Quality assurance of add-on testing in plasma samples: stability limit for 29 biochemical analytes.

Introduction: Clinical laboratories should guarantee sample stability in specific storage conditions for further analysis. The aim of this study is to evaluate the stability of plasma samples under refrigeration for 29 common biochemical analytes usually ordered within an emergency context, in order to determine the maximum allowable period for conducting add-on testing. Materials and methods: A total of 20 patient samples were collected in lithium heparin tubes without gel separator. All analyses were performed using Alinity systems (Abbott Laboratories, Abbott Park, USA) and samples were stored at 2-8 °C. Measurements were conducted in primary plasma tubes at specific time points up to 48 hours, with an additional stability study in plasma aliquots extending the time storage up to 96 hours. The stability limit was estimated considering the total limit of change criteria. Results: Of the 29 studied parameters, 24 demonstrated stabilities within a 48-hour storage period in primary plasma tubes. However, five analytes: aspartate aminotransferase, glucose, lactate dehydrogenase, inorganic phosphate and potassium evidenced instability at different time points (7.9 hours, 2.7 hours, 2.9 hours, 6.2 hours and 4.7 hours, respectively). The stability study in plasma aliquots showed that all parameters remained stable for 96 hours, except lactate dehydrogenase, with a stability limit of 63 hours. Conclusions: A reduced stability of primary plasma samples was observed for five common biochemical analytes ordered in an emergency context. To ensure the quality of add-on testing for these samples, plasma aliquots provide stability for a longer period.

Periodic verification of results' comparability between several analyzers: experience in the application of the EP31-A-IR guideline.

OBJECTIVES: To assess the usefulness of the EP31-A-IR guideline published by the Clinical and Laboratory Standards Institute (CLSI) to perform the periodic verification of results' comparability between several analyzers. METHODS: Twenty-four biochemistry parameters that could be measured in different analyzers were included: albumin, alkaline phosphatase, alanine aminotransferase, amylase, aspartate aminotransferase, calcium, chloride, C-reactive protein, creatine kinase, creatinine, direct bilirubin, gamma glutamyl transferase, glucose, lactate dehydrogenase, magnesium, phosphate, potassium, sodium, total bilirubin, total cholesterol, total protein, triglycerides, urea and uric acid. In accordance with the EP31-A-IR guideline: (1) Patient samples were selected considering the concentration or activity of interest. (2) Acceptance criteria were established specifically for each concentration or activity level. A quality specification based on biological variation or on state of the art was selected, considering the analytical performance of the available technology. (3) Maximum allowable differences (MAD) between analyzers were calculated. (4) Measurements were performed as stated in appendix B of the guideline. (5) Maximum differences between analyzers were calculated. Results were considered comparable when the maximum difference was less than or equal to the MAD. RESULTS: For the 24 parameters evaluated, any difference between analyzers exceeded the MAD. CONCLUSIONS: The EP31-A-IR guideline proved to be useful for periodic verification of results' comparability. However, it must be considered that, to be practicable, it may require to adjust the acceptance criteria in accordance to the analytical performance of the available technology; as well as the number of analytical measurements conforming to the laboratory resources.

Characterization of add-on testing before and after automation at a core laboratory.

Objectives: Add-on testing refers to the process that occurs in clinical laboratories when clinicians request that additional tests be performed on a previously analysed specimen. This is a common but inefficient procedure, highly time-consuming, especially at core laboratories and could be optimised by automating these procedures. The aims of this study are: 1) To describe patterns of add-on testing at a core laboratory at a tertiary hospital, 2) To evaluate turnaround time (TAT) before and after automation of the pre-, post- and analytical phases. Methods: Retrospective, observational study conducted at the biochemistry area of a core laboratory of all add-on orders received in two different months (pre-automation and post-automation). Results: A total of 2464 add-on orders were analysed, representing around 5 % of total requests. Most orders were for either one (>50 %) or two (≈20 %) tests. Most orders were received during the week (from Monday to Friday), particularly during the morning shift (>50 %). More than 50 % of requests were made by the Emergency Department. The two most common add-on parameters were C-reactive protein and N-terminal pro-brain natriuretic peptide. After automation, the median TAT decreased by 42.3 % (from 52 to 22 min). The largest decreases in TAT were observed for routine samples (58.89 %) and fully automated analyses (56.86 %). Conclusions: Automation of our core laboratory substantially reduced turnaround time for add-on testing, indicating an increase in efficiency. Automation eliminated several manual steps in the process, leading to a mean reduction of 15 work hours per day (more than 2 full-time equivalents).

Cost-effectiveness of a high-sensitivity cardiac troponin T systematic screening strategy compared with usual care to identify patients with peri-operative myocardial injury after major noncardiac surgery.

BACKGROUND: About 300 million surgeries are performed worldwide annually and this figure is increasing constantly. Peri-operative myocardial injury (PMI), detected by cardiac troponin (cTn) elevation, is a common cardiac complication of noncardiac surgery, strongly associated with short- and long-term mortality. Without systematic peri-operative cTn screening, most cases of PMI may go undetected. However, little is known about cost effectiveness of a systematic PMI screening strategy with high-sensitivity cardiac troponin T (hs-cTnT) after noncardiac surgery. OBJECTIVE: To assess, in patients with high cardiovascular risk, the cost-effectiveness of a systematic screening strategy using a hs-cTnT assay, to identify patients with PMI after major noncardiac surgery, compared with usual care. DESIGN: Cost-effectiveness analysis; single centre prospective cohort study. SETTING: Spanish University Hospital. PATIENTS: From July 2016 to March 2019, we included 1477 consecutive surgical patients aged ≥65 or if <65, with documented history of cardiovascular disease or impaired renal function, who underwent major noncardiac surgery and required at least an overnight hospital stay. We excluded patients aged <65 years without cardiovascular disease, undergoing minor surgery, or with an expected <24 h hospital stays. INTERVENTIONS: We conducted a decision-tree analysis, comparing a systematic screening strategy measuring hs-cTnT before surgery, and at the 2nd and 3rd days after surgery vs. a usual care strategy. We considered a third-party payer perspective and the outcomes of both strategies in the short-term (30 days follow-up). Information about costs was expressed in Euros-2021. We calculated the incremental cost-effectiveness ratio (ICER) of the systematic hs-cTnT strategy, defined as the expected cost per any additional PMI detected, and explored the robustness of the model using deterministic and probabilistic sensitivity analysis. MAIN OUTCOME MEASURES: ICER of the systematic hs-cTnT screening strategy. RESULTS: The ICER was €425 per any additionally detected PMI. The deterministic sensitivity analysis showed that a 15% variation in costs, and a 1% variation in the predictive values, had a minor impact over the ICER, except in case of the negative predictive value of the systematic hs-cTnT screening strategy. Monte Carlo simulations (probabilistic sensitivity analysis) showed that systematic hs-cTnT screening would be cost-effective in 100% of cases with a 'willingness to pay' of €780. CONCLUSIONS: Our results suggest that systematic peri-operative PMI screening with hs-cTnT may be cost-effective in the short-term in patients undergoing major noncardiac surgery. Economic evaluations, with a long-term horizon, are still needed. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03438448.

Continuous Glucose Monitoring Time-in-Range and HbA1c Targets in Pregnant Women with Type 1 Diabetes.

The CONCEPTT trial compared real-time Continuous Glucose Monitoring (RT-CGM) to capillary glucose monitoring in pregnant women with type 1 diabetes. We analyzed CGM and glycated hemoglobin (HbA1c) measures in first (n = 221), second (n = 197), and third (n = 172) trimesters, aiming to examine target glucose attainment and associations with pregnancy outcomes. CGM targets were Time-in-range (TIR) > 70%, Time-above-range (TAR) <25%, and Time-below-range (TBR) < 4%, and HbA1c targets < 6.5% (National Institute for Health and Care Excellence [NICE]) and HbA1c < 6.0% in second and third trimesters (American Diabetes Association [ADA]). TIR/TAR/TBR targets were achieved by 7.7/14.5/30.3% participants in first, 10.2/14.2/52.8% in second, and 35.5/37.2/52.9% in third trimesters. CGM target attainment was low but increased during pregnancy and with RT-CGM use. In the adjusted analyses, achieving TBR target was associated with a higher risk of pre-eclampsia and neonatal hypoglycemia. ADA HbA1c target attainment was low and unchanged during pregnancy (23.5/27.9/23.8%) but increased with RT-CGM use. In the adjusted analyses, HbA1c target attainment was associated with a lower risk of preterm birth, large-for-gestational age and neonatal hypoglycemia. We conclude that CONCEPTT trial participants had a low rate of CGM and of HbA1c target attainment. Attainment of CGM and NICE HbA1c targets increased throughout gestation and all targets (both NICE/ADA HbA1c and CGM) were more likely to be achieved by RT-CGM users, at 34 weeks' gestation. ADA HbA1c target achievement was independently associated with better perinatal outcomes, while the independent association of TBR target achievement with increased risk warrants further study. ClinicalTrials.gov Registration Identifier NCT01788527.

Impact of implementing a category 1 external quality assurance scheme for monitoring harmonization of clinical laboratories in Spain.

Background: The objective of the present study was to examine the evolution of the analytical performance specifications (APS) used in External Quality Assurance (EQA) schemes, as well as the efficacy of a category 1 EQA scheme in monitoring the harmonization of clinical laboratory results in Spain. Methods: A review of the literature on the types of quality specifications used in schemes in other countries and their evolution was performed. In addition, a comparative analysis of the potential impact that different APS from eight countries had on clinical decision-making was made based on three measurands: sodium, thyroid-stimulating hormone (TSH), and activated partial thromboplastin time (aPTT). Results: Harmonization of analytical methods was demonstrated by assessing whether average results deviated from the certified reference value of control materials within the APS derived from biological variation (BV). The APS used in EQA have evolved from state-of-the-art models to BV. Poor clinical decision-making would occur if the results accepted by some APS were applied. Conclusions: In Spain, only 2 of the 18 measurands studied are considered to be well harmonized. Closer collaboration between laboratories and analytical system providers would be required to resolve discrepancies.

Spanish society of laboratory medicine external quality assurance programmes: evolution of the analytical performance of clinical laboratories over 30 years and comparison with other programmes.

The purpose of this study is to understand the evolution of the analytical performance of the laboratories participating in the Spanish society of laboratory medicine (SEQCML) external quality assurance (EQA) programmes during its 30 years of operation and to compare it with the performance of other EQA programmes to establish whether the results are similar. The results obtained during this period are evaluated by applying the biological variability (BV) and state of the art-derived quality specifications. In addition, the results are compared with those obtained by other EQA programme organisations. It is noted that the laboratories participating in the EQA-SEQCML programmes have improved their performance over 30 years of experience and that the specifications derived from biological variation are achievable. It is difficult to compare EQA programmes, due to lack of accessibility and the differences in the design of these programmes (control materials, calculations used and analytical specifications established). The data from this study show that for some biological magnitudes the results obtained by the programmes are not yet harmonised, although efforts are being made to achieve this. Organisers of EQA programmes should also join the harmonisation effort by providing information on their results to enable comparison.

Valor diagnóstico del cociente de cadenas ligeras libres de inmunoglobulinas en suero en las gammapatías monoclonales de significado incierto / Diagnostic value of serum immunoglobulin free light chains ratio in monoclonal gammopathies of undetermined significance

Introducción. La medida de la concentración de las cadenas ligeras libres de inmunoglobulinas en suero proporciona información clínicamente relevante en el diagnóstico, pronóstico y monitorización de pacientes con mieloma múltiple (MM) y con gammapatías monoclonales de significado incierto (GMSI). En este trabajo se ha calculado el valor predictivo negativo (VPN) del cociente kappa/lambda libres (kappa/lambda) en un suero incluido dentro del rango diagnóstico (0,26-1,65), además de establecer unos nuevos valores discriminantes con un VPN del 100% en el grupo de pacientes estudiado. Material y métodos. La medida de la concentración de cadenas ligeras libres en suero se realizó por nefelometría en 157 muestras de pacientes diagnosticados de MM o GMSI y se calculó el cociente kappa/lambda libres. Resultados. El área bajo la curva de rendimiento diagnóstico para el cociente kappa/lambda libres fue de 0,885 en los pacientes con gammapatías con isotipo kappa y 0,879 en pacientes con gammapatías con isotipo lambda. El VPN para un cociente kappa/lambda libres entre 0,26 y 1,65 fue del 92%. Utilizando un intervalo de 0,36-1,0 se alcanzó un VPN del 100%. Conclusiones. La modificación del rango diagnóstico de 0,26-1,65 del cociente kappa/lambda libres por el comprendido entre 0,36 y 1,0, podría ser útil para obviar la realización de un aspirado de médula ósea en pacientes con criterios clínicos y analíticos de GMSI (AU)

Background. Measurement of immunoglobulin free light chains provides relevant clinical information for the diagnosis, prognosis and monitoring of multiple myeloma (MM) and monoclonal gammopathies of undetermined significance (MGUS). We evaluated the negative predictive value (NPV) of a serum free kappa to lambda (kappa/Lambda) ratio included within the described reference range (0.26-1.65) and also set cut-off points for the ratio in order to ensure a 100% NPV. Methods. Serum concentration of free light chains was measured by nephelometry in 157 individuals diagnosed as having MM or MGUS, and the free kappa/Lambda ratio was calculated. Results. The area under the curve of the free kappa/lambda ratio was 0.885 in the kappa type gammopathies subgroup, and 0.879 for the lambda subgroup. The NPV for a free kappa/lambda ratio between 0.26 and 1.65 was 92%. Using cut-off points of 0.36 and 1.0 for the ratio, achieved a 100% NPV. Conclusions. A change from the cut-off point 0.26-1.65 to 0.36-1.0 for the free kappa/lambda ratio could be useful in order to avoid performing a bone marrow aspirate in patients with MGUS clinical and laboratory criteria (AU)

High sensitivity troponin T concentrations in patients undergoing noncardiac surgery: a prospective cohort study.

OBJECTIVES: To determine the proportion of noncardiac surgery patients exceeding the published 99th percentile or change criteria with the high sensitivity Troponin T (hs-TnT) assay. DESIGN AND METHODS: We measured hs-TnT preoperatively and postoperatively on days 1, 2 and 3 in 325 adults. RESULTS: Postoperatively 45% (95% CI: 39-50%) of patients had hs-TnT≥14ng/L and 22% (95% CI:17-26%) had an elevation (≥14ng/L) and change (>85%) in hs-TnT. CONCLUSION: Further research is needed to inform the optimal hs-TnT threshold and change in this setting.

Cistatina C en la evaluación de la función renal / Assessment of renal function using cystatin C

La medición del filtrado glomerular es el mejor índice de valoración de la función renal. La creatinina sérica es el marcador de filtrado glomerular más utilizado, a pesar de estar sometido a diferentes fuentes de variabilidad. La cistatina C es una proteína de bajo peso molecular propuesta como marcador de función renal más sensible que la creatinina al detectar de forma precoz alteraciones en la función renal. La medida de cistatina C en suero en determinados grupos de pacientes como ancianos, niños o diabéticos parece aportar mayor información que la creatinina. Sin embargo, presenta alteraciones en su concentración sérica por factores diferentes al filtrado glomerular. Actualmente no hay evidencia científica suficiente que justifique el cambio de las ecuaciones de estimación del filtrado glomerular basadas en la concentración sérica de creatinina por la medida de la concentración sérica de cistatina C en la evaluación de la función (AU)

Glomerular filtration is the best index for assessing renal function. Despite being subjected to several sources of variability, serum creatinine is the most common glomerular filtration marker in use. Cystatin C is a low molecular weight protein which is more sensitive than creatinine, particularly for the identification of initial small decreases in renal function. The use of cystatin C in certain groups of patients such as elderly, children or diabetics appears to provide more information than creatinine. However, serum cystatin C can be influenced by non-renal factors. Currently, there is not enough scientific evidence to recommend the use of cystatin C to assess renal function instead of creatinine and creatinine equations (AU)

Comunicación de valores críticos: resultados de una encuesta realizada por la comision de la calidad extraanalítica de la SEQC / Critical values reporting: results of a Spanish laboratories survey

Introducción. La detección y comunicación de valores críticos es una de las funciones del laboratorio que más repercusión tiene sobre la seguridad del paciente. La Comisión de la Calidad Extraanalítica de la SECQ ha realizado unas encuestas para conocer la situación de los laboratorios españoles. Material y métodos. Se enviaron dos encuestas a 728 laboratorios participantes en el Programa de Garantía Externa de la Calidad de Bioquímica suero, para conocer diferentes aspectos relacionados con la comunicación de los mismos y el límite establecido para diferentes magnitudes, diferenciando entre consulta externa y hospitalización. Resultados. La mayoría de los laboratorios encuestados tienen definidos valores críticos (81,5 %) y es el facultativo del laboratorio quien los notifica (87,3 %) telefónicamente (91,1 %) al médico responsable del paciente (86,6 %). Un 58 % de laboratorios comprueba que el aviso se ha recibido, un 54,8 % no ha definido el plazo de entrega y el 87,9 % no utiliza un indicador para controlar este proceso. Resultados. Las medianas obtenidas para la mayoría de constituyentes no difieren según el origen de los pacientes, siendo parecidas para consulta externa y hospitalización. Sin embargo, se encuentran diferencias en el nivel bajo del calcio y en el nivel alto de la creatinina, la glucosa y la urea. Conclusiones. Se observa una falta de estandarización y consenso en el tratamiento de estos valores. Debido a que su detección implica una actuación médica urgente, consideramos necesario que los laboratorios en colaboración con los clínicos desarrollen estrategias adecuadas para el establecimiento y notificación de estos valores (AU)

Introduction. Detection and reporting of critical values have great implications on patient safety. The SEQC Committee for the extra-analytical quality assessment has carried out a survey in order to evaluate these in Spanish laboratories. Material and methods. Two surveys were distributed among 728 participants registered in the External Quality Assessment Scheme (clinical chemistry, serum). Participants were asked to provide information regarding reporting of critical values and their decision limits. Outpatient and in-patient reporting were considered separately. Results. Most laboratories (81.5 %) had their critical values already defined; physicians assumed the responsibility of notifying critical results in 87.3 % of cases; critical results were mainly informed by telephone (91.1 %); 58 % of laboratories further verified that such notifications were received; delivery time was not taken into account in 54.8 % of laboratories; 87.9 % did not employ any indicator to track this process. Results. Median values obtained for most constituents did not differ and were similar for outpatient and hospital settings. Nevertheless, differences were found for the lower calcium critical value and for high critical values for creatinine, glucose and urea. Conclusions. Handling of critical values lacks standardization and a consensus among Spanish laboratories. Suitable strategies should be developed between laboratories and clinicians in order to correctly define and set up critical values, as their detection requires urgent medical action (AU)

Respuesta inflamatoria de la exacerbación asmática de instauración rápida / Inflammatory Response of Rapid Onset Asthma Exacerbation

No se ha estudiado suficientemente la asociación entre la rapidez de instauración de la crisis de asma y la respuesta inflamatoria desencadenada.ObjetivoDeterminar los mecanismos inflamatorios que caracterizan la exacerbación asmática de instauración rápida.MétodoSe diseñó un estudio prospectivo y multicéntrico en los servicios de urgencias hospitalarias, que evaluó a 34 pacientes que se distribuyeron en tres grupos en función de las horas de instauración de la exacerbación asmática: (menos de 24h), instauración intermedia (25–144h), e instauración lenta (145 o más horas). Se recogieron datos clínicos, de esputo, sangre y orina en el momento de la primera atención y pasadas 24h, determinándose celularidad inflamatoria y marcadores solubles.ResultadosLos pacientes con exacerbación rápida presentaron una significativa mayor concentración de elastasa (1.028±1.140; 310±364; 401±390ng/ml) y albúmina (46,2± 4,3; 42±3,4; 39,9±4,8g/l) en sangre. El número de neutrófilos, eosinófilos, (tanto en sangre como en esputo), los niveles de proteína catiónica del eosinófilo (PCE) (sangre), interleuquina 8 (IL8) (sangre) y leucotrieno E4 (LTE4) (orina) estaban elevadas en los tres grupos (p>0,05). Se constataron asociaciones lineales entre el tiempo de instauración de la exacerbación y la intensidad de la obstrucción (FEV1) (r=−0,360; p=0,037), los eosinófilos en esputo (r=−0,399; p=0,029), la albúmina (r=−0,442; p=0,013); y con la IL8 (r=0,357; p=0,038).ConclusionesLos resultados sugieren una activación precoz de la respuesta neutrofílica y eosinofílica en la exacerbación asmática. No obstante, es posible que el edema bronquial juegue un papel importante en la respuesta inicial inflamatoria de las exacerbaciones dependiendo del tiempo de instauración(AU)

The association between onset of asthma exacerbation and the inflammatory response has not been sufficiently studied.ObjectiveTo determine the differential mechanisms of the rapid onset (RO) asthma exacerbation.MethodsWe designed a prospective, multicentre study that included 34 patients who suffered from asthma exacerbation. They were distributed into three groups of asthmatics, depending of the time of onset: from 0 to 24h, from 25 to 144h and more than 145h. We collected clinical data, sputum, blood and urine samples when first seen at the clinic and the next 24h later, and differential cell counts and biomarkers were determinedResultsThe asthmatics who suffered a RO exacerbation showed a higher elastase concentration, (1.028±1.140; 310±364; 401±390ng/ml) (P<0.05) and albumin (46.2±4.3; 42±3.4; 39.9±4.8g/l) (P<0.05) in the blood sample. Neutrophils, eosinophils (blood or sputum), eosinophil cationic protein (ECP) (blood), interleukin 8 (IL8) (blood) and leukotriene E4 (LTE4) (urine) were high in the three groups (P>0.05). We demonstrated an association between the onset of exacerbation and the severity of obstruction (FEV1) (r=−0.360; P=0.037), eosinophils in sputum (r=−0.399; P=0.029), albumin (r=−0.442; P=0.013), and IL8 in sputum (r=0.357; P=0.038).ConclusionsThe results suggest a rapid inflammatory response, both neutrophilic and eosinophilic, in the asthmatic exacerbation. However, the swelling in the bronchi may play an important role in the initial inflammatory response in the exacerbations depending of time of onset(AU)

[Inflammatory response of rapid onset asthma exacerbation]. / Respuesta inflamatoria de la exacerbación asmática de instauración rápida.

UNLABELLED: The association between onset of asthma exacerbation and the inflammatory response has not been sufficiently studied. OBJECTIVE: To determine the differential mechanisms of the rapid onset (RO) asthma exacerbation. METHODS: We designed a prospective, multicentre study that included 34 patients who suffered from asthma exacerbation. They were distributed into three groups of asthmatics, depending of the time of onset: from 0 to 24h, from 25 to 144h and more than 145h. We collected clinical data, sputum, blood and urine samples when first seen at the clinic and the next 24h later, and differential cell counts and biomarkers were determined RESULTS: The asthmatics who suffered a RO exacerbation showed a higher elastase concentration, (1.028±1.140; 310±364; 401±390ng/ml) (P<0.05) and albumin (46.2±4.3; 42±3.4; 39.9±4.8g/l) (P<0.05) in the blood sample. Neutrophils, eosinophils (blood or sputum), eosinophil cationic protein (ECP) (blood), interleukin 8 (IL(8)) (blood) and leukotriene E4 (LTE(4)) (urine) were high in the three groups (P>0.05). We demonstrated an association between the onset of exacerbation and the severity of obstruction (FEV(1)) (r=-0.360; P=0.037), eosinophils in sputum (r=-0.399; P=0.029), albumin (r=-0.442; P=0.013), and IL(8) in sputum (r=0.357; P=0.038). CONCLUSIONS: The results suggest a rapid inflammatory response, both neutrophilic and eosinophilic, in the asthmatic exacerbation. However, the swelling in the bronchi may play an important role in the initial inflammatory response in the exacerbations depending of time of onset.

Interferencias por contrastes yodados en la electroforesis capilar / Interference due to iodinated contrast media in capillary electrophoresis

Introducción. La administración de contrastes yodados puede interferir en la electroforesis capilar (EFC) de proteínas séricas. El objetivo fue realizar un estudio in vitro para confirmar la presencia de interferencias por Iomeron® en la EFC y otro in vivo en pacientes sometidos a coronariografías, estudiando la cinética de eliminación del contraste yodado. Material y métodos. Se preparó un pool de sueros libres de componente monoclonal (CM), con patrón electroforético anodino, añadiéndose Iomeron® hasta alcanzar una concentración de 5,4g/100ml. Partiendo de esta solución (A) se realizaron cuatro diluciones decrecientes (2,70g/100ml, 1,35g/100ml, 0,67g/100ml y 0,33g/100ml); y se procesaron por EFC para confirmar la interferencia y observar que disminuye proporcionalmente a su concentración. Material y métodos. Se extrajo sangre, pautadamente (5–10min, 1, 3, 5 y 8h postadministración del contraste) a pacientes sometidos a coronariografías. Se procesaron las muestras de plasma por EFC, y se realizó la inmunofijación (IF) de la obtenida entre los 5–10min para demostrar que la imagen electroforética no se correspondía con un CM. Resultados. La EFC reveló picos similares a los observados ante un CM en la fracción β, que desaparecieron en la dilución 0,33g/100ml en el estudio in vitro, y a las 8h postadministración del Iomeron® en el estudio in vivo (una paciente). Por otra parte, en la electroforesis de referencia del gel de agarosa empleado en la IF no se detectó imagen sugerente de CM. Conclusiones. Se demuestra que los picos observados correspondían a una interferencia producida por el Iomeron® en la fracción β de la EFC, no observada en la electroforesis en gel de agarosa (AU)

Introduction. The administration of iodinated contrast media may interfere with the capillary electrophoresis (CE) of serum proteins. The aim of the study was to perform an in vitro study to confirm the interference caused by lomeron® administration followed by an in vivo study in patients undergoing coronary angiographies, evaluating the kinetics of iodinated contrast elimination. Material and methods. A serum pool free from monoclonal component (MC) and with an anodyne electrophoretic pattern was prepared. lomeron® up to a concentration of 5.4g/100mL was added to this pool and afterwards, four decreasing dilutions were prepared (2.70g/100mL, 1.35g/100mL, 0.67g/100mL and 0.33g/100mL); all of them were processed by CE to confirm the interference and its decreasing effect as the concentration diminishes. Material and methods. Blood was drawn from patients undergoing coronary angiographies, at several time intervals (5–10min, 1, 3, 5 and 8h post-administration of contrast). Plasma samples were processed by CE, and immunofixation (IFx) of the first sample (5–10min) was performed in order to show that the electrophoretic image did not correspond to a MC. Results. In the in vitro study, CE revealed β fraction-MC peaks, which disappeared at the 0.33g/100mL dilution, and 8h after lomeron® administration in the in vivo study (one patient). On the other hand, no image suggestive of MC was detected on the reference agarose gel electrophoresis (AGE) used for the IFx. Conclusions. Peaks were observed that corresponded to an interference produced by lomeron® in the β fraction of CE, which was not found in AGE (AU)

Hemólisis en las muestras para diagnóstico / Hemolysis in diagnostic samples

La hemólisis es un efecto preanalítico evitable en la mayoría de los casos. Su aparición se debe a la técnica de extracción empleada y a las condiciones de transporte y preparación de las muestras. Su presencia produce error en muchas determinaciones habituales en química clínica, en muchos casos por la mezcla del contenido intraeritrocitario y en algún caso por el efecto interferente de componentes del hematíe, como la hemoglobina. En los laboratorios es necesario detectar y cuantificar la hemólisis en las muestras de forma estandarizada. La mayoría de los analizadores de bioquímica actuales incorporan sistemas de cuantificación espectrofotométrica de la hemoglobina. La influencia de la hemólisis en una magnitud depende de la metodología empleada, por lo que se debería solicitar a los fabricantes de equipos la realización de estudios y una información detallada sobre la influencia de la hemólisis en sus determinaciones, para que cada laboratorio pueda establecer el grado de hemólisis que supone error significativo para una magnitud, de acuerdo con sus especificaciones de calidad (AU)

In most cases, hemolysis is an avoidable preanalytical effect. It can appear as a result of the procedure used during blood specimen collection and also due to transport conditions and sample preparation. Hemolysis can lead to errors in many common determinations in clinical chemistry, mostly due to the leakage of cellular contents into the plasma, and in some cases, by the interfering effect of red blood cells components, such as hemoglobin. Laboratories need to be able to detect and measure hemolysis by a standardized procedure. The majority of current biochemistry analyzers can measure hemolysis by a spectrophotometric method. Nevertheless, the influence of hemolysis depends on the measurement method employed. Laboratories should demand that manufacturers give detailed information and make exhaustive studies regarding the influence of hemolysis on each analyte. This would allow each laboratory to establish the degree of hemolysis that produces a significant error in an analysis and in accordance with the laboratory's quality specifications (AU)

Nuevos marcadores en el síndrome coronario agudo / New biomarkers in acute coronary syndrome

La cardiopatía isquémica supone el 1,3% de los casos de atención en un servicio de urgencias hospitalario en España. El manejo del paciente es complejo por el riesgo de producir una alta médica incorrecta, el beneficio de instaurar una revascularización rápida y el gasto excesivo por admisiones injustificadas. La última década ha permitido un importante avance en el desarrollo de nuevos marcadores cardíacos. Tradicionalmente los marcadores del síndrome coronario agudo han sido indicadores de necrosis cardíaca. Esta función se ha ampliado actualmente. Aún hay muchas limitaciones en la medición de estos marcadores, como la falta de un procedimiento estandarizado o materiales de referencia certificados. Además de las troponinas cardíacas y el electrocardiograma, medir la albúmina modificada por isquemia puede ayudar a excluir un síndrome coronario agudo en pacientes con baja probabilidad de isquemia miocárdica. La proteína fijadora de ácidos grasos-H es un marcador de necrosis útil en el diagnóstico precoz del infarto agudo de miocardio. En el pronóstico del síndrome coronario agudo, la proteína C reactiva, los péptidos natriuréticos y la mieloperoxidasa complementan el valor pronóstico de la troponina. El ligando soluble CD40 permite la clasificación e individualización del tratamiento del síndrome coronario agudo. Actualmente no hay suficiente evidencia para que ningún nuevo marcador sustituya a los que recomiendan las sociedades científicas ni se dispone de procedimientos de medición rápidos para algunos de ellos. Deben establecerse paneles utilizando la evidencia científica disponible y tomando como objetivo su contribución a una mejor evolución del paciente(AU)

Myocardical ischemia involves 1.3% of the patients attending emergency departments in Spain. The management of these patients is complex, due to the risk of an incorrect discharge diagnosis, the benefit of rapid revascularization and the excessive cost due to unnecessary admissions. There has been a significant improvement in the development of new cardiac biomarkers over the last ten years. Biomarkers traditionally used for identifying acute coronary syndrome were indicators of myocardial necrosis. This role has currently been expanded. There are still some limitations in the measurement of these biomarkers, due to lack of standardised assays or certified calibrators. Ischemia-modified albumin in conjunction with cardiac troponin and electrocardiogram, can help to rule out an acute coronary syndrome in patients with a low probability of having myocardical ischemia. Heart-type fatty acid-binding protein is a strong necrosis biomarker in the early diagnosis of acute myocardical infarction. C-reactive protein, natriuretic peptides and myeloperoxidase have been shown to complement cardiac troponin in the prognosis of acute coronary syndrome. Soluble CD40 ligand enables the identification of a subgroup of patients who will benefit from a treatment in acute coronary syndrome. There is currently not enough evidence to replace new biomarkers with any of these already been recommended by the scientific societies. Also, the assays of some of them are not sufficiently rapid. A multimarker strategy must be created to take into account the existing scientific-based evidence, with the aim of improving outcomes in patients(AU)

Preanalytical quality control program - an overview of results (2001-2005 summary).

BACKGROUND: Preanalytical variables, such as sample collection, handling, transport, and storage, may affect patient results. The number of errors in the preanalytical phase may decrease by following standardized procedures. METHODS: A retrospective analysis (2001-2005) of results obtained through the Spanish Society of Clinical Chemistry and Molecular Pathology Quality Assessment Program for the Preanalytical Phase has been carried out to summarize data regarding the main factors affecting the preanalytical phase quality. In such a program, participants are asked to register rejections and causes for rejection of routine or stat samples usually and locally collected at their laboratories. RESULTS: Results discussed refer to 105 laboratories. Of the 4,715,132 tubes expected to be received during the data collection period among participating laboratories and according to determinations included by clinicians in the request form, 32,977 (0.699%) offered a cause for rejection. Whole blood-EDTA samples and serum samples accounted for 75.6% of all samples collected among laboratories, although they only corresponded to 55.8% of all registered rejections. In total, 81% of rejections arose as a result of the following reasons: "specimen not received" (37.5%), "hemolysis" (29.3%), and "clotted sample" (14.4%). Moreover, plasma-citrate-erythrocyte sedimentation rate exhibited the highest percentage of rejection (1.473%), whereas the lowest rate corresponded to whole blood-EDTA (0.381%). CONCLUSIONS: Overall percentage of rejection is similar to previously published data. As some of the included variables have turned out to be irrelevant, the program has been simplified from the year 2006 onwards.

[Swelling of the bronchial mucose and quickness of onset in acute asthma]. / Edema de la mucosa bronquial y rapidez de instauración de la crisis de asma.

BACKGROUND AND OBJECTIVE: The plasma protein leakage produced in the bronchial mucose of patients with acute asthma might be associated to the quickness of the onset exacerbation. The aim of this study was to study this association. PATIENTS AND METHOD: 22 patients with acute asthma were recruited, and the magnitude of plasma protein leakage was measured by the concentrations of albumin and alpha2-macroglobulin in sputum. RESULTS: Days of onset in acute asthma correlated negatively with albumin sputum concentration (r = -0.563; p = 0.006), alpha2-macroglobulin sputum concentration (r = -0.603; p = 0.003), and related relative coefficients of albumin sputum/serum (r = -0.538; p = 0.01) and alpha2-macroglobulin sputum/serum (r = -0.514; p = 0.014). When the sample was divided by the following daily cutoff: < or = 4, patients suffering from a shorter onset of acute asthma showed a higher concentration of alpha2-macroglobulin in sputum: mean (standard deviation) of 14.4 (18) versus 5.3 (5.4) (p = 0.028). CONCLUSIONS: Plasma protein leakage seems to play an important role in the inflammatory pathogenesis of asthma exacerbation. The quicker onset of asthma the more plasma protein extravasation to the bronchial lumen.

Edema de la mucosa bronquial y rapidez de instauración de la crisis de asma / Swelling of the bronchial mucose and quickness of onset in acute asthma

Fundamento y objetivo: El edema de la mucosa bronquial que se produce en la crisis de asma podría estar relacionado con la rapidez de la instauración. El objetivo del presente estudio ha sido determinar dicha relación. Pacientes y método: Se incluyó en el estudio a 22 pacientes con exacerbación asmática, en quienes se estimó la magnitud del edema bronquial mediante la constatación de la extravasación proteica de la concentración de albúmina y de macroglobulina *2 en esputo. Resultados: Se observó una relación significativa entre un menor número de días de instauración de la crisis y una mayor concentración de albúmina en esputo (r = ­0,563; p = 0,006); mayor cantidad de macroglobulina *2 en esputo (r = ­0,603; p = 0,003); mayor índice relativo de la concentración de albúmina esputo/suero (r = ­0,538; p = 0,01) e índice relativo de la concentración de macroglobulina *2 esputo/suero (r = ­0,514; p = 0,014). Cuando la muestra se dividió según el número de días de evolución en la instauración de la crisis fuera mayor o menor de 4, el grupo con menos días presentó mayor extravasación de macroglobulina *2, con una media (desviación estándar) de 14,4 (18) frente a 5,3 (5,4) (p = 0,028). Conclusiones: El edema bronquial parece desempeñar un papel relevante en la patogenia inflamatoria de la exacerbación asmática. Las crisis de asma instauradas más rápidamente presentan mayor edema de la mucosa bronquial

Background and objective: The plasma protein leackage produced in the bronchial mucose of patients with acute asthma might be associated to the quickness of the onset exacerbation. The aim of this study was to study this association. Patients and method: 22 patients with acute asthma were recruited, and the magnitude of plasma protein leackage was meassured by the concentrations of albumin and *2-macroglobulin in sputum. Results: Days of onset in acute asthma correlated negatively with albumin sputum concentration (r = ­0.563; p = 0.006), *2-macroglobulin sputum concentration (r = ­0.603; p = 0.003), and related relative coefficients of albumin sputum/serum (r = ­0.538; p = 0.01) and *2-macroglobulin sputum/serum (r = ­0.514; p = 0.014). When the sample was divided by the following daily cutoff: ¾ 4, patients suffering from a shorter onset of acute asthma showed a higher concentration of *2-macroglobulin in sputum: mean (standard deviation) of 14.4 (18) versus 5.3 (5.4) (p = 0.028). Conclusions: Plasma protein leackage seems to play an important role in the inflammatory pa-thogenesis of asthma exacerbation. The quicker onset of asthma the more plasma protein extravasation to the bronchial lumen

Cystatin C as a marker of GFR--history, indications, and future research.

OBJECTIVE: To summarize recent knowledge on the small molecular weight protein cystatin C (cys-C) and its use as a marker of the glomerular filtration rate (GFR). METHODS: A multinational expert meeting was held in April 2002 in Marburg, Germany. Contributors summarized their main findings. CONCLUSIONS: Cys-C is at least equal if not superior to serum creatinine as a marker of GFR. The independence from height, gender, age, and muscle mass is advantageous. Select patient groups such as children, the elderly, and patients with reduced muscle mass benefit in particular.