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; 8&#8211;203<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41; in the first day after surgery&#46; These findings have been replicated in septic patients<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">23</span></a> with liver failure where dampened rise of CRP were related to liver dysfunction rather than the inflammatory process&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">We must acknowledge some problems with our study&#44; in first place&#44; that our relevant outcome variable&#44; namely severe EAD&#44; is based on clinical and laboratory parameters that in one way or other&#44; mark a group of patients with <span class="elsevierStyleCrossOut">a</span> poorer outcomes&#44; but is not defined by corresponding pathological findings&#44; that could definitely prove that we are not mixing different problems &#40;ischemia&#44; rejection&#44; allograft dysfunction&#41;&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Nonetheless&#44; these diagnostic parameters are widely used and eventhough they can generate a selection bias&#44; this is one present in all the studies addressing this topic and consequently do not rest external validity to our results beyond being a single-center study&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">An additional problem when studying allograft dysfunction is the low incidence of this complication&#44; making the development of larger multicenter studies necessary&#44; to finally define the behavior of CRP in this scenario&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">In our series&#44; some groups of patients were excluded from the study &#40;acute liver failure&#41; and our decision was motivated because the acute liver failure patients CRP profile can be different from chronic liver disease patients due to different inflammatory stimuli and a deeper liver dysfunction&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">One aspect that can be challenged in our protocol is the inclusion of a score that was published in the last stages of patients recruitment&#44; namely the MEAF score&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">11</span></a> Even when this decision breaks the integrity of the &#8220;prospective&#8221; condition of the study&#44; we opted for this strategy because based on reports published this seems a promising diagnostic tool&#46; Even more&#44; in an exploratory study we found this to perform the best in our specific population&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">2</span></a> Besides&#44; all the variables included on this score were already collected prospectively in our study&#44; the laboratory procedures are standardized and have not suffered significant variations during the period of study&#46; Thus&#44; we assumed that this approach did not compromise the validity of our conclusion and the evaluation of this new diagnostic tool adds usefulness to the study&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Finally&#44; the number of losses in our population &#40;due to unavailability to determine serum CRP at ICU admission&#41; was high &#40;27&#46;7&#37;&#41; and this fact can suppose a bias in our results&#44; but comparison between excluded and included patients did not show relevant differences &#40;Table 1e shown in supplementary electronic material&#41; and our data are consistent with those few studies previously published elsewhere&#46; Also&#44; the number of patients for the second and third day were diminishing because they died or were discharged to the surgery ward therefore in order to avoid a source of bias&#44; we analyzed only data for CRP at admission and the first day&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conclusion</span><p id="par0225" class="elsevierStylePara elsevierViewall">We conclude that CRP serum levels are high in the early postoperative course after an OLT and a blunted rise in the first postoperative day&#44; with a cut-off of 68<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; can be a marker of poor allograft function&#46; Values below this threshold could be used as a screening marker for complications such as early allograft dysfunction&#46; A dampened CRP rise seems to be related to in-hospital mortality in these patients&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Grants and financial support</span><p id="par0230" class="elsevierStylePara elsevierViewall">This work has not received external funding&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Authors&#8217; contributions</span><p id="par0235" class="elsevierStylePara elsevierViewall">All authors participated in writing and revising the paper&#46; H&#46;G&#46;M&#46;E&#46;&#44; S&#46;P&#46;G&#46; and B&#46;F&#46;J&#46;E&#46; contributed on design&#44; performance of research&#44; data collection and analysis&#46; Q&#46;G&#46;G&#46;&#44; A&#46;R&#46;M&#46;M&#46; and D&#46;R&#46;M&#46;J&#46; contributed on performance of research and data collection&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Conflict of interest</span><p id="par0240" class="elsevierStylePara elsevierViewall">None of the authors declare any kind of conflict with the contents of the present manuscript&#46;</p></span></span>"
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            0 => "C-reactive protein"
            1 => "Biomarker"
            2 => "Early allograft dysfunction"
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          "clase" => "keyword"
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          "identificador" => "xpalclavsec1238400"
          "palabras" => array:7 [
            0 => "Prote&#237;na C reactiva"
            1 => "Biomarcador"
            2 => "Disfunci&#243;n temprana del injerto"
            3 => "Disfunci&#243;n primaria del injerto"
            4 => "Resultado"
            5 => "Complicaci&#243;n postoperatoria"
            6 => "Pruebas de funci&#243;n hep&#225;tica"
          ]
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To explore the behavior of C-reactive protein &#40;CRP&#41; after orthotopic liver transplantation &#40;OLT&#41; during the first postoperative days&#44; and its usefulness as a marker of severe early allograft dysfunction &#40;EAD&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Design</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A prospective&#44; single-center cohort study was carried out&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Setting</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The Intensive Care Unit &#40;ICU&#41; of a regional hospital with a liver transplant program since 1997&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Patients</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The study comprised a total of 183 patients admitted to our ICU immediately after liver transplantation between 2009 and 2015&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Variables of interest</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">C-reactive protein levels upon ICU admission and after 24 and 48<span class="elsevierStyleHsp" style=""></span>h&#44; severe EAD and hospital mortality&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Results</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">The CRP levels after OLT were&#58; upon ICU admission 57&#46;5 &#40;51&#46;6&#8211;63&#46;3&#41;<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; after 24<span class="elsevierStyleHsp" style=""></span>h 80&#46;1 &#40;72&#46;9&#8211;87&#46;3&#41;<span class="elsevierStyleHsp" style=""></span>mg&#47;L and after 48<span class="elsevierStyleHsp" style=""></span>h 69&#46;9 &#40;62&#46;5&#8211;77&#46;4&#41;<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#46; Severe EAD patients &#40;14&#46;2&#37;&#41; had higher mortality &#40;23&#46;1 vs 2&#46;5&#59; OR 11&#46;48&#58; 2&#46;98&#8211;44&#46;19&#41; and lower CRP upon ICU admission &#40;39&#46;3 &#91;29&#46;8&#8211;48&#46;7&#93;<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41; than the patients without EAD &#40;0&#46;5 &#91;53&#46;9&#8211;67&#46;0&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#93; &#8211; the best cut-off point being 68<span class="elsevierStyleHsp" style=""></span>mg&#47;L &#40;sensitivity 92&#46;3&#37;&#59; specificity 40&#46;1&#37;&#59; Youden index 0&#46;33&#41;&#46;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Lower CRP upon ICU admission was correlated to higher mortality &#40;24&#46;5 &#91;9&#46;2&#8211;39&#46;7&#93; vs 59&#46;4 &#91;53&#46;4&#8211;65&#46;4&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#44; AUC 0&#46;79 &#91;0&#46;65&#8211;0&#46;92&#93;&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusion</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Liver transplant is a strong inflammatory stimulus accompanied by high levels of C-reactive protein&#46; A blunted rise in CRP on the first postoperative day after OLT may be a marker of poor allograft function and is related to hospital mortality&#46;</p></span>"
        "secciones" => array:7 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Design"
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            "identificador" => "abst0015"
            "titulo" => "Setting"
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            "identificador" => "abst0025"
            "titulo" => "Variables of interest"
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        "resumen" => "<span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Objetivo</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Explorar el comportamiento de la prote&#237;na C reactiva &#40;PCR&#41; en el postoperatorio inmediato de trasplante hep&#225;tico y su utilidad como marcador de disfunci&#243;n grave del injerto hep&#225;tico&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Dise&#241;o</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Estudio de cohortes prospectivo&#44; unic&#233;ntrico&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">&#193;mbito</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Unidad de cuidados intensivos &#40;UCI&#41; de un hospital regional&#46;</p></span> <span id="abst0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Pacientes</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Ciento ochenta y tres pacientes ingresados en nuestra UCI inmediatamente despu&#233;s del trasplante hep&#225;tico entre 2009-2015&#46;</p></span> <span id="abst0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Variables de inter&#233;s</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Niveles de PCR al ingreso en UCI&#44; 24 y 48<span class="elsevierStyleHsp" style=""></span>h&#44; disfunci&#243;n grave del injerto hep&#225;tico&#44; mortalidad intrahospitalaria&#46;</p></span> <span id="abst0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Resultados</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Los niveles de PCR en el postoperatorio inmediato de trasplante fueron&#58; al ingreso en UCI 57&#44;5 &#40;51&#44;6-63&#44;3&#41;<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; a las 24<span class="elsevierStyleHsp" style=""></span>h 80&#44;1 &#40;72&#44;9-87&#44;3&#41;<span class="elsevierStyleHsp" style=""></span>mg&#47;L y a las 48<span class="elsevierStyleHsp" style=""></span>h 69&#44;9 &#40;62&#44;5-77&#44;4&#41;<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#46; Los pacientes con disfunci&#243;n grave del injerto &#40;14&#44;2&#37;&#41; tuvieron una mayor mortalidad &#40;23&#44;1 vs&#46; 2&#44;5&#59; OR 11&#44;48&#58; 2&#44;98-44&#44;19&#41; y PCR m&#225;s baja al ingreso en UCI &#40;39&#44;3 &#91;29&#44;8-48&#44;7&#93;<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41; que los pacientes sin disfunci&#243;n grave &#40;0&#44;5 &#91;53&#44;9-67&#93;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#44; siendo el mejor punto de corte para la PCR de 68<span class="elsevierStyleHsp" style=""></span>mg&#47;L &#40;sensibilidad 92&#44;3&#37;&#59; especificidad 40&#44;1&#37;&#59; &#237;ndice de Youden 0&#44;33&#41;&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">La PCR baja al ingreso tuvo correlaci&#243;n directa con la mortalidad &#40;24&#44;5 &#91;9&#44;2-39&#44;7&#93; vs&#46; 59&#44;4 &#91;53&#44;4-65&#44;4&#93;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#44; AUC 0&#44;79 &#91;0&#44;65-0&#44;92&#93;&#41;&#46;</p></span> <span id="abst0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conclusi&#243;n</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">El trasplante hep&#225;tico es un est&#237;mulo inflamatorio intenso que se acompa&#241;a de niveles elevados de PCR&#46; Un ascenso truncado de la PCR&#44; en el primer d&#237;a del postoperatorio de trasplante hep&#225;tico&#44; puede ser un marcador de funcionamiento inadecuado del injerto hep&#225;tico y est&#225; relacionado con la mortalidad intrahospitalaria&#46;</p></span>"
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            "identificador" => "abst0040"
            "titulo" => "Objetivo"
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            "identificador" => "abst0045"
            "titulo" => "Dise&#241;o"
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          2 => array:2 [
            "identificador" => "abst0050"
            "titulo" => "&#193;mbito"
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          3 => array:2 [
            "identificador" => "abst0055"
            "titulo" => "Pacientes"
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          4 => array:2 [
            "identificador" => "abst0060"
            "titulo" => "Variables de inter&#233;s"
          ]
          5 => array:2 [
            "identificador" => "abst0065"
            "titulo" => "Resultados"
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            "identificador" => "abst0070"
            "titulo" => "Conclusi&#243;n"
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            "apendice" => "<p id="par0255" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0080"
          ]
        ]
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      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1546
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            "Tamanyo" => 121866
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Flow chart of patient&#39;s recruitment&#46;</p>"
        ]
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      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 2166
            "Ancho" => 1506
            "Tamanyo" => 184595
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">ROC curve depicting relationship between CRP&#44; lactate and creatinine against graft dysfunction defined as MEAF score &#62;<span class="elsevierStyleHsp" style=""></span>8&#46; AuC&#58; ROC area under curve&#59; CRP&#58; C reactive protein&#46; CRP values depicted as 1&#47;CRP&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 837
            "Ancho" => 2083
            "Tamanyo" => 83171
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">ROC curve depicting relationship between CRP against in-hospital mortality&#46; AuC&#58; ROC area under curve&#59; CRP&#58; C reactive protein&#46; CRP values depicted as 1&#47;CRP&#46;</p>"
        ]
      ]
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          "leyenda" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">ALT&#58; alanine aminotransferase&#59; AST&#58; aspartate aminotransferase&#59; CRP&#58; C-reactive protein&#59; ICU&#58; Intensive Care Unit&#59; INR&#58; International Normalized Ratio&#46;</p><p id="spar0145" class="elsevierStyleSimplePara elsevierViewall">Data as mean &#40;95&#37; confidence interval for mean&#41;&#46;</p>"
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                  \t\t\t\t" scope="col">ICU admission&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1284 &#40;1081&#8211;1487&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">AST &#40;IU&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">1765 &#40;1489&#8211;2041&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1383 &#40;1073&#8211;1693&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">820 &#40;512&#8211;1128&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2237 &#40;1833&#8211;2641&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">INR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;02 &#40;1&#46;94&#8211;2&#46;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;77 &#40;1&#46;68&#8211;1&#46;85&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;51 &#40;1&#46;45&#8211;1&#46;58&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;12 &#40;2&#46;02&#8211;2&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bilirubin &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;7 &#40;4&#46;2&#8211;5&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;5 &#40;3&#46;1&#8211;4&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;3 &#40;2&#46;6&#8211;4&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;2 &#40;4&#46;6&#8211;5&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Creatinine &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;99 &#40;0&#46;94&#8211;1&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;14 &#40;1&#46;07&#8211;1&#46;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;16 &#40;1&#46;07&#8211;1&#46;24&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;29 &#40;1&#46;21&#8211;1&#46;37&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">AuC&#58; area under the curve&#59; CRP&#58; C-reactive protein&#59; EAD&#58; early allograft dysfunction&#59; MEAF&#58; Model for Early Allograft Function Scoring&#59; ROC&#58; receiver operating characteristics&#46;</p><p id="spar0150" class="elsevierStyleSimplePara elsevierViewall">Data as the mean &#40;95&#37; confidence interval for the mean&#41; and AuC &#40;95&#37; confidence interval for AuC&#41;&#46; Severe EAD<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>MEAF score &#62;8 points&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No dysfunction &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>157&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Severe EAD &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>26&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ROC AuC&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">CRP admission &#40;mg&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#46;5 &#40;53&#46;9&#8211;67&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#46;3 &#40;29&#46;8&#8211;48&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;64 &#40;0&#46;54&#8211;0&#46;73&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lower CRP &#40;mg&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&#46;9 &#40;48&#46;7&#8211;61&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&#46;7 &#40;28&#46;4&#8211;44&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ns &#40;0&#46;067&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;61 &#40;0&#46;52&#8211;0&#46;71&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lactate admission &#40;mmol&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;1 &#40;1&#46;9&#8211;2&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;6 &#40;2&#46;1&#8211;5&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;67 &#40;0&#46;54&#8211;0&#46;79&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Worst lactate &#40;mmol&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;4 &#40;2&#46;1&#8211;2&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;7 &#40;3&#46;0&#8211;6&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;72 &#40;0&#46;60&#8211;0&#46;84&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Creatinine admission &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;97 &#40;0&#46;92&#8211;1&#46;02&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;18 &#40;0&#46;94&#8211;1&#46;41&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;59 &#40;0&#46;46&#8211;0&#46;72&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Worst creatinine &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;22 &#40;1&#46;15&#8211;1&#46;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;69 &#40;1&#46;47&#8211;1&#46;92&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;75 &#40;0&#46;65&#8211;0&#46;86&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "leyenda" => "<p id="spar0135" class="elsevierStyleSimplePara elsevierViewall">ALT&#58; alanine aminotransferase&#59; AST&#58; aspartate aminotransferase&#59; CRP&#58; C-reactive protein&#59; INR&#58; International Normalized Ratio&#46;</p><p id="spar0155" class="elsevierStyleSimplePara elsevierViewall">Data as the mean &#40;95&#37; confidence interval for the mean&#41;&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Survivors &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>173&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Deceased &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">CRP admission &#40;mg&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&#46;4 &#40;53&#46;4&#8211;65&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#46;4 &#40;9&#46;2&#8211;39&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#60;0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Lower CRP &#40;mg&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&#46;9 &#40;48&#46;2&#8211;59&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#46;5 &#40;9&#46;2&#8211;39&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lactate admission &#40;mmol&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;2 &#40;1&#46;9&#8211;2&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;7 &#40;0&#46;9&#8211;8&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Worst lactate &#40;mmol&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;4 &#40;2&#46;2&#8211;2&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;7 &#40;2&#46;8&#8211;10&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#60;0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ALT admission &#40;IU&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1012 &#40;831&#8211;1192&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1120 &#40;105&#8211;2136&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Worst ALT &#40;IU&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1219 &#40;1021&#8211;1416&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2409 &#40;897&#8211;3921&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ns &#40;0&#46;099&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AST admission &#40;IU&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1734 &#40;1457&#8211;2010&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2304 &#40;382&#8211;4226&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Worst AST &#40;IU&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2011 &#40;1684&#8211;2338&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6146 &#40;1278&#8211;11014&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">INR admission&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;98 &#40;1&#46;91&#8211;2&#46;06&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;82 &#40;2&#46;16&#8211;3&#46;47&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Worst INR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;04 &#40;1&#46;97&#8211;2&#46;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;46 &#40;2&#46;50&#8211;4&#46;42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bilirubin admission &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;7 &#40;4&#46;1&#8211;5&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;3 &#40;3&#46;2&#8211;7&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Worst Bilirubin &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;2 &#40;4&#46;5&#8211;5&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;2 &#40;4&#46;2&#8211;8&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ns &#40;0&#46;068&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Creatinine admission &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;98 &#40;0&#46;93&#8211;1&#46;04&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;25 &#40;0&#46;83&#8211;1&#46;67&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ns &#40;0&#46;083&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Worst creatinine &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;27 &#40;1&#46;19&#8211;1&#46;35&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;66 &#40;1&#46;32&#8211;1&#46;99&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0130" class="elsevierStyleSimplePara elsevierViewall">Changes in liver function markers in relation to in-hospital mortality&#46;</p>"
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Article information

ISSN: 21735727
Original language: English

DOI:10.1016/j.medine.2019.02.013

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	4	3	7
2024 October	57	39	96
2024 September	53	72	125
2024 August	79	37	116
2024 July	93	29	122
2024 June	58	42	100
2024 May	52	40	92
2024 April	49	41	90
2024 March	31	25	56
2024 February	29	44	73
2024 January	43	25	68
2023 December	38	30	68
2023 November	41	43	84
2023 October	27	30	57
2023 September	24	39	63
2023 August	19	15	34
2023 July	30	30	60
2023 June	23	22	45
2023 May	39	55	94
2023 April	40	19	59
2023 March	69	35	104
2023 February	55	24	79
2023 January	76	19	95
2022 December	87	37	124
2022 November	81	44	125
2022 October	135	32	167
2022 September	92	33	125
2022 August	102	37	139
2022 July	82	31	113
2022 June	36	34	70
2022 May	64	29	93
2022 April	54	39	93
2022 March	86	60	146
2022 February	57	26	83
2022 January	95	37	132
2021 December	60	45	105
2021 November	71	36	107
2021 October	131	80	211
2021 September	125	35	160
2021 August	97	40	137
2021 July	55	32	87
2021 June	66	27	93
2021 May	107	46	153
2021 April	198	83	281
2021 March	81	25	106
2021 February	76	25	101
2021 January	58	23	81
2020 December	40	32	72
2020 November	24	17	41
2020 October	8	5	13
2020 July	59	17	76
2020 June	78	15	93

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