Endocan serum concentration in uninfected newborn infants.

INTRODUCTION: Endocan is a specific endothelial mediator involved in the inflammatory response. Its role in the diagnosis of sepsis has been studied in adult patients and late onset neonatal sepsis. The clinical signs of early onset sepsis (EOS) are nonspecific and routinely used biomarkers, such as C-reactive protein and procalcitonin, have low sensitivity, specificity and positive predictive value. Endocan could be useful as a biomarker for diagnosis of EOS, but at present normal range values for this molecule have not been reported. The aim of this study is to establish the normal values range for serum endocan in term and preterm newborns without risk factors for EOS and to characterize the variation pattern of its levels at different postnatal moments. METHODOLOGY: Mean endocan serum concentration (ESC) was measured in term and preterm newborns without clinical suspicion of EOS at different moments from birth. RESULTS: ESC (ng/mL) in term newborns was 1.74+/-0.13 on day 1 and 2.02+/-0.41 on day 3 respectively, (p=0.09). In preterm newborns ESC (ng/mL) was 2.02+/-0.11 and 1.97+/-0.18, (p=0.8) for day 1 and 3 respectively. ESC was not significantly influenced by sex, mode of delivery, evidence of fetal distress or presence of minor birth trauma. CONCLUSIONS: ESC (ng/mL) between the first and third day of life in either term or preterm infants don't appear to be significantly influenced by factors that are associated with elevation of inflammatory markers, thus using this biomarker for the diagnosis of EOS might reduce the false positive results.

Gene Expression Signatures Predictive of Bevacizumab/Erlotinib Therapeutic Benefit in Advanced Nonsquamous Non-Small Cell Lung Cancer Patients (SAKK 19/05 trial).

PURPOSE: We aimed to identify gene expression signatures associated with angiogenesis and hypoxia pathways with predictive value for treatment response to bevacizumab/erlotinib (BE) of nonsquamous advanced non-small cell lung cancer (NSCLC) patients. EXPERIMENTAL DESIGN: Whole-genome gene expression profiling was performed on 42 biopsy samples (from SAKK 19/05 trial) using Affymetrix exon arrays, and associations with the following endpoints: time-to-progression (TTP) under therapy, tumor-shrinkage (TS), and overall survival (OS) were investigated. Next, we performed gene set enrichment analyses using genes associated with the angiogenic process and hypoxia response to evaluate their predictive value for patients' outcome. RESULTS: Our analysis revealed that both the angiogenic and hypoxia response signatures were enriched within the genes predictive of BE response, TS, and OS. Higher gene expression levels (GEL) of the 10-gene angiogenesis-associated signature and lower levels of the 10-gene hypoxia response signature predicted improved TTP under BE, 7.1 months versus 2.1 months for low versus high-risk patients (P = 0.005), and median TTP 6.9 months versus 2.9 months (P = 0.016), respectively. The hypoxia response signature associated with higher TS at 12 weeks and improved OS (17.8 months vs. 9.9 months for low vs. high-risk patients, P = 0.001). CONCLUSIONS: We were able to identify gene expression signatures derived from the angiogenesis and hypoxia response pathways with predictive value for clinical outcome in advanced nonsquamous NSCLC patients. This could lead to the identification of clinically relevant biomarkers, which will allow for selecting the subset of patients who benefit from the treatment and predict drug response.

Serum mesothelin for diagnosing malignant pleural mesothelioma: an individual patient data meta-analysis.

PURPOSE: Mesothelin is currently considered the best available serum biomarker of malignant pleural mesothelioma. To examine the diagnostic accuracy and use of serum mesothelin in early diagnosis, we performed an individual patient data (IPD) meta-analysis. METHODS: The literature search identified 16 diagnostic studies of serum mesothelin, measured with the Mesomark enzyme-linked immunosorbent assay. IPD of 4,491 individuals were collected, including several control groups and 1,026 patients with malignant pleural mesothelioma. Mesothelin levels were standardized for between-study differences and age, after which the diagnostic accuracy and the factors affecting it were examined with receiver operating characteristic (ROC) regression analysis. RESULTS: At a common diagnostic threshold of 2.00 nmol/L, the sensitivities and specificities of mesothelin in the different studies ranged widely from 19% to 68% and 88% to 100%, respectively. This heterogeneity can be explained by differences in study population, because type of control group, mesothelioma stage, and histologic subtype significantly affected the diagnostic accuracy. The use of mesothelin in early diagnosis was evaluated by differentiating 217 patients with stage I or II epithelioid and biphasic mesothelioma from 1,612 symptomatic or high-risk controls. The resulting area under the ROC curve was 0.77 (95% CI, 0.73 to 0.81). At 95% specificity, mesothelin displayed a sensitivity of 32% (95% CI, 26% to 40%). CONCLUSION: In patients suspected of having mesothelioma, a positive blood test for mesothelin at a high-specificity threshold is a strong incentive to urge further diagnostic steps. However, the poor sensitivity of mesothelin clearly limits its added value to early diagnosis and emphasizes the need for further biomarker research.

Kinetics of soluble mesothelin in patients with malignant pleural mesothelioma during treatment.

RATIONALE: Previous data suggested that serum levels of soluble mesothelin (SM) are related to tumor size and may have prognostic significance in malignant pleural mesothelioma (MPM). OBJECTIVES: We tested the hypothesis that this marker could also be useful for monitoring response to treatment. METHODS: Serial measurements of SM were determined in 40 patients diagnosed with MPM and subjected to gene-transfer therapy using intrapleural infusion of an adenoviral vector expressing human IFN-beta or conventional treatment (mainly chemotherapy). MEASUREMENTS AND MAIN RESULTS: In patients with baseline SM levels greater than 1 nM/L and disease progression after therapy, SM levels increased by 2.1 nM/L at two, 5.2 nM/L at four and 1.3 nM/L at 6 months. Patients with initial SM below 1 nM/L had a similar but more moderate increase of SM over time. Patients who responded to treatment or were considered stable had an initial small decrease of SM followed by a return to baseline values after 6 months of follow-up. In patients with baseline SM levels greater than 1 nM/L, increasing levels were associated with a significantly shorter median survival than in patients with stable or decreasing SM levels (4.4 vs. 27.7 months; P = 0.012). CONCLUSIONS: Increasing serum levels of SM were associated with disease progression and worse outcome, whereas stable or decreasing values suggested response to treatment. If confirmed in larger series, SM could be used to monitor patients with malignant pleural mesothelioma under treatment.

Accuracy of clinical presentation for differentiating bacterial from viral meningitis in adults: a multivariate approach.

OBJECTIVE: To determine whether bacterial (BM) and viral (VM) meningitis can be differentiated based on initial clinical presentation. DESIGN AND SETTING: Retrospective cohort study in a medical emergency department and intensive care unit in a university hospital. PATIENTS: 144 adults, including 90 with confirmed BM and 54 unpretreated VM. MEASUREMENTS AND RESULTS: Symptoms, examination findings, paraclinical data, and clinical outcome were assessed. Severity was defined by the presence at referral of one of the following criteria: altered consciousness, seizures, focal neurological findings, and shock. After univariate analyses we performed stepwise logistic regression to determine predictors for BM available at referral (except for CSF Gram stain) and logistic regression using previously validated CSF cutoffs. Univariate methods identified the presence of one sign of severity as the most important predictor for BM (sensitivity 0.989, specificity 0.981, positive predictive value 0.989, negative predictive value 0.981, odds ratio 4,770) and showed that CSF results differ in BM and in VM (except for CSF glucose). Logistic regression analysis revealed severity and CSF absolute neutrophil count as the two predictors of BM (R2=0.876). Logistic analysis showed that BM was related to severity (beta=6.46+/-1.27) and a CSF absolute neutrophil count above 1,000/mm3 whereas CSF glucose below 2 mmol/l and CSF protein higher than 2 g/l were not predictive. CONCLUSIONS: The presence of at least one sign of severity at referral and a CSF absolute neutrophil count above 1,000/mm3 mm are predictive of BM.