A risk score for predicting perioperative blood transfusion in liver surgery.

BACKGROUND: It would be desirable to predict which patients are most likely to benefit from preoperative autologous blood donation. This aim of this study was to develop a point scoring system for predicting the need for blood transfusion in liver surgery. METHODS: The medical records of 480 consecutive patients who underwent hepatic resection were analysed. The data set was split randomly into a derivation set of two-thirds and a validation set of one-third. Univariable analysis was carried out to determine the association between clinicopathological factors and blood transfusion. Significant variables were entered into a multiple logistic regression model, and a transfusion risk score (TRS) was developed. The accuracy of the system was validated by calculating the area under the receiver-operator characteristic (ROC) curve. RESULTS: Factors associated with blood transfusion in multivariable analysis included preoperative haemoglobin concentration below 12.5 g/dl, largest tumour more than 4 cm, need for exposure of the vena cava, need for an associated procedure, and cirrhosis. Each variable was assigned one point, and the total score was compared with the transfusion status of each patient in the validation set. The TRS accurately predicted the likelihood of blood transfusion. In the validation set the area under the ROC curve was 0.89. CONCLUSION: Use of the TRS could lead to substantial saving by improving the cost-effectiveness of the autologous blood donation programme.

Rapamycin induces a caspase-independent cell death in human monocytes.

The immunosuppressive activity of rapamycin (RAPA) and its efficacy as an anti-rejection agent in organ transplantation have been ascribed principally to its anti-proliferative effects on T cells, while the activity on monocytes is partially unknown. In vitro, RAPA reduced monocyte survival by inducing a caspase-independent cell death. RAPA-induced monocyte cell death (RAPA-CD) was impeded by activation of granulocyte macrophage-colony stimulating factor family receptors or toll-like receptor 4, and by exposure to inflammatory cytokines. In vivo, in patients who received RAPA monotherapy as part of pre-conditioning for islet transplantation, RAPA affected survival of myeloid lineage cells. In the peripheral blood, CD33(+) and CD14(+) cells decreased, whereas lymphocytes appeared unaffected. In the bone marrow, myeloid precursors such as CD15(+) and CD15(+)/CD16(+) were selectively and significantly decreased, but no major cytotoxic effects were observed. The RAPA-CD suggests a dependence of monocytes on mammalian target of RAPA pathways for nutrient usage, and this feature implies that RAPA could be selectively useful as a treatment to reduce monocytes or myeloid cells in conditions where these cells negatively affect patient, suggesting a potential anti-inflammatory action of this drug.

Serum CA 125 is of clinical value in the staging and follow-up of patients with non-Hodgkin's lymphoma: correlation with tumor parameters and disease activity.

BACKGROUND: CA 125 is a glycoprotein produced by epithelial ovarian tumors and by mesothelial cells; its levels also have been shown to be elevated in patients with non-Hodgkin's lymphoma (NHL). METHODS: The authors evaluated serum CA 125 levels in patients with NHL to elucidate the frequency of this finding, its relationship with other presenting features, and its potential role as tumor marker. One hundred and fifty-seven patients underwent the first CA 125 assessment at onset, 54 at disease recurrence or progression, and 62 during complete remission (CR). RESULTS: Of the 157 patients evaluated at diagnosis (median CA 125: 26 U/mL; range, 2-1400 U/mL), 63 (40%) had increased CA 125 values. Higher CA 125 levels were associated with advanced disease, aggressive histology, mediastinal and/or abdominal involvement, bulky tumor, high tumor burden, effusions, contiguous extranodal extension, high serum lactate dehydrogenase (LDH) activity, and elevated beta2-microglobulin (beta2-M) levels. Parameters identified by multivariate analysis to be independently associated with high CA 125 were: aggressive histology, mediastinal and/or abdominal disease, bulky tumor, high serum LDH activity and beta2-M serum levels, and the presence of effusion (P = 0.0000; explained variation = 0.64). Of the patients presenting with abnormal CA 125 levels, all those who achieved a CR (35) and 3 of the 6 who achieved a partial response had normalization of CA 125 values by the end of treatment. Conversely, CA 125 remained above normal values in 18 nonresponders. All 62 patients evaluated during CR showed normal CA 125 levels. Among patients first evaluated at disease recurrence or progression, 22 of 54 (41%) showed increased CA 125 levels, which were associated with the same parameters of disease found in patients examined at diagnosis. CONCLUSIONS: High serum CA 125 levels were found to correlate with mediastinal and/or abdominal involvement, high tumor mass, and effusions, reflecting the reaction of mesothelial cells to the tumor. Serum CA 125 is a reliable biologic marker for the staging and restaging of patients with lymphoma. Serial measurements are useful, in conjunction with other markers, for monitoring response to treatment.

Bone marrow T-cell subsets in patients with monoclonal gammopathies: correlation with clinical stage and disease status.

BACKGROUND AND OBJECTIVE: The existence of an imbalance in T-cell subpopulations in patients (pts) affected by monoclonal gammopathies (MG) has been well established. This imbalance might be correlated with different control of plasma cell growth and, particularly in MM, with the severity of the disease. The aim of this study was to verify whether the alteration of the T lymphocyte subsets in bone marrow correlates with the diagnosis, clinical status and disease phase in patients with monoclonal gammopathies. METHODS: We performed a study on bone marrow (BM) T-cell subsets in 49 multiple myelomas (MM) and in 17 monoclonal gammopathies of uncertain significance (MGUS), using as controls 20 BM aspirates from normal subjects. RESULTS: The percentages of BM CD4 cells in MM pts at onset were slightly lower than in controls and in MGUS pts, who showed normal percentages of CD4. The percentages of CD8 cells were lower than in controls in both MM and MGUS (p = 0.02 and p = 0.007, respectively), and consequently the CD4/CD8 ratios were significantly higher than in normal subjects (p = 0.01 and 0.008, respectively). Analysis of BM T-cell subpopulations in MM pts showed a progressive decrease in the percentage of CD4 cells from stage I to stage III (I vs III p = 0.008) and an increase in CD8 cells, although not statistically significant. The same trend was observed when the different phases of MM (onset, plateau, progression) were analyzed: a lower percentage of CD4 cells and an increase of CD8 cells characterized the advanced phases. Treatment did not seem to alter significantly the distribution of T-cell subsets in MM patients. INTERPRETATION AND CONCLUSIONS: The imbalance in T-cell involving the bone marrow lymphocytic populations that exist in MG is somewhat different in MGUS and MM. In MM patients this disturbance is related to the disease stages and phases, reflecting an important role for T-cell subsets in tumor cell control.