sFlt-1/PlGF for prediction of early-onset pre-eclampsia: STEPS (Study of Early Pre-eclampsia in Spain).

OBJECTIVE: A high ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) has been linked to pre-eclampsia (PE). We evaluated the sFlt-1/PlGF ratio as a predictive marker for early-onset PE in women at risk of PE. METHODS: This prospective, Spanish, multicenter study included pregnant women with a risk factor for PE, including intrauterine growth restriction, PE, eclampsia or hemolysis, elevated liver enzymes and low platelet count syndrome in previous pregnancy, pregestational diabetes or abnormal uterine artery Doppler. The primary objective was to show that the sFlt-1/PlGF ratio at 20, 24 and 28 weeks' gestation was predictive of early-onset PE (< 34 + 0 weeks). Serum sFlt-1 and PlGF were measured at 20, 24 and 28 weeks. Multivariate logistic regression was used to develop a predictive model. RESULTS: A total of 819 women were enrolled, of which 729 were suitable for analysis. Of these, 78 (10.7%) women developed PE (24 early onset and 54 late onset). Median sFlt-1/PlGF ratio at 20, 24 and 28 weeks was 6.3 (interquartile range (IQR), 4.1-9.3), 4.0 (IQR, 2.6-6.3) and 3.3 (IQR, 2.0-5.9), respectively, for women who did not develop PE (controls); 14.5 (IQR, 5.5-43.7), 18.4 (IQR, 8.2-57.9) and 51.9 (IQR, 11.5-145.6) for women with early-onset PE; and 6.7 (IQR, 4.6-9.9), 4.7 (IQR, 2.8-7.2) and 6.0 (IQR, 3.8-10.5) for women with late-onset PE. Compared with early-onset PE, the sFlt-1/PlGF ratio was significantly lower in controls (P < 0.001 at each timepoint) and in women with chronic hypertension (P < 0.001 at each timepoint), gestational hypertension (P < 0.001 at each timepoint) and late-onset PE (P < 0.001 at each timepoint). A prediction model for early-onset PE was developed, which included the sFlt-1/PlGF ratio plus mean arterial pressure, being parous and previous PE, with areas under the receiver-operating characteristics curves of 0.86 (95% CI, 0.77-0.95), 0.91 (95% CI, 0.85-0.97) and 0.93 (95% CI, 0.86-0.99) at 20, 24 and 28 weeks, respectively, and was superior to models using the sFlt-1/PlGF ratio alone or uterine artery mean pulsatility index. CONCLUSIONS: The sFlt-1/PlGF ratio can improve prediction of early-onset PE for women at risk of this condition. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

[Anti-apoptotic potencial role of p38 in prostate cancer]. / Potencial anti-apoptótico de p38 en cáncer de próstata.

INTRODUCTION: TNF-alpha transduction pathway in prostate cancer seems to be diverted towards p38 activation. P38 may protect prostate tumoral cells from TNF-alpha apoptosis induced. The aim of this study was study the role of p38 in vivo (were evaluated some p38 downstream factors), as well as in vitro (in prostatic tumoral cell lines, LNCaP and PC3, pre-treated with TNF-alpha). MATERIAL AND METHODS: Two prostatic tumoral cell lines (LNCaP and PC3) were used in in vitro studies. Two different experiments were made: with TNF-alpha (several concentrations) and p38 specific inhibitor (SB203580). The apoptotic index were evaluated using DAPI staining and flow cytometry. P38 activation was measured by Western blot analysis. 15 normal samples (NP) and 27 prostate cancer samples (PC) were used in in vivo study, all of them were processed for immunohistochemistry and Western-blot. RESULTS: In vitro, TNF-alpha induced apoptosis in LnCap when we increased its concentration but not in PC3. TNF-alpha stimulation led to increase a time-dependent p38 phosphorylation in two intermediate doses whereas in PC3 not changes were found. In LNCaP after its preincubation with SB203580 and TNF-alpha treatment showed a significative increasing of apoptosis. In vivo, all NP samples were found positives to p-Elk-1 and p-ATF-2 (nuclei of epithelial cells). In PC the expression of p-Elk-1 or p-ATF-2 increased and was located in the nucleus and cytoplasm of epithelial cells. CONCLUSION: Our data in vitro and in vivo suggest that p38 plays a very important role in prostatic tumour progression. These data suggest that the control activation of p38 might be a possible target to cancer prostate treatment.

Hypercoagulable state after thrombolytic therapy in patients with acute myocardial infarction (AMI) treated with streptokinase.

Fibrinogen activity was studied in 70 patients with AMI who were treated with an intravenous infusion of SK (800,000 U/30 min or 1.5 mill U/60 min). Patients received a continuous infusion of heparin after thrombolytic therapy was completed. 800,000 U and 1.5 mill U SK recanalized infarct-related arteries at a rate of 78%. Early re-infarction occurred in 6% in each group. Upon admission to the hospital patients showed a hypercoagulable state that may be related to an elevated level of fibrinogen and HMW fibrinogen (70.5 +/- 2 vs 65 +/- 2% in patient and normal plasmas, respectively) that changed to a transitory hypercoagulable state indicated by decreased fibrinogen levels after SK treatment. Forty-eight hours after SK, a new fibrinogen hyperfunction, related to an increase in fibrinogen level and especially HMW synthesized fibrinogen (82 +/- 1 or 81 +/- 1%, 800,000 and 1.5 mill U SK, respectively) was observed, which was neutralized by heparin therapy (1,660 U/h with continuous infusion). The elevated levels of fibrinogen (363 +/- 21 vs 240 +/- 8 mg/dl in patient and normal plasmas, respectively) and HMW fibrinogen (70 +/- 3% with both SK hypercoagulable state that is not neutralized by the heparin dose were compared with those whose arteries recanalized. The former group had a higher concentration of fibrinogen (197 +/- 31 vs 147 +/- 18 mg/dl), HMW fibrinogen (78 +/- 0.5 vs 74 +/- 0.3%, respectively), and FPA (130 +/- 3 vs 6 +/- 4 pmol/ml) and more extensive fibrin gel formation kinetics (gelation rate 3.3 +/- 1.4 vs 1.1 +/- 0.2 OD/s x 10(-4), respectively) than the second group. The hypercoagulable state found in patients with acute myocardial infarction undergoing thrombolytic therapy may be related mainly to the progression of HMW fibrinogen and fibrinogen levels.

Human fibrinogen heterogeneity. A study of limited fibrinogen degradation.

Different fibrinogen species were examined in normal plasma following urokinase treatment, in isolated high molecular weight fibrinogen treated with plasmin and in plasma samples from patients with acute myocardial infarction receiving thrombolytic therapy. In normal plasmas two main fibrinogen species (Mr = 340,000 and Mr = 320,000) and an intermediate fragment (Mr = 330,000) were observed. The 340,000 fibrinogen was the most sensitive to degradation; it gave rise to 330,000 and 320,000 species. Degradation of isolated 340,000 fibrinogen was similar to plasma fibrinogen degradation. After thrombolytic therapy in acute myocardial infarction patients, when the plasma fibrinogen decreased near to zero, the new synthesized fibrinogen was 340,000 form. 'In vivo' conversion of 340,000 to 320,000 fibrinogen, associated with the transitory 330,000 form, was observed. The coagulation study of plasma fibrinogen showed that when Mr 340,000 fibrinogen decreased (40%), the gelation rate decreased and lag time increased drastically. The high 340,000 fibrinogen content found in acute myocardial infarction patients gave rise to the hypercoagulable state.

Hyperhomocysteinemia, obesity and cryptogenic stroke.

BACKGROUND: The pathogenic role of hyperhomocysteinemia in cryptogenic stroke is not well established. We aimed to determine homocysteine levels in patients with cryptogenic stroke considering the possible variables that may act as confounders and analyze the influence of obesity on this association. PATIENTS AND METHODS: We conducted a case-control study in 123 patients with cryptogenic stroke aged 42 ± 12 years and in 153 control subjects aged 42 ± 13 years. Serum homocysteine was determined by fluorescence polarization immunoassay. RESULTS: Patients showed statistically higher levels of homocysteine, creatinine and higher BMI than controls (p = 0.045, p = 0.014, p = 0.013), respectively. After multivariate adjustment the differences in homocysteine levels disappeared (p = 0.774). When subjects were classified according to the presence or absence of obesity, the differences in the prevalence of hyperhomocysteinemia (homocysteine >15 µM) were highly significant, being higher in patients than in controls (p = 0.009). Likewise, mean values of homocysteine in obese were higher in cases than in controls (16.9 ± 9.5 µM vs. 10.12 ± 2.5 µM; p = 0.020), remaining significant after adjusting for the above mentioned confounders. CONCLUSION: Although in general, hyperhomocysteinemia does not seem to constitute an independent risk factor for cryptogenic stroke, it significantly increases the risk in obese subjects; therefore it is convenient to decrease its levels in this sub-group to minimize the risk.

[Quality assessment for preanalytical phase in clinical laboratory: a multicentric study]. / Evaluación de la calidad en el laboratorio en la fase preanalítica: un estudio multicéntrico.

PURPOSE: To show the number of preanalytical sample errors in seven laboratories attending seven health departments of Valencian Community (Spain). METHODS: Cross-sectional study of the number of preanlytical errors in samples obtained in primary care centers. An error is defined as a rejected specimen: any blood or urine sample, which cannot be successfully tested as it does not meet the acceptability criteria of the laboratory or if the sample is not received. We collected preanalytical errors from the tests requested for hematology, coagulation, chemistry, and urine samples. Registers were collected and indicators calculated automatically through a data warehouse and OLAP cubes software. RESULTS: Large differences in the results of preanalytical errors were observed between health departments. The highest percentage of errors occurred in coagulation samples, followed by urine, hematology and biochemistry. With regard to the type of error, the largest proportion of errors was due to failures of process. CONCLUSIONS: The high incidence of preanalytical errors and variability between health departments suggests that there is a need to standardize the drawing practice.

[Regional pilot study to evaluate the laboratory turnaround time according to the client source]. / Estudio piloto regional de evaluación del tiempo de respuesta de laboratorio según el tipo de cliente.

PURPOSE: To show turnaround time to client source in eight laboratories covering eight Health Areas (2,014,475 inhabitants) of the Valencian Community (Spain). MATERIAL AND METHODS: Internal Laboratory Information System (LIS) registers (test register and verification date and time), and daily LIS registers were used to design the indicators, These indicators showed the percentage of key tests requested (full blood count and serum glucose and thyrotropin) that were validated on the same day the blood was taken (inpatients and Primary Care and/or at 12 a.m. (inpatients). Urgent (stat) tests were also registered as key tests (serum troponin and potassium) and were recorded in minutes. Registers were collected and indicators calculated automatically through a Data Warehouse application and OLAP cube software. RESULTS: Long turnaround time differences were observed at 12 a.m. in inpatients, and in the day of sample extraction in primary care patients. The variability in turnaround of stat tests is related to hospital size, activity and validation by the laboratory physician. CONCLUSIONS: The study results show the large turnaround time disparity in eight Health Care Areas of Valencian Community. The various requesting sources covered by the laboratories create the need for continuous mapping processes redesign and benchmarking studies to achieve customer satisfaction.

Decreased high-molecular weight fibrinogen and impaired alpha-chain polymerization in full-term newborns.

Some properties of fibrinogen from 30 newborn and 30 normal adult plasmas obtained under the same conditions have been studied. The results show that the high-molecular weight fibrinogen (HMW-Fg) was decreased by nearly 25% in newborn plasma as compared to normal adult values. The kinetics of fibrin gel formation was decreased in newborn as compared with normal adult plasmas (gelation rates 2.2 +/- 1 vs. 5.6 +/- 0.5 x 10(-4) OD/s, lag time 128 +/- 25 vs. 72 +/- 3 s). The release rates of fibrinopeptide A (FPAp +/- FPA) and fibrinopeptide B (FPB) were decreased in newborn fibrinogen (FPAp + FPA 10.8 and FPB 1.2 x 10(-3) s-1) as compared to normal adult fibrinogen (FPAp + FPA 11.8 and FPB 1.7 x 10(-3) s-1). Analysis by SDS-PAGE of the reduced, highly cross-linked fibrin from the newborns showed that only 23% of the alpha-chain participates in the formation of alpha-chain polymers. The results suggest that the retarded release rate of fibrinopeptides and the decrease in the HMW fibrinogen concentration are causes of the prolonged kinetics of fibrin gel formation in newborns.

Evaluación de la calidad en el laboratorio en la fase preanalítica: un estudio multicéntrico / Quality assessment for preanalytical phase in clinical laboratory: a multicentric study

Introducción. El objetivo del trabajo es mostrar y analizar los resultados de errores preanalíticos en las muestras de laboratorio remitidas desde atención primaria a 7 laboratorios de la Comunidad Valenciana que atienden a 7 departamentos de salud. Material y métodos. Se realizó un estudio transversal mediante la evaluación y el análisis de los errores preanalíticos de 7 laboratorios. El error preanalítico se definió como muestra que no puede ser analizada por no cumplir los criterios de aceptabilidad o que no se recibe en el laboratorio. Se diseñaron indicadores de proporción que cuantifican cada incidencia respecto al total de cada muestra (hematología, coagulación, bioquímica y orina). Los errores preanalíticos y las muestras se recogieron automáticamente del Sistema de Información del Laboratorio, y también se calcularon los indicadores a tiempo real mediante un software basado en data warehouse y cubos OLAP. Resultados. La variabilidad de los resultados entre los diferentes centros fue elevada, evidenciándose que el mayor porcentaje de incidencias se debió a la falta de disponibilidad de las muestras, en especial de coagulación y de orina. Conclusiones. Existe una gran variabilidad de errores preanalíticos dependiendo del Departamento de Salud. Existe una necesidad de homogeneizar la práctica de la extracción de muestras(AU)

Purpose. To show the number of preanalytical sample errors in seven laboratories attending seven health departments of Valencian Community (Spain). Methods. Cross-sectional study of the number of preanlytical errors in samples obtained in primary care centers. An error is defined as a rejected specimen: any blood or urine sample, which cannot be successfully tested as it does not meet the acceptability criteria of the laboratory or if the sample is not received. We collected preanalytical errors from the tests requested for hematology, coagulation, chemistry, and urine samples. Registers were collected and indicators calculated automatically through a data warehouse and OLAP cubes software. Results. Larges differences in the results of preanalytical errors were observed between health departments. The highest percentage of errors occurred in coagulation samples, followed by urine, hematology and biochemistry. With regard to the type of error, the largest proportion of errors was due to failures of process. Conclusions. The high incidence of preanalytical errors and variability between health departments suggests that there is a need to standardize the drawing practice(AU)

Estudio piloto regional en la Comunidad Valenciana. Indicadores financieros del laboratorio clínico / No disponible

El objetivo del trabajo es proponer un sistema de indicadores de gestión a partir de los datos normalizados del Sistema de Información conómico ( SIE) de la Agencia Valenciana de Salud que aplica a los laboratorios públicos de la Comunidad Valenciana. Como resultados se obtienen indicadores de costes, de complejidad, de rendimiento de personal y de rendimiento de material y se establece una comparación con los datos del SIE 2008 de los 9 laboratorios participantes. En conclusión, la obtención de los indicadores de gestión a partir del Sistema de Información Económico, no supone ningún trabajo adicional para el laboratorio; la información es homogénea y la comparación interlaboratorios proporciona una información de gran utilidad para la gestión de los laboratorios (AU)

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Estudio piloto regional de evaluación del tiempo de respuesta de laboratorio según el tipo de cliente / Regional pilot study to evaluate the laboratory turnaround time according to the client source

Objetivo. Presentar los resultados del tiempo de respuesta relacionado con el tipo de cliente en ocho laboratorios clínicos de la Comunidad Valenciana que atienden a ocho departamentos de salud (2.014.475 habitantes). Material y métodos. Se utilizaron registros internos (fecha/hora de registro y validación de la prueba) y registros diarios (tipo de paciente) del Sistema Informático del Laboratorio para construir los indicadores. Estos indicadores muestran el porcentaje de pruebas clave (hemograma y glucosa y tirotropina séricas) solicitadas que son validadas en el mismo día de la extracción de muestra (pacientes ingresados o de atención primaria) y/o antes de las 12.00 a.m. (pacientes ingresados). El tiempo de respuesta de pruebas urgentes se refirió a pruebas clave (troponina y potasio séricos) y se expresó en minutos. La recogida de registros y el cálculo de indicadores se realizó de forma automática mediante una aplicación informática basada en data warehouse y cubos OLAP. Resultados. Se observaron grandes diferencias en los porcentajes de validación antes de las 12.00 a.m. para pacientes ingresados y en el día de la extracción para pacientes de atención primaria. La variabilidad observada en los tiempos de respuesta de pruebas urgentes se relacionó con el tamaño del hospital, actividad y validación por el facultativo del laboratorio. Conclusiones. El estudio de benchmarking ha servido para mostrar la gran disparidad de tiempos de respuesta en ocho departamentos de salud de la Comunidad Valenciana. La atención en el laboratorio a distintos tipos de clientes crea la necesidad de la continua adaptación de los procesos para conseguir su satisfacción(AU)

Purpose. To show turnaround time to client source in eight laboratories covering eight Health Areas (2,014,475 inhabitants) of the Valencian Community (Spain). Material and methods. Internal Laboratory Information System (LIS) registers (test register and verification date and time), and daily LIS registers were used to design the indicators, These indicators showed the percentage of key tests requested (full blood count and serum glucose and thyrotropin) that were validated on the same day the blood was taken (inpatients and Primary Care and/or at 12 a.m. (inpatients). Urgent (stat) tests were also registered as key tests (serum troponin and potassium) and were recorded in minutes. Registers were collected and indicators calculated automatically through a Data Warehouse application and OLAP cube software. Results. Long turnaround time differences were observed at 12 a.m. in inpatients, and in the day of sample extraction in primary care patients. The variability in turnaround of stat tests is related to hospital size, activity and validation by the laboratory physician. Conclusions. The study results show the large turnaround time disparity in eight Health Care Areas of Valencian Community. The various requesting sources covered by the laboratories create the need for continuous mapping processes redesign and benchmarking studies to achieve customer satisfaction(AU)

Potencial anti-apoptótico de p38 en cáncer de próstata / Anti-apoptotic potencial role of P38 in prostate cancer

Introducción: En cáncer de próstata, la vía de señalización intracelular de TNF-α parece estar desviada hacia la activación de p38. p38 podría proteger a las células tumorales de la muerte inducida por TNF-α. Nos propusimos estudiar el papel que desempeña p38 tanto in vivo (evaluando algunos factores activados por p38 en cáncer de próstata), como in vitro (en las líneas celulares tumorales de próstata LNCaP y PC3, tratadas previamente con TNF-α).Material y métodos: Para los estudios in vitro se utilizaron las líneas celulares LNCaP y PC3. Los tratamientos se realizaron con TNF-α (diferentes concentraciones) y el inhibidor específico de p38 (SB203580). El índice apoptótico se evaluó mediante DAPI y citometría de flujo. La activación de p38 se determinó mediante Western blot. Para los estudios in vivo se usaron 15 próstatas normales (PN) y 27 de cáncer (CP) procesadas para inmunohistoquímica y Western blot. Resultados: In vitro, el aumento de la concentración de TNF-α indujo apoptosis en LNCaP, pero no en PC3. El tratamiento con TNF-α produjo un aumento de la fosforilación de p38 en concentraciones intermedias, mientras que enPC3 no se observaron cambios en la activación. El pretratamiento con SB203580 y TNF-α produjo un aumento significativo de la apoptosis en LNCaP. In vivo todos los pacientes con PN resultaron positivos para p-Elk-1 y p-ATF-2 (núcleo de células epiteliales). En CP no sólo aumenta la expresión de estos factores, sino que se localizaron tanto en núcleo como en citoplasma. Conclusión: Nuestros datos in vitro e in vivo sugieren que p38 juega un importante papel en la progresión del cáncerde próstata. Estas observaciones sugieren que tratamientos centrados en el control de la activación de p38 podrían serefectivos en el tratamiento contra el cáncer de próstata (AU)

Introduction: TNF-α transduction pathway in prostate cancer seems to be diverted towards p38 activation. P38 may protect prostate tumoral cells from TNF-α apoptosis induced. The aim of this study was study the role of p38 in vivo (were evaluated some p38 downstream factors), as well as in vitro (in prostatic tumoral cell lines, LNCaP and PC3, pre-treated with TNF-α).Material and methods: Two prostatic tumoral cell lines (LNCaP and PC3) were used in in vitro studies. Two different experiments were made: with TNF-α (several concentrations) and p38 specific inhibitor (SB203580). The apoptotic index were evaluated using DAPI staining and flow cytometry. P38 activation was measured by Western blot analysis. 15 normal samples (NP) and 27 prostate cancer samples (PC) were used in vivo study, all of them were processed for immunohistochemistry and Western-blot. Results: In vitro, TNF-α induced apoptosis in LnCap when we increased its concentration but not in PC3. TNF-α stimulationled to increase a time-dependent p38 phosphorylation in two intermediate doses where as in PC3 not changes were found. In LNCaP after its preincubation with SB203580 and TNF-α treatment showed a significative increasing of apoptosis. In vivo, all NP samples were found positives to p-Elk-1 and p-ATF-2 (nuclei of epithelial cells). In PC the expression of p-Elk-1 or p-ATF-2 increased and was located in the nucleus and cytoplasm of epithelial cells. Conclusion: Our data in vitro and in vivo suggest that p38 plays a very important role in prostatic tumour progression. These data suggest that the control activation of p38 might be a possible target to cancer prostate treatment (AU)

Perfiles enzimáticos detectados en enteropatógenos bacterianos mediante el sistema API ZYM / Enzymatic profiles detected in bacterial enteropathogens by APIZYM system

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