Longitudinal changes of angiogenic factors as a potential predictive tool in women with suspected preeclampsia.

OBJECTIVES: To investigate whether longitudinal changes of angiogenic factors (AF) sFlt-1, PlGF, and the sFlt-1/PlGF ratio, measured following identification of symptoms of preeclampsia (PE), could provide complementary information to the isolated measurements used in current clinical practice. STUDY DESIGN: Retrospective observational study. Sixty women with suspected PE and two AF results measured before gestational week (GW) 34 were included. Daily variation (DV) of AF was calculated from delta values and days elapsed between measurements. Through ROC analysis, the predictive performance of DV for PE-related events was estimated. Kaplan-Meier survival curves resulting from applying cutoff values were assessed. RESULTS: The sFlt-1, PlGF, and sFlt-1/PlGF ratio baseline levels showed significant differences between women without PE and women who developed early-onset PE (P < 0.001). DV of sFlt-1 and sFlt-1/PlGF ratio increased according to the severity of PE, showing significant differences in both pairs of groups compared (p < 0.001), so they were selected as potential predictors. Higher AUC values resulting from ROC analysis were 0.78 for early-onset PE, 0.88 for early-onset severe PE, 0.79 for occurrence of adverse maternal outcomes, and 0.89 for delivery before 37 GW, with sensitivity and specificity values higher than 0.71 and 0.80, respectively. The Kaplan-Meier analysis yielded significantly different curves (log-rank < 0.05), with shorter time-to-delivery as DV increased. CONCLUSION: Our results support the existence of a correlation between a progressive PlGF and sFlt-1 imbalance and a more aggressive clinical course of PE, detectable from the finding of PE symptoms. Its monitoring could be a useful predictive tool in women with suspected PE.

Measuring of Alpha-1 Antitrypsin Concentration by Nephelometry or Turbidimetry.

Most clinical laboratories quantify alpha-1 antitrypsin using either nephelometry or turbidimetry techniques because they are commercially available, amenable to automation, and precise. Both methods are based on light scatter. The foundation of both techniques is based on incubation of the specimen with anti-AAT polyclonal antibody solution, a polymer matrix between endogenous AAT and the reagent antibodies forms, leading to production of light-scattering large particles. Although these two terms are sometimes used synonymously, technically speaking they are not.Nephelometry measures the amount of turbidity or cloudiness of a solution by directly quantifying the intensity of the light scattered by insoluble particles in the sample. Therefore, this technique measures the light that passes through the sample, with the detector being placed at an angle from the sample. Turbidimetry is the process of measuring the loss of intensity of the light transmitted linearly through a sample caused by the scattering effect of insoluble particles. The decrease in light transmission is measured compared to a reference, and the absorbed light is quantified.Beyond specific technical differences between both techniques, there are two major differences between the two procedures that may influence the results. First, the concentration of the sample and the resulting intensity of scattered light relative to the intensity of the light source is one major factor. Second, the size of the scattering particles is also a key differentiating factor. This chapter describes the technical requirements, the different protocols, and the clinical applicability of these two techniques in the diagnosis of alpha-1 antitrypsin deficiency.

Long-term follow-up with a clinical decision support system based on laboratory reports to manage patients with biochemical recurrence after radical prostatectomy.

INTRODUCTION: Currently, prostate cancer (PCa) is the second most common cause of cancer death, and radical prostatectomy (RP) remains the primary treatment for localized PCa. Although there is no consensus on an optimal strategy, the determination of total serum prostate-specific antigen (tPSA) is the cornerstone for the detection of postoperative biochemical recurrence (BCR). The aim of this study was to evaluate the prognostic utility of serial tPSA levels together with other clinicopathological factors and to assess the impact of a commentary algorithm implemented in our laboratory information system. METHODS: A descriptive and retrospective study of patients with clinically localized PCa who underwent RP. BCR-free survival was calculated over time (Kaplan-Meier analysis), and the ability of different clinicopathological factors to predict BCR was studied (univariate and multivariate analyses) with Cox models. RESULTS: A total of 203 patients underwent RP, of whom 51 presented with BCR during follow-up. In the multivariate model, doubling of tPSA, the Gleason score, tumour stage and tPSA nadir were detected as independent predictors of BCR. CONCLUSION: A patient with undetectable tPSA after 1959 days of RP is unlikely to develop BCR, regardless of preoperative or pathologic risk factors. Furthermore, doubling of tPSA in the first 2 years of follow-up was the main prognostic factor for BCR in patients undergoing RP. Other prognostic factors included a tPSA nadir detectable after surgery, a Gleason score ≥ 7 and a tumour stage T ≥ 2c.

Primary hypolactasia diagnosis: Comparison between the gaxilose test, shortened lactose tolerance test, and clinical parameters corresponding to the C/T-13910 polymorphism.

BACKGROUND & AIMS: There is no consensus on the most accurate method to diagnose primary hypolactasia. We aimed to compare the diagnostic accuracy of the new gaxilose test with 2 traditional tests (lactose tolerance test and clinical criteria) for the diagnosis of primary hypolactasia using the C/T-13910 polymorphism as a reference standard. METHODS: Patients with a clinical suspicion of lactose intolerance were subjected to gaxilose tests, shortened lactose tolerance tests, and symptom questionnaires before and after overload with 50 g lactose and after a lactose-free diet. The diagnostic accuracy and degree of agreement and correlation were assessed using a genetic test (C/T-13910 polymorphism) as a reference standard and their respective 95% confidence intervals. RESULTS: Thirty consecutive patients (70% women) participated in the study. The genetic test confirmed the C/T-13910 polymorphism in 11 patients (36.8%). The presence of diarrhoea and the symptom score after lactose overload, along with the tolerance test, were the variables with the highest degree of agreement (κ > 0.60). Area under the ROC curve was >0.82 (p < 0.05), with sensitivity and specificity values of >0.80. However, the gaxilose test obtained lower values: κ, 0.47; area under curve, 0.75 (0.57-0.94); sensitivity, 0.82 (0.55-1); and specificity, 0.68 (0.45-0.92). The multivariate analysis showed an association between the post-overload symptom questionnaire and the results of the genetic test (odds ratio: 1.17; 1.04-1.31; p < 0.01). CONCLUSIONS: The presence of diarrhoea and the symptom score after overload with 50 g lactose showed a higher degree of agreement and diagnostic accuracy for primary hypolactasia than the gaxilose test when the genetic test is used as a reference standard.

Low positive rate of serum autoantibodies in colorectal cancer patients without systemic rheumatic diseases.

BACKGROUND: Antinuclear antibody (ANA) testing is useful for screening, diagnosis and follow-up of patients with systemic rheumatic diseases. Indirect immunofluorescence (IIF) on HEp-2 cells is the gold standard for ANA testing. However, ANA have also been detected in patients with different cancer types but without any autoimmune disease. To overcome these shortcomings, different automated solid-phase assays have been developed. AIM: To determine the positive rate of a new ANA detection method (EliA CTD Screen, Phadia, Germany), in CRC patients without systemic rheumatic diseases. Additionally, we compare this method with IIF. MATERIALS AND METHODS: Serum samples were obtained before a colonoscopy procedure in a patient cohort (n = 186) with a high clinical suspicion of CRC. Samples for ANA detection in CRC patients were processed in parallel by IIF on HEp-2 and the solid-phase fluoroenzymeimmunoassay EliA CTD Screen (Phadia, Germany) on the Phadia 250 instrument (Phadia GmbH, Freiburg, Germany). Positive samples by IIF and/or CTD were tested with EliA single ANA assays (Phadia, Germany) on the Phadia 250 instrument (Phadia GmbH, Freiburg, Germany). RESULTS: Forty-five patients diagnosed with CRC were included. Four cases were positive by CTD and 23 by IIF. Of the four positive patients by CTD, two were positive and one indeterminate for anti-dsDNA antibodies. Of the 23 positive by IIF, one patient was positive and another indeterminate for anti-dsDNA antibodies, and a third patient was positive for anti-U1RNP antibodies. CONCLUSIONS: The CTD assay shows a low false positive rate for detecting autoantibodies in a clinical context of CRC.

Plasma Tumor M2-Pyruvate Kinase Levels in Different Cancer Types.

BACKGROUND/AIM: Tumor M2-pyruvate kinase (M2-PK) is up-regulated in proliferating tissues. It has been shown that tumor M2-PK is detectable and quantifiable in the stool and plasma of patients with colorectal cancer (CRC). Tumor M2-PK has been extensively studied in gastrointestinal tumors but its role in other cancer types has not yet been deeply evaluated. The aim of the study was to determine and compare plasma tumor M2-PK levels in different cancer types. MATERIALS AND METHODS: All patients undergoing diagnostics for cancer at our Hospital during 2011 were included in the study (n=139). Plasma tumor M2-PK concentration was analyzed by an enzyme-linked immunosorbent assay. RESULTS: The different cancer types found in the study were: 60 colorectal, 43 breast, 8 lung, 5 prostatic, 4 ovarian and the remaining 19 cases were other uncommon tumor types. Most tumors had high concentrations of tumor M2-PK; prostatic, pharyngeal and testicular tumors had levels lower than or near the cut-off. Plasma tumor M2-PK levels were significantly higher in patients with distant metastases and stage IV by TNM. CONCLUSION: Plasma tumor M2-PK is not a specific marker for CRC and is elevated in many other types of cancers, including breast, lung, ovarian, and thyroid. Small amounts are found in prostatic, pharyngeal and testicular tumors.

Masa ventricular izquierda, función diastólica y marcadores de metabolismo del colágeno en la hipertensión arterial refractaria / Left ventricular mass, diastolic function and collagen metabolism biomarkers in essential hypertension

Fundamento y objetivo: Evaluar la asociación entre biomarcadores del metabolismo del colágeno, índice de masa ventricular izquierda (IMVI) y función diastólica en pacientes con hipertensión arterial (HTA) refractaria. Pacientes y método:Se estudiaron 52 pacientes diagnosticados de HTA refractaria y se compararon con 24 individuos sanos. Se midió en suero el propéptido C-terminal de la molécula de procolágeno tipo I (PICP) y el factor de crecimiento transformante beta 1 (TGFβ1) por métodos de enzimoinmunoanálisis, y el telopéptido C-terminal del colágeno tipo I (ICTP) por inmunoensayo electroquimioluminiscente. A los pacientes se les practicó una ecocardiografía donde se calculó el IMVI por la fórmula de Devereux y se valoró la función diastólica a partir de la relación entre las ondas E y A (E/A) y la velocidad de propagación mitral. También se les practicó un registro de monitorización de la presión arterial (PA) de 24h. Resultados:Los hipertensos mostraron valores (media ±DE) superiores de PICP e inferiores de ICPT que los controles: 83,7 (24,7) frente a 55,0 (8,7), p<0,0001, y 175,0 (136,4) frente a 323,3 (121,3), p<0,0001. En los hipertensos existió una relación significativa entre el PICP y el IMVI (r=0,631, p<0,0001) y disfunción diastólica (r=-0,519, p<0,0001). Los grupos con y sin hipertrofia, y con o sin función diastólica, diferían en los citados péptidos pero no en las cifras de PA. Conclusiones: Nuestros hallazgos sugieren que diferentes marcadores de la síntesis y de la degradación del colágeno pueden relacionarse con la presencia de hipertrofia miocárdica o disfunción diastólica con independencia de las cifras de PA (AU)

To evaluate the association between circulating biomarkers of collagen metabolism in serum, left ventricular mass index (LVMI) and diastolic dysfunction in patients with resistant hypertension.Patients and methods: Fifty-two patients with resistant hypertension and 24 healthy individuals were included. The following biomarkers of collagen metabolism were analyzed by ELISA: carboxy-terminal propeptide of procollagen type I (PICP) and transforming growth factor beta1 (TGFβ1). The biomarker C-terminal telopeptide of collagen type-I (ICTP) was assayed by electrochemiluminescence immunoassay. In the patient's group a record of 24-h blood pressure monitoring was obtained and an echocardiography was performed. Left ventricular mass was measured according to the formula of Devereux and the diastolic function according to the relation of E and A waves and mitral propagation velocity. Results:Hypertensive patients showed higher levels of PICP and lower levels of ICTP than controls: 83.7 (24.7) vs. 55.0 (8.7), P<.0001; and 175.0 (136.4) vs. 323.3 (121.3), P<.0001). Hypertensive patients showed a significant relationship between PICP and LVMI (r=0.631, P<.0001) and between PICP and diastolic dysfunction (r=-0.519, P<.0001). The groups with and without hypertrophy, and with or without diastolic dysfunction, differed in the mentioned peptides but not in BP values. Conclusions:Our findings suggest that the analyzed markers of synthesis and degradation of collagen may be related to myocardial hypertrophy and diastolic dysfunction independent of blood pressure values (AU)

Prognostic value of plasmatic tumor M2 pyruvate kinase and carcinoembryonic antigen in the survival of colorectal cancer patients.

Colorectal cancer (CRC) can be cured in most cases if diagnosed at an early stage. Carcinoembryonic antigen (CEA) remains the most widely used cancer marker for determining prognosis of CRC. Previous studies have shown that plasmatic tumor M2 pyruvate kinase (Tu M2-PK) is highly sensitive in CRC detection at an early stage and equally as good as the results for established tumor markers with clinical potential for cancer prognosis and monitoring. The aim of this study was to assess the prognostic value of Tu M2-PK in plasma using a survival analysis in combination with CEA in serum in patients newly diagnosed with CRC. The initial study included 183 patients who had a complete diagnostic colonoscopy. This cohort study was designed to evaluate the survival in patients with histologically confirmed gastrointestinal cancers (n = 41). Tu M2-PK concentrations in EDTA plasma were determined immunologically using an ELISA assay. Plasma Tu M2-PK levels were significantly higher in patients with distant metastases, stage IV for TNM score, and advanced stage (C+D) subgroups of Dukes than other subgroups. The univariate Cox's analysis showed that CEA and Tu M2-PK gave high hazard ratios for risk of death (odds ratio CEA = 3.57 and odds ratioTu M2-PK = 2.23) and comparable values in average survival time. The results for both biomarkers did not overlap. These findings suggest that plasmatic Tu M2-PK levels of more than 20 U/mL may be a predictor of death risk.

[Left ventricular mass, diastolic function and collagen metabolism biomarkers in essential hypertension]. / Masa ventricular izquierda, función diastólica y marcadores de metabolismo del colágeno en la hipertensión arterial refractaria.

BACKGROUND AND OBJECTIVE: To evaluate the association between circulating biomarkers of collagen metabolism in serum, left ventricular mass index (LVMI) and diastolic dysfunction in patients with resistant hypertension. PATIENTS AND METHODS: Fifty-two patients with resistant hypertension and 24 healthy individuals were included. The following biomarkers of collagen metabolism were analyzed by ELISA: carboxy-terminal propeptide of procollagen type I (PICP) and transforming growth factor beta1 (TGFß1). The biomarker C-terminal telopeptide of collagen type-I (ICTP) was assayed by electrochemiluminescence immunoassay. In the patient's group a record of 24-h blood pressure monitoring was obtained and an echocardiography was performed. Left ventricular mass was measured according to the formula of Devereux and the diastolic function according to the relation of E and A waves and mitral propagation velocity. RESULTS: Hypertensive patients showed higher levels of PICP and lower levels of ICTP than controls: 83.7 (24.7) vs. 55.0 (8.7), P<.0001; and 175.0 (136.4) vs. 323.3 (121.3), P<.0001). Hypertensive patients showed a significant relationship between PICP and LVMI (r=0.631, P<.0001) and between PICP and diastolic dysfunction (r=-0.519, P<.0001). The groups with and without hypertrophy, and with or without diastolic dysfunction, differed in the mentioned peptides but not in BP values. CONCLUSIONS: Our findings suggest that the analyzed markers of synthesis and degradation of collagen may be related to myocardial hypertrophy and diastolic dysfunction independent of blood pressure values.

TGF-beta 1 y su relación con la hipertensión arterial esencial / Transforming growth factor-Beta1 in essential hypertension

Introducción. Se ha sugerido que los niveles plasmáticos elevados del factor de crecimiento transformante beta 1 (TGF-beta 1) juegan un papel clave para el desarrollo de las enfermedades que cursan con fibrosis. Objetivos. Este estudio observacional, transversal, retrospectivo de casos controles busca evaluar si existe asociación entre los niveles plasmáticos de TGF-beta 1 como factor causal en la patogénesis de la hipertensión arterial (HT-A) esencial y la lesión de órganos diana, en pacientes con HT-A esencial refractaria comparado con un grupo de sujetos sanos y comprobar si existe una correlación entre los niveles de TGF-beta 1 y los de PICP (propéptido C-terminal de la molécula de procolágeno tipo I), de degradación MMP-1 (metaloproteinasa de la matriz tipo 1) y degradación del colágeno ICTP (telopéptido C-terminal de la molécula de colágeno tipo I) en el grupo de sujetos hipertensos. Pacientes y métodos. Se estudiaron 52 pacientes diagnosticados de HT-A con edad media de 53 años y se comparó con grupo control de 24 voluntarios sanos con edad media de 45 años. TGF-beta 1 fue medido por método ELISA previa activación de la muestra. Resultados. Las concentraciones de TGF-beta 1 no fueron mayores en el grupo de hipertensos. La media±desviación estándar fue de 40±13 pg/mL, mientras que en el grupo control fue de 50±23 pg/mL. La t de Student no estableció diferencias significativas. Conclusiones. no se han encontrado niveles elevados de TGF-beta 1 en pacientes con hipertensión esencial en contra de lo evidenciado por otros autores. La exclusión en este estudio de pacientes que presentaban insuficiencia renal moderada o severa, asumimos que pudiera ser la causa de no encontrar elevados los niveles plasmáticos de TGF-beta (AU)

Introduction. It has been suggested that elevated serum transforming growth factor beta1 (TGF-beta 1) levels plays a key role to develope of diseases associated with fibrosis. Objective. This observational, transversal, retrospective case control study was designed to evaluate the association between TGF-beta 1 as causal factor for the hypertension arterial pathogenesis and damage on target organ. This study was designed to evaluate the association between circulating biomarkers of collagen metabolism and fibrosis in serum to compare TGF-beta1 levels obtained in a group of essential hypertension patients with a group of normotensive healthy subjects. Patients and methods. 46 essential hypertension patients, mean age: 53 years versus a control group of 20 healthy volunteers, mean age: 45 years. TGFâ1 was quantitated by a commercial ELISA technique, samples were previously activated. Results. TGF-beta 1 concentrations were not higher in essential hypertension patients, mean serum concentration (40±13ng/mL) than in normal group, mean serum concentration (50±23ng/mL). No significant differences were showed between two groups using t- student test. Conclusion. We have not found elevated TGF-beta 1 concentrations in essential hypertension patients in contrast to what has been shown by other authors. Exclusion of patients with mild or severe renal insufficiency should be considered to be a cause for not obtaining elevated TGF-beta 1 concentrations(AU)

Low utility of CYFRA 21-1 serum levels for diagnosis and follow-up in bladder cancer patients.

We evaluated serum levels of soluble fragments of cytokeratin 19 (CYFRA 21-1) by immunoassay (ES-700; Roche Diagnostics, Mannheim, Germany) to assess its usefulness in the diagnosis and follow-up of bladder cancer. The study included 39 patients with a diagnosis of transitional cell carcinoma (group 1) and 190 patients (group 2) with no evidence of tumor. In group 2, 180 patients had a history of bladder cancer, and 10 had benign prostatic hyperplasia. Significant differences in CYFRA 21-1 concentrations between groups 1 and 2 (P<0.01) were noted. However, CYFRA 21-1 levels did not significantly differ between the patients with benign prostatic hyperplasia and those with bladder cancer (P=0.274). CYFRA 21-1 values were higher in invasive bladder cancer compared to that detected in superficial stages (P=0.011). Setting the optimal cutoff value at 2.5 ng/mL resulted in a sensitivity of 43.6% and a specificity of 82.1%. No statistical differences were found when we compared disease-free time among the 66 patients with recurrences (30.7 months with levels <2.5 ng/mL vs. 41.2 months with levels >2.5 ng/mL; P=0.248). The risk of recurrence in patients with levels lower than 2.5 ng/mL (0.79) was no different (P=0.097) from that found in patients with higher levels (1.69). CYFRA 21-1 serum levels do not provide enough sensitivity to justify its application in routine protocols for the detection and follow-up of bladder cancer.