| 1. |
- Carlson, Lena-Maria, et al.
(författare)
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The microenvironment of human neuroblastoma supports the activation of tumor-associated T lymphocytes.
- 2013
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Ingår i: Oncoimmunology. - : Informa UK Limited. - 2162-4011 .- 2162-402X. ; 2:3
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Tidskriftsartikel (refereegranskat)abstract
- Tumor infiltration by lymphocytes has been linked to improved clinical outcome in children with neuroblastoma (NB) but T-cell activation has never been demonstrated to occur within the NB microenvironment. Here we show that tumor-associated lymphocytes (TALs) obtained from lesions representing all genetic subsets of NB and autologous peripheral blood lymphocytes (PBLs) analyzed on the day of tumor excision differed in composition, phenotype and functional characteristics. The NB microenvironment appeared to promote the accumulation of CD3(+)CD8(+) T cells and contained a larger proportion of T cells expressing the interleukin-2 receptor α chain (CD25) and manifesting an effector memory (CCR7(-)CD45RA(-)) phenotype. Accordingly, the stimulation of PBLs with autologous tumor cells in short-term cultures increased the proportion of effector memory T cells, upregulated CD25, stimulated the expression of the TH1 cytokines interferon γ and tumor necrosis factor α, and reduced the expression of transforming growth factor β. In situ proliferation as well as a characteristic pattern of T-cell receptor aggregation at the contact sites with malignant cells was revealed by the immunohistochemical staining of TALs in primary tumors, indicating that the NB milieu is compatible with the activation of the immune system. Our results are compatible with the hypothesis that CD8(+) T cells are specifically activated within the NB microenvironment, which appears to be permissive for effector memory responses.
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| 2. |
- De Geer, Lina, et al.
(författare)
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Amino-terminal pro-brain natriuretic peptide as a predictor of outcome in patients admitted to intensive care. A prospective observational study
- 2012
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Ingår i: European Journal of Anaesthesiology. - : Lippincott, Williams and Wilkins / Wiley-Blackwell. - 0265-0215 .- 1365-2346. ; 29:6, s. 275-279
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Tidskriftsartikel (refereegranskat)abstract
- Context: Amino-terminal pro-brain-type natriuretic peptide is known to predict outcome in patients with heart failure, but its role in an intensive care setting is not yet fully established. Objective: To assess the incidence of elevated amino-terminal pro-brain natriuretic peptide (NT-pro-BNP) on admission to intensive care and its relation to death in the ICU and within 30 days. Design: Prospective, observational cohort study. Setting: A mixed noncardiothoracic tertiary ICU in Sweden. Patients and main outcome measures NT-pro-BNP was collected from 481 consecutive patients on admission to intensive care, in addition to data on patient characteristics and outcome. A receiver-operating characteristic curve was used to identify a discriminatory level of significance, a stepwise logistic regression analysis to correct for other clinical factors and a Kaplan-Meier analysis to assess survival. The correlation between Simplified Acute Physiology Score (SAPS) 3, Sequential Organ Failure Assessment score (SOFA) and NT-pro-BNP was analysed using Spearmans correlation test. Quartiles of NT-pro-BNP elevation were compared for baseline data and outcome using a logistic regression model. Results: An NT-pro-BNP more than 1380 ng l(-1) on admission was an independent predictor of death in the ICU and within 30 days [odds ratio (OR) 2.6; 95% confidence interval (CI), 1.5 to 4.4] and was present in 44% of patients. Thirty-three percent of patients with NT-pro-BNP more than 1380 ng l(-1), and 14.6% of patients below that threshold died within 30 days (log rank P 0.005). NT-pro-BNP correlated moderately with SAPS 3 and with SOFA on admission (Spearmans rho 0.5552 and 0.5129, respectively). In quartiles of NT-pro-BNP elevation on admission, severity of illness and mortality increased significantly (30-day mortality 36.1%; OR 3.9; 95% CI, 2.0 to 7.3 in the quartile with the highest values, vs. 12.8% in the lowest quartile). Conclusion: We conclude that NT-pro-BNP is commonly elevated on admission to intensive care, that it increases with severity of illness and that it is an independent predictor of mortality.
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