A phase II pharmacodynamic study of erlotinib in patients with advanced non-small cell lung cancer previously treated with platinum-based chemotherapy.

PURPOSE: To examine potential markers of clinical benefit and the effects of erlotinib on the epidermal growth factor receptor (EGFR) signaling pathway in advanced non-small cell lung cancer patients refractory to platinum-based chemotherapy. EXPERIMENTAL DESIGN: Patients were given erlotinib (150 mg/d). Tumor biopsies were done immediately before treatment and in a subgroup of patients after 6 weeks' treatment. RESULTS: Of 73 evaluable patients, 7 (10%) had partial response and 28 (38%) had stable disease. In 53 patients with baseline tumor samples, no relationship was observed between pretreatment levels of EGFR, phosphorylated (p)-EGFR, p-AKT, p-mitogen-activated protein kinase (MAPK), or p27 and clinical benefit (i.e., response, or stable disease >/=12 weeks). Tumors from 15 of 57 patients had high EGFR gene copy number, assessed using fluorescence in situ hybridization (FISH positive), 10 of whom had clinical benefit, compared with 5 of 42 FISH-negative patients. FISH-positive patients had longer median progression-free [137 versus 43 days, P = 0.002; hazard ratio (HR), 0.37] and overall (226 versus 106 days, P = 0.267; HR, 0.70) survival than FISH-negative patients. In paired biopsy samples from 14 patients, p-EGFR (P = 0.002), p-MAPK (P = 0.001), and Ki-67 (P = 0.025) levels were significantly reduced after 6 weeks' treatment. Apoptosis was significantly increased in patients with clinical benefit (P = 0.029), and may be a marker of clinical benefit. CONCLUSION: In this study, EGFR FISH-positive status was associated with improved outcome after erlotinib therapy. Erlotinib led to reduced levels of p-EGFR, p-MAPK, and Ki-67, and stimulated apoptosis in tumor samples from patients with clinical benefit.

Parafac and go/no-go: disentangling CNV return from the P3 complex by trilinear component analysis.

It has been proposed that the fronto-central difference between go-P3 and no-go P3 is due to motor-related negativity overlapping P3 in the go case and positive relaxation of such negativity overlapping P3 in the no-go case, and that this motor-related activation may be identified by its having the same topography as the preceding CNV. Testing these suggestions meets with the problem of how to validly distinguish between P3 and the assumed overlapping continuing or downsweeping CNV. Distinguishing between overlapping components is a major reason why principal component analysis (PCA) has been applied, but the major criterion of conventional rotations (Varimax and Promax) is avoiding overlap. Trilinear component analysis (TCA) defines components independently of overlap, by their having stable topographies across time and observations. By applying TCA, we expected to obtain equal P3 components in go and no-go, and a preceding CNV component that would continue and overlap P3 with negative polarity in the go case and with positive polarity in the no-go case. We analyzed data from warned go/no-go tasks, separately for blocks with hand movements and eye movements. Different from expectation, TCA of the Hand task yielded three relevant components: parietal P3, only slightly affected by go vs. no-go, an overlapping CNV downturn unaffected by go vs. no-go, and an anterior-positive/posterior-negative bipolar N2-P3 that modeled the go/no-go effect. No convincing TCA solution was obtained in the Eye task. Possibilities and limitations of the TCA method are discussed.

N-terminal pro brain natriuretic peptide in the management of patients in the medical emergency department (PROMPT): correlation with disease severity, utilization of hospital resources, and prognosis in a large, prospective, randomized multicentre trial.

AIMS: N-terminal pro brain natriuretic peptide (NT-proBNP) is a potent marker of heart failure and other cardiac diseases. The value of NT-proBNP testing in the medical emergency department (ED) was assessed in patients >65 years old. METHODS AND RESULTS: This large, prospective, randomized, controlled, multicentre trial was conducted in six medical EDs. Data for evaluation of the primary endpoint of hospitalization were available for 1086 patients. Median NT-proBNP was 582 pg/mL. A total of 16% of patients presented with NT-proBNP <150 pg/mL (low), 55% with NT-proBNP between 150 and 1800 pg/mL (intermediate), and 29% with NT-proBNP >1800 pg/mL (high). NT-proBNP was positively correlated with hospital admission [ odds ratio (OR) for high vs. low 2.9, P < 0.0001], length of stay (8.5 days vs. 3.5 days for high vs. low, P < 0.01), in-hospital death (3.9% vs. 0% for high vs. low, P < 0.01), 6 months re-hospitalization (OR for high vs. low 5.1, P < 0.0001), and 6 months death or re-hospitalization (OR for high vs. low 5.7, P < 0.0001). Knowledge of NT-proBNP had no significant effect on the primary endpoint hospital admission and the secondary endpoints intermediate/intensive care unit (IMC/ICU) admission, length of stay, re-hospitalization and death, or re-hospitalization in the total cohort. However, patients with high open NT-proBNP (>1800 pg/mL) were more likely to be admitted to the hospital (P < 0.05) and IMC/ICU (P < 0.05), whereas patients with low open NT-proBNP (<150 pg/mL) were less likely to be admitted (P < 0.05) compared with patients with blinded NT-proBNP. CONCLUSION: Although NT-proBNP does not affect overall hospitalization, it is associated with better stratification of patient care and is strongly correlated with subsequent utilization of hospital resources and prognosis.

Tasas de supervivencia en pacientes con enfermedad renal. Influencia de la corrección de la anemia / Survival rates in patients with kidney disease. influence of the anemia correction

Las ventajas de la corrección de la anemia en pacientes que se encuentran en tratamiento con diálisis son conocidas. Estos beneficios, relacionados con la elevación de los niveles de hemoglobina, probablemente se manifiesten también en quienes padecen nefropatía crónica.