CA 15-3 as an alternative marker for KL-6 in fibrotic lung diseases.

BACKGROUND: KL-6 is a mucin that is increased in interstitial lung diseases (ILD), and in some malignancies. CA 15-3, a tumor marker for breast cancer, refers to the same mucin but utilizes antibodies against different epitopes. OBJECTIVE: The aim of our study was to evaluate CA 15-3 as a viable alternative to KL-6 as a for ILDs with and without fibrosis. DESIGN: Serum from 242 patients with ILDs and from 327 healthy controls were included and KL-6 and CA 15-3 were measured in all subjects. Regression analyses and ROC curves were used to compare the performances of both markers. RESULTS: KL-6 and CA 15-3 levels were both significantly higher in the ILD patients compared to the controls (p < 0.0001). A weak yet significant correlation was found between serum KL-6 and CA 15-3 levels in the controls (R = 0.39, p < 0.0001), but showed a much higher correlation in the patient group (R = 0.85, p < 0.0001). CA 15-3 correlated best with KL-6 in patients with fibrotic ILDs (R = 0.83, p < 0.0001). KL-6 performed better as a marker compared to CA 15-3 in most ILDs. Both markers performed best in identifying idiopathic pulmonary fibrosis (IPF) and were equally able to differentiate between ILDs with and without fibrosis: (sensitivity and specificity %): 100/97, 95/92, and 90/72, respectively. CONCLUSION: CA 15-3 and KL-6 are equally sensitive and specific in terms of differentiating between ILDs with and without fibrosis. The wide availability, ease of use, and cost effectiveness, make CA 15-3 a viable alternative for KL-6 as a possible marker for pulmonary fibrosis.

Inhibition of platelet function by abciximab or high-dose tirofiban in patients with STEMI undergoing primary PCI: a randomised trial.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI, few data exist on the magnitude of platelet activation, aggregation and dosing of glycoprotein (GP) IIb/IIIa receptor inhibitors. METHODS: Sixty STEMI patients were randomised to abciximab, to high-dose tirofiban or to no additional GP IIb/IIIa inhibitor treatment. Platelet activation (P-selectin expression) was measured using flow cytometry and the level of inhibition of platelet aggregation was assessed using the Plateletworks assay. Additionally, the PFA-100 with the collagen/adenosine-diphosphate cartridge (CADP) was used to compare the levels of platelet inhibition. All measurements were performed at baseline (T(0)), immediately after (T(1)), 30 minutes (T(2)), 60 minutes (T(3)) and 120 minutes (T(4)) after primary PCI. RESULTS: The level of platelet activation in both GP IIb/IIIa receptor inhibitor treated groups was significantly lower compared with the control group at all time points after primary PCI (p=0.04). Also the administration of the currently recommended dose of abciximab resulted in significantly lower levels of inhibition of aggregation compared with high-dose tirofiban (p<0.0001). In addition, the CADP closure times were significantly prolonged in both GP IIb/IIIa inhibitor treated groups compared with the control group at time points T(1) (p=0.006) and T(4) (p<0.0001). CONCLUSION: The administration of high-dose tirofiban resulted in a significantly higher inhibition of platelet aggregation compared with the currently recommended dose of abciximab. Large clinical trials are needed to assess whether this laboratory superiority of high-dose tirofiban translates into higher clinical efficacy. (Neth Heart J 2007;15:375-81.).

Pneumoproteins as a lung-specific biomarker of alveolar permeability in conventional on-pump coronary artery bypass graft surgery vs mini-extracorporeal circuit: a pilot study.

BACKGROUND: Despite improvements of the heart-lung machine (HLM), oxidative stress and subsequent damage to the alveolar capillary membrane still occur after conventional on-pump coronary artery bypass graft (CCABG) surgery. In an attempt to further improve the conventional HLM, a mini-extracorporeal circuit (MECC) was introduced. This new concept is based on minimal volume shifts. The extent of alveolar injury that is associated with this new technique is unknown. The lung-specific biomarkers Clara-cell 16 (CC16) and KL-6 are applied in this study to quantify alveolar dysfunction in both techniques. METHODS: In a prospective observational setting, the concentrations of CC16 and KL-6 were measured during and after 10 consecutive CCABG operations and 10 consecutive coronary artery bypass graft (CABG) operations using MECC (MCABGs). These pneumoproteins were measured after the induction of anesthesia, before clamping of the ascending aorta, after unclamping of the aorta, on arrival to the ICU, and on the following days until discharge. Quantification of the differences of KL-6 and CC16 leakage through the alveolar membranes between the two techniques was realized by calculation of the Student t test. Perioperative and postoperative shunt fractions and clinical observations were monitored simultaneously. The potential value of pneumoproteins as biomarkers for quantification of alveolar permeability during CABG surgery was tested. RESULTS: Significantly reduced concentrations of CC16 were found early after MCABG as compared to CCABG surgery (p = 0.033). KL-6 showed no consistent pattern during both treatment modalities. Early after CCABG surgery, shunt fractions tended to show reduced oxygen transport over the alveolar membrane as compared to MCABG surgery. CONCLUSION: CC16 appears to be a useful biomarker for alveolar permeability during CABG surgery. Injury of the alveolar capillary membrane appears significantly reduced during MCABG surgery. Consistently early postoperative alveolar shunt fractions showed an increased value in CCABG compared to MCABG surgery in the early postoperative phase. Further randomized studies need to confirm the value of CC16 as marker in monitoring alveolar capillary damage during coronary bypass grafting.

The usefulness of five D-dimer assays in the exclusion of deep venous thrombosis.

D-Dimer measurement is a promising tool in the exclusion of venous thrombosis. New d-dimer assays have been introduced, but need clinical validation. Our objective was to evaluate the clinical usefulness of four relatively new d-dimer assays and a classical ELISA in outpatients suspected for deep venous thrombosis. In 537 patients, participants in a large prospective management study using a clinical probability score and a d-dimer measurement (Tina-quant), additional samples were taken for d-dimer measurement using the Asserachrom ELISA, the VIDAS New, the STA-LIA and the Miniquant assay. Performances of each test were calculated using clinical data during a 3-month follow-up. Thrombosis was detected in 224 patients (42%). The area under the ROC curve was significantly higher for the Tina-quant as compared to the other assays. Using standard cut-off values, sensitivity, negative predictive value (NPV) and specificity of the Asserachrom were 97, 94 and 33%, respectively. For the VIDAS New, values were 100, 96 and 8%, respectively. The Tina-quant showed values of 99, 98 and 41%, respectively, and the STA-LIA 98, 95 and 32%. Values for the Miniquant were 95, 94 and 52%. The d-dimer assays in our study all show a high sensitivity and negative predictive value, but none of the assays reached an NPV of > 98% at standard cut-off values. d-Dimer assays with a low specificity still necessitate additional diagnostic tests in the majority of the patients.

S100 protein content of umbilical cord blood in healthy newborns in relation to mode of delivery.

BACKGROUND: Early detection and quantification of brain damage in neonatal asphyxia is important. In adults, S100 protein in blood is associated with damage to the central nervous system. OBJECTIVE: To determine whether S100 protein can be detected in arterial and venous cord blood of healthy newborns and to relate S100 protein concentrations in cord blood to mode of delivery. METHOD: S100 protein levels in umbilical cord blood of 81 healthy infants were determined. RESULTS: S100 protein was present in arterial (median concentration 1.62 micro g/l) and venous (median concentration 1.36 micro g/l) cord blood. Levels were significantly higher in vaginal births (median arterial concentration 1.72 micro g/l; median venous concentration 1.48 micro g/l) than births by caesarean section (1.51 micro g/l and 1.26 micro g/l respectively). CONCLUSION: More research is necessary to determine whether S100 protein is a useful marker in neonatal asphyxia.