Cytokines clearance during venovenous hemofiltration in the trauma patient.

The objective of the study was to investigate whether continuous venovenous hemofiltration (CVVH) would facilitate removal of substantial amounts of tumor necrosis factor (TNF) and interleukin-6 (IL-6) from the circulation in traumatized critically ill patients with multiple organ dysfunction syndrome. The study design was a prospective, nonblind, randomized controlled trial that was set in the trauma intensive care unit of a tertiary university referral hospital. Thirty consecutive critically ill, mechanically ventilated trauma patients with multiple organ dysfunction syndrome (without renal failure) were included in the study. Patients were randomized to either CVVH or conventional treatment. Blood and ultrafiltrate samples were collected from each patient before the initiation of CVVH and after 24, 72, and 168 hours of therapy. In the control group, blood samples were collected during the same periods. In the 30 patients studied, 15 had hemofiltration and 15 did not. Both groups were similar with regard to age (36+/-18 years v 36+/-14 years) and severity scores (injury severity score, 32+/-16 v 30+/-11; APACHE II score, 22+/-7 v 21+/-6; Goris score, 5.2+/-1.7 v 5.2+/-1.8). Before CVVH, TNF and IL-6 could be detected in the serum of all patients. The mean concentration of TNF was 17+/-22 pg/mL in patients and 22+/-20 pg/mL in control subjects (P = NS). The mean concentration of IL-6 was 2,153+/-2,824 pg/mL in patients and 1,774+/-1,637 pg/mL in control subjects (P = NS). We found a TNF and IL-6 substantial elimination with CVVH (excretion of TNF [microg/d] at 24, 48, and 168 hours: 112.6+/-161.2, 105.2+/-149.4, and 143.1+/-170.0; excretion of IL-6 [microg/d]: 1,655+/-719, 3,091+/-489, and 2,420+/-366). However, no significant difference was found in serum cytokines concentration between groups during the study: mean serum TNF concentration decreased from the pretreatment level to a mean level of 12+/-9.6 pg/mL in patients and 21+/-27 pg/mL in control subjects. Similar results were found with IL-6 concentration that decreased from the pretreatment level to a mean of 554+/-731 pg/mL in patients and 382 +/-568 pg/mL in control subjects. In conclusion, CVVH is associated with removal of substantial amounts of TNF and IL-6 from the circulation in traumatized critically ill patients, but the profile of these mediators is similar to that of controls, suggesting a nonclinically relevant elimination. Further prospective, randomized, clinical trials are needed to support our results.

Interferon-gamma in 388 immunocompromised and immunocompetent patients for diagnosing pleural tuberculosis.

The level of interferon-gamma (IFN-gamma) in pleural fluid has been reported to be increased in pleural tuberculosis. Nevertheless, its diagnostic value has not yet been well-established, and immunocompromised patients have not previously been evaluated. The aim of this study was to determine the value of the IFN-gamma level in pleural fluid for diagnosing tuberculous pleurisy in immunocompetent and immunocompromised patients. Three hundred and eighty eight consecutive patients were studied prospectively (73 with tuberculous pleural effusions, including nine with concurrent human immunodeficiency virus (HIV) infection and one after liver transplantation, and 315 with nontuberculous effusions). IFN-gamma was measured by radioimmunoassay. The sensitivity of the test, using a 3.7 U.mL-1 cut-off point, was 0.99 (95% confidence interval (95% CI) 0.93-1.00) and the specificity was 0.98 (95% CI 0.96-1.00). The sensitivity of the test did not differ in HIV-positive and HIV-negative patients. Patients with lymphoma, vasculitis or vascular connective tissue disease did not have abnormal IFN-gamma values. In conclusion, the level of interferon-gamma in pleural fluid is a very good diagnostic marker of tuberculous pleural effusion, even in immunocompromised patients.

Diagnostic value of CA 72-4, carcinoembryonic antigen, CA 15-3, and CA 19-9 assay in pleural fluid. A study of 207 patients.

BACKGROUND: The differential diagnosis of pleural effusion is a frequent clinical problem. Several tumor markers have been evaluated in pleural fluid, but the value of CA 72-4 assay and of combinations of tumor marker assays has not been firmly established. To find a minimally invasive tool for differentiating between pleural effusions of malignant or benign origin, the authors assessed the diagnostic value of CA 72-4, carcinoembryonic antigen (CEA), CA 15-3, and CA 19-9 assays in pleural fluid individually and in combination. METHODS: The authors prospectively studied 207 patients with pleural effusion (65 malignant, 48 tuberculous, 24 parapneumonic, 26 transudates, 14 miscellaneous, and 30 of unknown nonneoplastic origin). The levels of CA 72-4, CEA, CA 15-3, and CA 19-9 were measured in pleural fluid by radioimmunoassay. RESULTS: CA 72-4 assay in pleural fluid had an acceptable sensitivity and very good specificity for diagnosing malignant pleural effusion. The combination of CA 72-4 plus CEA plus CA 15-3 yielded the best accuracy, 0.90 (95% confidence interval [CI] 0.85-0.94), with a sensitivity of 0.78 (95% CI, 0.67-0.88), specificity of 0.95 (95% CI, 0.90-0.98), positive predictive value of 0.88 (95% CI, 0.77-0.95), and negative predictive value of 0.91 (range, 0.85-0.94). A good clinical strategy may be to begin with a CEA assay (specificity of I) and then, if it is negative, to add CA 15-3 or even CA 72-4 assays to improve sensitivity. The diagnosis of mesothelioma is more likely with a high CA 15-3 level and normal CEA and CA 19-9 levels. CONCLUSIONS: Assays of CEA, CA 72-4, and CA 15-3 in pleural fluid, or the combination of CEA with CA 15-3 and CA 72-4, was useful in differentiating between pleural effusion of malignant and benign origin.

Determination of tissue polypeptide-specific antigen in pleural fluid and serum from patients with pleural effusion.

As a tool for differentiating malignant and benign pleural effusions, we evaluated the diagnostic value of the assay of tissue polypeptide-specific antigen (TPS) in pleural fluid and serum, and of the pleural fluid TPS/serum TPS ratio in patients with pleural effusion. We studied prospectively 147 consecutive patients who had pleural effusions: 43 malignant pleural effusions and 104 benign pleural effusions. TPS levels were measured by RIA. The sensitivity and specificity of these measurements were: TPS in pleural fluid (cutoff 20,000 U/L): 0.21 and 0.98; TPS in serum (cutoff 300 U/L); 0.31 and 0.96; pleural fluid TPS/serum TPS ratio (cutoff 1200): 0.07 and 0.99. All these values enhanced the sensitivity of cytologic analysis of pleural fluid. However, we conclude that TPS assay in pleural fluid and serum, and the pleural fluid TPS/serum TPS ratio have limited diagnostic value in patients with pleural effusion.