A multivariable prediction model for intra-amniotic infection in patients with preterm labor and intact membranes including a point of care system that measures amniotic fluid MMP-8.

OBJECTIVES: Among patients with preterm labor and intact membranes (PTL), those with intra-amniotic infection (IAI) present the highest risk of adverse perinatal outcomes. Current identification of IAI, based on microbiological cultures and/or polymerase chain reaction amplification of the 16S ribosomal RNA gene, delay diagnosis and, consequently, antenatal management. The aim to of the study was to assess the performance of a multivariable prediction model for diagnosing IAI in patients with PTL below 34.0 weeks using clinical, sonographic and biochemical biomarkers. METHODS: From 2019 to 2022, we prospectively included pregnant patients admitted below 34.0 weeks with diagnosis of PTL and had undergone amniocentesis to rule in/out IAI. The main outcome was IAI, defined by a positive culture and/or 16S ribosomal RNA gene in amniotic fluid. Based on the date of admission, the sample (n=98) was divided into a derivation (2019-2020, n=49) and validation cohort (2021-2022, n=49). Logistic regression models were developed for the outcomes evaluated. As predictive variables we explored ultrasound cervical length measurement at admission, maternal C-reactive protein, gestational age, and amniotic fluid glucose and matrix metalloproteinase-8 (MMP-8) levels. The model was developed in the derivation cohort and applied to the validation cohort and diagnostic performance was evaluated. Clinical management was blinded to the model results. RESULTS: During the study period, we included 98 patients admitted with a diagnosis of PTL. Of these, 10 % had IAI. The final model included MMP-8 and amniotic fluid glucose levels and showed an area under the receiver operating characteristic curve to predict the risk of IAI of 0.961 (95 % confidence interval: 0.860-0.995) with a sensitivity of 75 %, specificity of 93.3 %, positive likelihood ratio (LR) of 11.3 and negative LR of 0.27 in the validation cohort. CONCLUSIONS: In patients with PTL, a multivariable prediction model including amniotic fluid MMP-8 and glucose levels might help in the clinical management of patients undergoing amniocentesis to rule in/out IAI, providing results within a few minutes.

Performance evaluation of the high sensitive troponin I assay on the Atellica IM analyser.

Introduction: The Fourth Universal Definition of Myocardial Infarction Global Taskforce recommends the use of high sensitive troponin (hs-Tn) assays in the diagnosis of acute myocardial infarction. We evaluated the analytical performance of the Atellica IM High-sensitivity Troponin I Assay (hs-TnI) (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) and compared its performance to other hs-TnI assays (Siemens Advia Centaur, Dimension Vista, Dimension EXL, and Abbott Architect (Wiesbaden, Germany)) at one or more sites across Europe. Materials and methods: Precision, detection limit, linearity, method comparison, and interference studies were performed according to Clinical and Laboratory Standards Institute protocols. Values in 40 healthy individuals were compared to the manufacturer's cut-offs. Sample turnaround time (TAT) was examined. Results: Imprecision repeatability CVs were 1.1-4.7% and within-lab imprecision were 1.8-7.6% (10.0-25,000 ng/L). The limit of blank (LoB), detection (LoD), and quantitation (LoQ) aligned with the manufacturer's values of 0.5 ng/L, 1.6 ng/L, and 2.5 ng/L, respectively. Passing-Bablok regression demonstrated good correlations between Atellica IM analyser with other systems; some minor deviations were observed. All results in healthy volunteers fell below the 99th percentile URL, and greater than 50% of each sex demonstrated values above the LoD. No interference was observed for biotin (≤ 1500 µg/L), but a slight bias at 5.0 g/L haemoglobin and 50 ng/L Tn was observed. TAT from was fast (mean time = 10.9 minutes) and reproducible (6%CV). Conclusions: Real-world analytical and TAT performance of the hs-TnI assay on the Atellica IM analyser make this assay fit for routine use in clinical laboratories.

The loss of DHX15 impairs endothelial energy metabolism, lymphatic drainage and tumor metastasis in mice.

DHX15 is a downstream substrate for Akt1, which is involved in key cellular processes affecting vascular biology. Here, we explored the vascular regulatory function of DHX15. Homozygous DHX15 gene deficiency was lethal in mouse and zebrafish embryos. DHX15-/- zebrafish also showed downregulation of VEGF-C and reduced formation of lymphatic structures during development. DHX15+/- mice depicted lower vascular density and impaired lymphatic function postnatally. RNAseq and proteome analysis of DHX15 silenced endothelial cells revealed differential expression of genes involved in the metabolism of ATP biosynthesis. The validation of these results demonstrated a lower activity of the Complex I in the mitochondrial membrane of endothelial cells, resulting in lower intracellular ATP production and lower oxygen consumption. After injection of syngeneic LLC1 tumor cells, DHX15+/- mice showed partially inhibited primary tumor growth and reduced lung metastasis. Our results revealed an important role of DHX15 in vascular physiology and pave a new way to explore its potential use as a therapeutical target for metastasis treatment.

Value of clinical laboratory test for early prediction of mortality in patients with COVID-19: the BGM score.

BACKGROUND: COVID-19 causes high mortality and long hospitalization periods. The aim of this study was to search for new early prognostic strategies accessible to most health care centers. METHODS: Laboratory results, demographic and clinical data from 500 patients with positive SARS-CoV-2 infection were included in our study. The data set was split into training and test set prior to generating different multivariate models considering the occurrence of death as the response variable. A final computational method called the BGM score was obtained by combining the previous models and is available as an interactive web application. RESULTS: The logistic regression model comprising age, creatinine (CREA), D-dimer (DD), C-reactive protein (CRP), platelet count (PLT), and troponin I (TNI) showed a sensitivity of 47.3%, a specificity of 98.7%, a kappa of 0.56, and a balanced accuracy of 0.73. The CART classification tree yielded TNI, age, DD, and CRP as the most potent early predictors of mortality (sensitivity = 68.4%, specificity = 92.5%, kappa = 0.61, and balanced accuracy = 0.80). The artificial neural network including age, CREA, DD, CRP, PLT, and TNI yielded a sensitivity of 66.7%, a specificity of 92.3%, a kappa of 0.54, and a balanced accuracy of 0.79. Finally, the BGM score surpassed the prediction accuracy performance of the independent multivariate models, yielding a sensitivity of 73.7%, a specificity of 96.5%, a kappa of 0.74, and a balanced accuracy of 0.85. CONCLUSIONS: The BGM score may support clinicians in managing COVID-19 patients and providing focused interventions to those with an increased risk of mortality.

Tetracaine from urethral ointment causes false positive amphetamine results by immunoassay.

BACKGROUND: Amphetamine urine drug screening by immunoassay is prone to cross-react with other compounds leading to false positive results. Tetracaine is a local anesthetic drug used in the clinical setting as an ointment during urinary catheterization. In our laboratory, tetracaine is often detected by gas chromatography-mass spectrometry in the urine of patients admitted in the emergency department with false positive amphetamine results. The objectives of this study were to investigate if there was cross-reactivity to tetracaine in an amphetamine immunoassay and to retrospectively evaluate the potential contribution of tetracaine to false positive amphetamine results. METHODS: An interference study was conducted using negative urine samples spiked with increasing concentrations of tetracaine hydrochloride and analyzed with the CEDIA Amphetamine/Ecstasy immunoassay. Retrospectively, urine samples of patients which yielded positive amphetamine immunoassay results and were analyzed by gas chromatography-mass spectrometry were reviewed (n = 417). The presence of tetracaine and/or other drugs by gas chromatography-mass spectrometry were gathered. RESULTS: Tetracaine caused false positive amphetamine results by immunoassay (cut-off 1000 µg/L) with a concentration of above 40 mg/L. Retrospective analysis of all positive amphetamine immunoassay samples showed that in 45 out of the 417 (10.8%) urine samples no amphetamine-like derivative was identified by gas chromatography - mass spectrometry. In 37 out of 45 (82.2%) of these false positive cases tetracaine was detected, of whom 59.5% (22/37) had an estimated tetracaine concentration of ≥40 mg/L. CONCLUSIONS: This study confirmed the interference of tetracaine in the CEDIA Amphetamine/Ecstasy immunoassay and that tetracaine may have contributed to around 80% of the false positive amphetamine cases in the urine samples of patients admitted to the emergency department at our institution.

Evaluation of an immunoassay procedure to measure 6-monoacetylmorphine.

Introduction: 6-Monoacetylmorphine (6-MAM) is a specific metabolite of heroin. Thus, the presence of 6-MAM in urine is a definitive indication of heroin intake. The possibility of having an immunoassay procedure to measure 6-MAM would be a diagnosis tool to discriminate, among opiates-positive, those patients who have consumed heroin and those who have not.Methods: EMIT® II Plus 6-Acetylmorphine Assay was used to measure 6-MAM in urine. The positive opiate screening results were confirmed at the Toxicology laboratory of our hospital by GC-MS.Results: This study includes 63 urine samples from subjects admitted to emergency department with suspicion of opiate consumption. Specificity was evaluated in the two groups of samples studied. In the first group all samples which resulted negative by opiate immunoassay (n = 33) were negative for 6-MAM immunoassay test. Thus, the specificity obtained for 6-MAM immunoassay in this group was 100%. Regarding the second specificity study, performed in positive samples by opiate immunoassay which were negative to 6 MAM by GC-MS, the specificity decreased down to 75%. In the study of sensitivity all samples confirmed as positive to 6-MAM by confirmatory method (GC-MS) resulted positive by the screening method, thus sensitivity obtained was 100%.Discussion: In this study no FN for 6-MAM was observed and therefore the new Emit® II Plus 6- Acetylmorphine Assay procedure has a high NPV, thus a negative result with 6-MAM immunoassay practically excludes heroine consume. The positive results to 6-MAM by immunoassay should be confirmed by a more analytically specific method, such as GCMS.

Cerium oxide nanoparticles display antilipogenic effect in rats with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, ranging from steatosis to non-alcoholic steatohepatitis (NASH). Recently, cerium oxide nanoparticles (CeO2NPs) have emerged as a new antioxidant agent with hepatoprotective properties in experimental liver disease. The aim of the current investigation was to elucidate whether CeO2NPs display beneficial effects in an experimental model of NAFLD.Therefore, fifteen Wistar rats were subjected to a methionine and choline deficient diet (MCDD) for 6 weeks and intravenously treated with CeO2NP or vehicle during the weeks three and four of the diet. The effect of CeO2NPs on serum biochemistry, hepatic steatosis, inflammation, fatty acid content and expression of reactive oxygen species (ROS) and lipid metabolism related genes was assessed. MCDD fed rats showed increased inflammation, enhanced hepatic lipid accumulation of both saturated and unsaturated fatty acids (FAs) and overexpression of genes related to fatty liver and ROS metabolism. Treatment with CeO2NPs was able to reduce the size and content of hepatocyte lipid droplets, the hepatic concentration of triglyceride- and cholesterol ester-derived FAs and the expression of several genes involved in cytokine, adipokine and chemokine signaling pathways. These findings suggest that CeO2NPs could be of beneficial value in NAFLD.

Procedimiento para la interpretación de un cambio entre dos valores consecutivos de una magnitud biológica / Procedure for the interpretation of a change between two consecutive values of a biological quantity

Los intervalos de referencia biológicos no proporcionan información suficiente para la interpretación de un cambio entre dos valores medidos consecutivos debido a que, para la gran mayoría de las magnitudes, la variabilidad biológica intraindividual es menor que la variabilidad biológica interindividual. Teniendo en cuenta esta situación, el laboratorio podría proporcionar, conjuntamente con los intervalos de referencia, información adicional que permita estimar de manera objetiva la significación de un cambio en los valores de una magnitud biológica para un mismo individuo. En este sentido, la manera más adecuada para interpretar un cambio debe realizarse en función del concepto de incertidumbre, ya que permite considerar todas las posibles fuentes de variación a las que están sometidos los valores medidos. Este documento, basado en guías de ámbito nacional e internacional se describe un procedimiento para la interpretación de un cambio entre dos valores consecutivos de una magnitud biológica, basado en el estudio de las diversas fuentes de incertidumbre que le afectan

Biological reference intervals do not provide sufficient information for the interpretation of a change between two consecutive measured values of a biological quantity because, for the vast majority of quantities, the intra-individual biological variability is smaller than the inter-individual biological variability. Taking into account this situation, the laboratory could provide, in conjunction with the reference intervals, additional information to objectively estimate the significance of a change in the values of a biological quantity. In this sense, the most adequate way to interpret the change must be made on the basis of the uncertainty concept, since it allows taking into account all the possible sources of variation to which the measured values are subjected. This document, based on national and international guidelines, describes a procedure for the interpretation of a change between two consecutive values of a biological quantity, based on the study of the various sources of uncertainty that affect it

Análisis bioquímico como método eficiente para aumentar la seguridad de la nutrición parenteral en neonatos / Biochemical test as an efficient system to improve safety in parenteral nutrition for premature infants

Objetivo: Se describe el proceso de validación del control bioquímico de las bolsas de nutrición parenteral para verificar la correcta composición de ingredientes críticos antes de la administración, así como su impacto en la seguridad tras dos años desde la implantación en una población de recién nacidos prematuros. Método: Para la validación de la técnica se usaron 35 muestras de nutrición parenteral sin lípidos, que se procesaron en el laboratorio de Urgencias, siguiendo los procedimientos rutinarios utilizados para medir las concentraciones de glucosa y electrolitos en plasma y orina. Para analizar su impacto en la seguridad se realizaron análisis pre y post implantación mediante análisis modal de falla, efectos y criticidad. También se evaluaron los resultados fuera de rango y sus potenciales repercusiones en la seguridad del paciente. Resultados: El análisis de regresión no muestra error sistemático de medida para glucosa, calcio y potasio; en cambio, para el sodio y el magnesio sí existe un error sistemático, por lo que ambos fueron descartados para los análisis rutinarios. Los resultados del análisis modal de fallos y efectos, atribuibles a la implantación del control bioquímico, mostraron una disminución del riesgo del proceso del 11%. Se analizaron 1.734 nutriciones, correspondientes a 218 neonatos prematuros; se encontraron 58 (3,3%) resultados fuera del rango de aceptación, de los cuales 7 se consideraron errores de preparación potencialmente peligrosos. Conclusiones: El control bioquímico de glucosa y electrolitos es un método eficiente y reproducible que evita que posibles errores de preparación afecten al paciente

Objective: The biochemical test validation process of parenteral nutrition bags is described to verify the correct composition of critical compounds before its administration, as well as its impact on safety after two years since its implantation in a population of premature infants. Method: For the validation of the technique, 35 samples of parenteral nutrition without lipids were processed by the emergency laboratory, following the routine procedures used to measure the concentrations of glucose and electrolytes in plasma and urine. To analyze its impact on safety, pre-implantation and post-implantation risk analysis was carried out using failure mode, effects and criticality analysis (FMECA). Likewise, all out-of-range results and their potential repercussions on patient safety were evaluated. Results: Regression analysis showed no systematic measurement error for glucose, calcium and potassium; however, there is a constant systematic error for sodium and magnesium, thus both were discarded for routine analysis. Failure mode, effects and criticality analysis results showed a decrease in the risk of the process of 11% for the biochemical test. We tested 1,734 parenteral nutritions from 218 premature neonates; 58 (3.3%) results were out of the acceptance range, and 7 were considered to be potentially dangerous compounding errors. Conclusions: The biochemical test of glucose and electrolytes is an efficient and reproducible method that prevents possible compounding errors from reaching the patient

Biochemical test as an efficient system to improve safety in parenteral nutrition for premature infants.

OBJECTIVE: The biochemical test validation process of parenteral nutrition bags  is described to verify the correct composition of critical compounds before its  administration, as well as its impact on safety after two years since its  implantation in a population of premature infants. METHOD: For the validation of the technique, 35 samples of parenteral nutrition  without lipids were processed by the emergency laboratory, following the routine procedures used to measure the concentrations of glucose and electrolytes in  plasma and urine. To analyze its impact on safety, pre-implantation and post- implantation risk analysis was carried out using failure mode, effects and  criticality analysis (FMECA). Likewise, all out-of-range results and their potential  repercussions on patient safety were evaluated. RESULTS: Regression analysis showed no systematic measurement error for  glucose, calcium and potassium; however, there is a constant systematic error  for sodium and magnesium, thus both were discarded for routine analysis.  Failure mode, effects and criticality analysis results showed a decrease in the  risk of the process of 11% for the biochemical test. We tested 1,734 parenteral  nutritions from 218 premature neonates; 58 (3.3%) results were out of the  acceptance range, and 7 were considered to be potentially dangerous  compounding errors. CONCLUSIONS: The biochemical test of glucose and electrolytes is an efficient and reproducible method that prevents possible compounding errors from reaching  the patient.

Objetivo: Se describe el proceso de validación del control bioquímico de las  bolsas de nutrición parenteral para verificar la correcta composición de  ingredientes críticos antes de la administración, así como su impacto en la  seguridad tras dos años desde la implantación en una población de recién  nacidos prematuros.Método: Para la validación de la técnica se usaron 35 muestras de nutrición  parenteral sin lípidos, que se procesaron en el laboratorio de Urgencias,  siguiendo los procedimientos rutinarios utilizados para medir las concentraciones  de glucosa y electrolitos en plasma y orina. Para analizar su  impacto en la seguridad se realizaron análisis pre y post implantación mediante  análisis modal de falla, efectos y criticidad. También se evaluaron los resultados  fuera de rango y sus potenciales repercusiones en la seguridad del paciente.Resultados: El análisis de regresión no muestra error sistemático de medida  para glucosa, calcio y potasio; en cambio, para el sodio y el magnesio sí existe  un error sistemático, por lo que ambos fueron descartados para los análisis  rutinarios. Los resultados del análisis modal de fallos y efectos, atribuibles a la  implantación del control bioquímico, mostraron una disminución del riesgo del  proceso del 11%. Se analizaron 1.734 nutriciones, correspondientes a 218  neonatos prematuros; se encontraron 58 (3,3%) resultados fuera del rango de  aceptación, de los cuales 7 se consideraron errores de preparación  potencialmente peligrosos.Conclusiones: El control bioquímico de glucosa y electrolitos es un método  eficiente y reproducible que evita que posibles errores de preparación afecten al  paciente.

Desarrollo de procedimientos de medida basados en la cromatografía líquida de alta resolución / Development of measurement procedures based on high-performance liquid chromatography

No disponible

Procedimiento para el estudio de interferencias exógenas en la medición de magnitudes biológicas. Documento técnico (2017) / Procedure for the study of exogenous interferences in the measurement of biological quantities. Technical document (2017)

No disponible

Nomenclatura y unidades de las propiedades biológicas. Recomendación (2016) / Nomenclature and units of biological properties. Recommendation (2016)

No disponible

Validación de procedimientos de medida basados en la cromatografía líquida de alta resolución / Validation of measurement procedures based on high-performance liquid chromatography

No disponible

Recomendaciones sobre la evaluación de las prestaciones técnicas de un glucómetro. Recomendación (2016) / Recommendations for assessing the technical features of a glucometer. Recommendation (2016)

No disponible

Procedimiento para la transferencia y revisión de intervalos de referencia biológicos / Procedure for transference and review of biological reference intervals

No disponible

The GALA study: relationship between galectin-3 serum levels and short- and long-term outcomes of patients with acute heart failure.

OBJECTIVE: We tested the hypothesis that early measurement of galectin-3 at the emergency department (ED) during an episode of acute heart failure (AHF) allows predicting short- and long-term outcomes. METHODS: We performed an exploratory study including 115 patients consecutively diagnosed with AHF in a single ED. Clinical and analytical variables were recorded. The primary endpoint was 30-day all-cause mortality, and secondary endpoints were 30-day composite outcome (death, rehospitalization or ED reconsultation, whichever first) and 1-year mortality. RESULTS: Seven patients (6.1%) died within 30 days and 43 (37.4%) within 1 year. The 30-day composite endpoint was observed in 21.1% of patients. Galectin-3 was correlated with NT-proBNP and the glomerular filtration rate but not with age and s-cTnI. Measured at time of ED arrival, galectin-3 showed good discriminatory capacity for 30-day mortality (AUC ROC: 0.732; 95% CI 0.512-0.953; p = 0.041) but not for 1-year mortality (0.521; 0.408-0.633; p = 0.722). Patients with galectin-3 concentrations >42 µg/L had an OR = 7.67(95%CI = 1.57-37.53; p = 0.012) for 30-day mortality. Conversely, NT-proBNP only showed predictive capacity for 1-year mortality (0.642; 0.537-0.748; p = 0.014). Patients with NT-proBNP concentrations >5400 ng/L had an OR = 4.34 (95%CI = 1.93-9.77; p < 0.001) for 1-year mortality. These increased short- (galectin-3) and long-term (NT-proBNP) risks remained significant after adjustment for age or renal function. s-cTnI failed in both short- and long term death prediction. No biomarker predicted the short-term composite endpoint. CONCLUSION: These results suggest that galectin-3 could help to monitor the risk of short-term mortality in unselected patients with AHF attended in the ED.

Prognostic value of plasma apelin concentrations at admission in patients with ST-segment elevation acute myocardial infarction.

BACKGROUND: The use of plasma biomarkers is relevant for the prognosis of ST-segment elevation myocardial infarction (STEMI) patients. Apelin, an adipocytokine, plays a pivotal role in the pathophysiology of both ischemia/reperfusion injury and its potential subsequent heart failure. We evaluated apelin concentrations at admission as a biomarker to assess risk of 6-month mortality. METHODS: Consecutive patients with STEMI were recruited from January 2012 to January 2013 (n=250). Plasma apelin, brain natriuretic peptide (BNP) and sensitive troponin I (sTnI) were assessed in EDTA-plasma samples obtained at admission. Clinical, hemodynamic and other laboratory variables were also registered. All-cause mortality was assessed at 6-month follow-up. RESULTS: Increased plasma apelin concentrations at admission were predictive of 6- month mortality, after adjustment for age, diabetes, systolic blood pressure, heart rate, glomerular filtration rate, Killip class, left ventricular ejection fraction, BNP and sTnI. The combination of apelin with BNP and sTnI further improved the apelin predictive value. Finally, apelin concentrations were associated with markers of ischemic heart failure severity, but not with markers of ischemic insult severity. CONCLUSIONS: Increased plasma concentrations of apelin at admission in patients with STEMI were associated with a higher risk of mortality at 6months, adding prognostic value to the provided by BNP. Moreover, apelin levels were also related to markers of ischemic heart failure severity, but not markers of ischemia severity.

Verificación e implantación en un laboratorio de urgencias de un sistema de medición de los índices séricos (hemólisis, ictericia y lipidemia) en un Dimension® EXL(TM) / Verification and implementation of a serum index measurement system (haemolysis, icterus, and lipaemia) in a Dimension® EXL(TM) in an emergency laboratory

Introducción. La hemólisis, ictericia y lipidemia son los principales interferentes que pueden producir errores analíticos en la medición de magnitudes bioquímicas. Muchos analizadores incorporan sistemas de detección de interferentes, sin embargo no suelen estar verificados. El objetivo del estudio es verificar el sistema de medición HIL del analizador Dimension® EXL(TM) y comprobar la adecuada asignación por el proveedor de los valores de alerta. Material y métodos. Se ha evaluado el efecto de la hemoglobina, bilirrubina y triglicéridos en los resultados, comparando el valor de la magnitud en la muestra sin interferente con los valores obtenidos en la misma muestra con concentraciones crecientes del mismo. Se ha seguido el procedimiento recomendado por la Comisión de Metrología y Sistemas Analíticos de la SEQC. Asimismo, se ha elaborado un algoritmo de cuándo informar la presencia de interferencias (criterios clínicos y técnicos). Resultados. Todos los resultados de los índices hemolíticos incluyeron la concentración esperada del interferente, para la ictericia hubo ligeras diferencias, mientras que para la lipidemia el analizador proporcionó resultados más bajos de los esperados. En el estudio de los índices de alerta HIL hubo diferencias entre los resultados obtenidos y la información del fabricante. Se presenta el algoritmo para informar la presencia de estas interferencias. Conclusiones. La incorporación de estos índices de alerta sin una previa verificación de los mismos puede llevar a cometer errores. Una correcta verificación de estos sistemas permitiría detectar la falta de veracidad en la medición de estos interferentes o el inadecuado establecimiento de algunos índices de alerta (AU)

Introduction. Haemolysis, icterus (bilirubin) and lipaemia (triglycerides) (HIL) are the main interferences that can lead to analytical errors in the measurement of biological substances. Many analysers incorporate interference detection systems, which nonetheless are often not verified. The main objective is to verify the HIL measurement system of the Dimension® EXL(TM) analyser, and to check the correct assignment of the alert values by the supplier. Material and methods. The effect of the haemolysis, bilirubin and triglycerides on the results has been assessed by comparing the value of the quantity in a sample without interference with the values obtained in the same sample with increasing concentrations of interfering substances. The procedure recommended by the Comisión de Metrología y Sistemas Analíticos of the SEQC has been followed. An algorithm to inform of interferences, based on clinical and technical aspects, has been developed. Results. All haemolytic index results included the expected concentration of the interfering substance. Few errors were found for icterus, while for lipaemia the analyser gave results lower than expected. In the study of the HIL alert indexes, differences were found between the results obtained and the information provided by the supplier. Finally the algorithm followed in our laboratory to inform the presence of interfering substances is presented. Conclusions. The introduction of these alert indexes without a prior verification of them can lead to potential errors. Proper verification of these systems would enable detecting the lack of trueness in the measurement of the interfering substances or the inadequate establishment of some alert indexes (AU)

Cerium oxide nanoparticles reduce steatosis, portal hypertension and display anti-inflammatory properties in rats with liver fibrosis.

BACKGROUND & AIMS: Cerium oxide nanoparticles (CeO2NPs) have proven to behave as free radical scavengers and/or anti-inflammatory agents. The aim of the study was to determine whether CeO2NPs display hepatoprotective properties in experimental chronic liver disease. METHODS: Systemic and hepatic effects of nanoparticles were assessed in CCl4-treated rats receiving CeO2NPs or vehicle twice weekly for two weeks and CCl4 treatment was continued for 8 additional weeks. Thereafter, mean arterial pressure and portal pressure (PP) were assessed and serum samples obtained to measure standard hepatic and renal function tests. Organ and subcellular distribution of NPs were assessed using mass spectrometry (ICP-MS) and transmission electron microscopy. Liver samples were obtained to evaluate steatosis, α-SMA expression, macrophage infiltration, apoptosis and mRNA expression of oxidative stress, inflammatory or vasoactive related genes. RESULTS: Most CeO2NPs were located in the liver and it reduced hepatic steatosis, ameliorated systemic inflammatory biomarkers and improved PP without affecting mean arterial pressure. In addition, a marked reduction in mRNA expression of inflammatory cytokines (TNFα, IL1ß, COX-2, iNOS), ET-1 and messengers related to oxidative (Epx, Ncf1, Ncf2) or endoplasmic reticulum (Atf3, Hspa5) stress signaling pathways was observed in the liver of rats receiving CeO2NPs. This was associated with reduced macrophage infiltration and reduced abundance of caspase-3, α-SMA and inflammatory cytokines. CONCLUSIONS: CeO2NPs administration to CCl4-treated rats protects against chronic liver injury by reducing liver steatosis and portal hypertension and markedly attenuating the intensity of the inflammatory response, thereby suggesting that CeO2NPs may be of therapeutic value in chronic liver disease.