Serum Chemokine-release Profiles in AML-patients Might Contribute to Predict the Clinical Course of the Disease.

In cancer or hematologic disorders, chemokines act as growth- or survival factors, regulating hematopoiesis and angiogenesis, determining metastatic spread and controlling leukocyte infiltration into tumors to inhibit antitumor immune responses. The aim was to quantify the release of CXCL8, -9, -10, CCL2, -5, and IL-12 in AML/MDS-pts' serum by cytometric bead array and to correlate data with clinical subtypes and courses. Minimal differences in serum-levels subdivided into various groups (e.g. age groups, FAB-types, blast-proportions, cytogenetic-risk-groups) were seen, but higher release of CXCL8, -9, -10 and lower release of CCL2 and -5 tendentially correlated with more favorable subtypes (<50 years of age, <80% blasts in PB). Comparing different stages of the disease higher CCL5-release in persisting disease and a significantly higher CCL2-release at relapse were found compared to first diagnosis - pointing to a change of 'disease activity' on a chemokine level. Correlations with later on achieved response to immunotherapy and occurrence of GVHD were seen: Higher values of CXCL8, -9, -10 and CCL2 and lower CCL5-values correlated with achieved response to immunotherapy. Predictive cut-off-values were evaluated separating the groups in 'responders' and 'non-responders'. Higher levels of CCL2 and -5 but lower levels of CXCL8, -9, -10 correlated with occurrence of GVHD. We conclude, that in AML-pts' serum higher values of CXCL8, -9, -10 and lower values of CCL5 and in part of CCL2 correlate with more favorable subtypes and improved antitumor'-reactive function. This knowledge can contribute to develop immune-modifying strategies that promote antileukemic adaptive immune responses.

Conversion of AML-blasts to leukemia-derived dendritic cells (DCleu) in 'DC-culture-media' shifts correlations of released chemokines with antileukemic T-cell reactions.

Dendritic cells (DC) and T-cells are mediators of CTL-responses. Autologous (from patients with acute myeloid leukaemia (AML) or myelodysplasia (MDS)) or allogeneic (donor)-T-cells stimulated by DCleu, gain an efficient lysis of naive blasts, although not in every case. CXCL8, -9, -10, CCL2, -5 and Interleukin (IL-12) were quantified by Cytometric Bead Array (CBA) in supernatants from 5 DC-generating methods and correlated with AML-/MDS-patients' serum-values, DC-/T-cell-interactions/antileukemic T-cell-reactions after mixed lymphocyte culture (MLC) and patients' clinical course. The blast-lytic activity of T-cells stimulated with DC or mononuclear cells (MNC) was quantified in a cytotoxicity assay. Despite great variations of chemokine-levels, correlations with post-stimulation (after stimulating T-cells with DC in MLC) improved antileukemic T-cell activity were seen: higher released chemokine-values correlated with improved T-cells' antileukemic activity (compared to stimulation with blast-containing MNC) - whereas with respect to the corresponding serum values higher CXCL8-, -9-, and -10- but lower CCL5- and -2-release correlated with improved antileukemic activity of DC-stimulated (vs. blast-stimulated) T-cells. In DC-culture supernatants higher chemokine-values correlated with post-stimulation improved antileukemic T-cell reactivity, whereas higher serum-values of CXCL8, -9, and -10 but lower serum-values of CCL5 and -2 correlated with post-stimulation improved antileukemic T-cell-reactivity. In a context of 'DC'-stimulation (vs serum) this might point to a change of (CCL5 and -2-associated) functionality from a more 'inflammatory' or 'tumor-promoting' to a more 'antitumor'-reactive functionality. This knowledge could contribute to develop immune-modifying strategies that promote antileukemic (adaptive) immune-responses.

Nutritional assessment and management in hospitalised patients: implication for DRG-based reimbursement and health care quality.

INTRODUCTION: Malnutrition is associated with a higher morbidity resulting in an increased need for medical resources and economic expenses. In order to ensure sufficient nutritional care it is mandatory to identify the effect of malnutrition and nutritional care on direct cost and reimbursement. The primary aim of this study was to evaluate the economic effect of a nutritional screening procedure on the identification and coding of malnutrition in the G-DRG system. METHODS: All G-DRG relevant parameters of 541 consecutive patients at a gastroenterology ward were documented. Moreover, all patients were screened for malnutrition by a dietician according to the subjective global assessment (SGA). Patients were then grouped into the appropriate G-DRG and the effective cost weight (CW) was calculated. RESULTS: Ninety-two of 541 patients (19%) were classified malnourished (SGA B or C). Recognition of malnutrition increase from 4% to 19%. Malnourished patients exhibited a significantly increased length of hospital stay (7.7+/-7 to 11+/-9, P<0.0001). In 26/98 (27%) patients, the coding of malnutrition was considered relevant by grouping and resulted in a rise of DRG benefit. Mean case mix value and patients' complexity and comorbidity level (PCCL) increased after including malnutrition in the codification (CV 1.53+/-2.9 to 1.65+/-2.9, P=0.001 and PCCL 2.69+/-1.4 to 3.47+/-0.82, P<0.0001). The reimbursement increase by 360/malnourished patient or an additional reimbursement of 35280 (8.3% of the total reimbursement for all patients of 423186). Nutritional support in a subgroup of 50 randomly selected patients resulted in additional costs of 10268 . Forty-four of these patients (86%) were classified malnourished (32 SGA B and 12 SGA C). However, the subsequent reimbursement covered only approximately 75% of the expenses (7869), but did not include the potential financial benefits resulting from clinical interventions. CONCLUSION: Malnourished patients can be detected with a structured assessment and documentation of nutritional status and this is partly reflected in the G-DRG/ICD 10 system. In addition to increasing direct health care reimbursement, nutritional screening and intervention has the potential to improve health care quality.