Background: Recent evidence confirms the importance of both biological and pathological risk markers in predicting early relapse for breast cancer patients treated with endocrine therapy. Most studies use a two step process integrating biological markers into a “biological predictor (e.g. Oncotype Dx, “IHC4” etc) followed by assessment of the predictive value of such tests in the context of pathological markers (grade, nodal status etc). We have taken a one step process integrating both biological and pathological markers into a single model to assess key factors for predicting outcome at 2.75 years and 5 years of endocrine therapy; to inform choices between switching, upfront and extended adjuvant treatment with AIs. Patients & Methods: Pathology blocks from 4598 TEAM patients were collected and tissue microarrays constructed. Quantitative analysis ER, PgR, Ki67, HER1, HER2, and HER3 was performed centrally. A prognostic model, integrating data from biological and pathological markers was created to assess risk (disease-free survival) after 2.75 and 5 years of follow up in the TEAM trial. Results: Of 4595 eligible cases samples received, 16 were excluded, and 3993 had complete biomarker data for all markers for the final biomarker analysis. In univariate analysis nodal status, grade, size, age at diagnosis, HER1, HER2, PgR, ER and Ki67 were all prognostic. At 2.75 years nodal status, age, PgR histoscore, size, grade, HER2, ER histoscore and HER1 positivity were significant prognostic variables (ranked by WaldX2 statistic), Ki67 and HER3 were not included in this model. At 5 years median follow up; age, nodal status, size, PgR histoscore, grade, Ki67, HER2, and HER1 positivity were significant prognostic variables (ranked by WaldX2 statistic), ER and HER3 were not included in this model. Conclusion: Combined biological and pathological marker panels are of significant value in predicting early relapse in breast cancer patients treated with endocrine therapy, however duration of follow-up may impact on the inclusion of variables in the model. This provides significant information relevant to the choice of different adjuvant endocrine therapies. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-04.
Background Among chickens, meat producing broiler strains are highly prone to develop severe pulmonary hypertension (PH) associated with endothelial dysfunction. However, pulmonary endothelial function appears to be unaffected during prenatal life.Objective To test the hypothesis that exposure to chronic prenatal hypoxia induces endothelial impairment and accelerates the development of PH in chickens prone to the disease.Methods Fertilized eggs from two genetic lines of broiler chickens differing in susceptibility to PH (high sensitivity: HS, low sensitivity: LS) were incubated under normoxic or hypoxic (15% O2) conditions from day 6 to day 19 of a 21-d incubation period. On day 19 isolated intrapulmonary artery segments were mounted in a myograph for isometric tension recording. The contractile responses induced by KCl as well as the relaxations induced by acethylcholine (ACh), the nitric oxide donor sodium nitroprusside (SNP), and the adenylate cyclase activator forskolin were tested.Results Hypoxia produced a reduction in the weight of the HS (31.1 Ϯ 0.6 g vs 27.3 Ϯ 0.6 g, PϽ0,001) and the LS (32.1Ϯ 0.6 vs 28.6 Ϯ 0.9 PϽ0,001) embryos. KCl-induced contraction was unaffected by hypoxia in both groups. Endothelium-dependent (induced by ACh) and -independent (induced by SNP and forskolin) relaxations were also unaffected by hypoxia in both groups. AChinduced relaxation was reduced by the NO synthase inhibitor L-NAME (10 mM) and abolished by the soluble guanylyl cyclase inhibitor ODQ (10 microM). L-NAME induced inhibition of ACh-induced relaxation was less marked in normoxic embryos of the HS group than in the other three groups.Conclusions Chronic hypoxia during incubation reduced embryonic growth but did not influence vascular reactivity in chicken embryos prone to postnatal pulmonary hypertension. INTESTINAL PERMEABILITY AND MECHANICAL VENTILATION IN PRE-TERM INFANTS CONCLUSIONS. IN CONTRAST TO OUR HYPOTHESIS, WE DID NOT FIND A HIGHER INTESTINAL PERMEABILITY IN MECHANICAL VENTILATED INFANTS COMPARED TO NON-VENTILATED INFANTS, MEASURED Ͻ48 H AFTER BIRTH. FURTHERMORE, WE DID NOT FIND A SMALLER DECREASE IN INTESTINAL PERMEABILITY IN THE FIRST WEEK OF LIFE IN VENTILATED INFANTS COMPARED TO NON-VENTILATED INFANTS. FURTHER STUDIES ARE NEEDED TO ELUCIDATE THE EFFECT OF MECHANICAL VENTILATION ON INTESTINAL PERMEABILITY IN PRETERM INFANTS. FOLLOW UP AFTER AABR NEONATAL HEARING SCREENING IN NICU GRADUATES.HLM VAN Goal To explore the severity and type of bilateral HL as wel as the prognostic value of the first diagnostic BERA.Methods NICU graduates with bilateral HL from one NICU (Zwolle) were included. Severity of HL was established as mild (20 -39dB), moderate (40 -59dB), severe (60 -90 dB) or profound (Ͼ90dB). Type of HL was conductive, perceptive, combined, or auditory neuropathy. Improvement of Ͼ 20 dB between the first BERA and observation audiometry at Ͼ 2 years at follow up was considered as clinically relevant.Results Severity of HL after first diagnostic BERA of 37 newborns with bilateral HL was 6 mild, 7 mo...
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