Spontaneous bacterial peritonitis (SBP) is associated with an important production of inflammatory mediators. However, it is unknown whether there is a relationship between the abdominal production of these mediators and the development of renal impairment, one of the most important prognostic parameters in spontaneous bacterial peritonitis. We studied 52 cirrhotic patients at diagnosis and resolution of the infection, by measuring endotoxin, tumor necrosis factor (TNF), and interleukin-6 (IL-6) levels in plasma and ascitic fluid. Thirteen patients (25%) developed renal impairment. Patients developing renal impairment showed significantly higher plasma and ascitic fluid cytokine levels at diagnosis of infection than patients who did not (plasma TNF-α: 96.0 ± 38.7 vs. 39.1 ± 3.6 pg/mL, P = .0209; ascitic fluid TNF-α: 474.5 ± 118.1 vs. 160.8 ± 42.7 pg/mL, P = .0173; plasma IL-6: 6,635 ± 2,897 vs. 458 ± 109 pg/mL, P = .0004; ascitic fluid IL-6: 182,559 ± 47,328 vs. 39,250 ± 10,803 pg/mL, P = .0001). Independent predictors of development of renal impairment at diagnosis were: renal failure (blood urea nitrogen > 30 mg/dL or serum creatinine > 1.5 mg/dL) (P < .001), IL-6 levels in ascitic fluid (P < .001), and mean arterial pressure (P < .05). Ten of the 13 (77%) patients who developed renal impairment died during hospitalization, but only 2 of the 39 (5%) patients who did not (P= .0001). In addition, renal failure at diagnosis of the infection was the only independent predictor of hospital mortality (P < .001). In conclusion, the inflammatory response to the infection may be an important mechanism of renal impairment and the associated mortality in SBP.

The aim of our study was to analyse the serum interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interferon-γ(IFN-γ) levels in patients with AS and their relationship with disease activity. An ELISA test was used to analyse serum cytokine (IL-6, TNF-α, IL-1β and IFN-γ) levels in 69 patients with AS. Results were compared with those from 43 patients with RA and 36 patients with non-inflammatory back pain. The relationship between serum concentrations of the different cytokines and parameters of disease activity and severity in AS patients was also evaluated. IL-6 and TNF-α serum levels, but not IL-1β and IFN-γ, were significantly higher in AS than in NIBP. However, patients with RA showed higher serum levels of IL-6, TNF-α and IFN-γ than both AS and NIBP patients. In AS, IL-6 correlated with clinical parameters of disease activity with significant correlation being observed with laboratory parameters of inflammation such as ESR, CRP, platelet count and clinical parameters of severity such as vertebral mobility. TNF-α did not correlate with laboratory or clinical parameters of activity. Macrophagic cytokines (TNF-α and IL-6), are increased in AS patients and IL-6 closely correlated with the activity of the disease.

To evaluate the bronchial inflammatory response and its relationship to bacterial colonization in bronchiectasis, we performed a bronchoalveolar lavage (BAL) in 49 patients in stable clinical condition and in nine control subjects. BAL was processed for differential cell count, quantitative bacteriologic cultures, and measurement of inflammatory mediators. An increase was observed in the percentage of neutrophils (37 [0 to 98]) (median[range]) versus 1[0 to 4]%, p = 0.01), in the concentration of elastase (90.5 [8 to 2,930] versus 34 [9 to 44], p = 0.03), myeloperoxidase (9.1 [0 to 376] versus 0.3 [0.1 to 1.4], p = 0.01), and in the levels of TNF- α (4 [0 to 186] versus 0 [0 to 7], p = 0.03), IL-8 (195 [0 to 5,520] versus 3 [0 to 31], p = 0.001), and IL-6 (6 [0 to 115] versus 0 [0 to 3], p = 0.001) in patients with bronchiectasis compared with control subjects. Noncolonized patients showed a more intense bronchial inflammatory reaction than did control subjects. This inflammatory reaction was exaggerated in patients colonized by microorganisms with potential pathogenicity (MPP), with a clear relationship with the bronchial bacterial load. Patients with bronchiectasis showed a slight systemic inflammatory response, with poor correlations between systemic and bronchial inflammatory mediators, suggesting that the inflammatory process was mostly compartmentalized. We conclude that patients with bronchiectasis in a stable clinical condition present an active neutrophilic inflammation in the airways that is exaggerated by the presence of MPP, and the higher the bacterial load the more intense the inflammation.

BACKGROUND: Human epididymis protein 4 (HE4), a precursor of human epididymis protein, has been proposed as a tumor marker for ovarian cancer. We evaluated HE4 in comparison with cancer antigen 125 (CA 125) in healthy individuals and in patients with benign and malignant diseases. METHODS: CA 125 and HE4 serum concentrations were determined in 101 healthy individuals, 535 patients with benign pathologies (292 with benign gynecologic diseases) and 423 patients with malignant diseases (127 with ovarian cancers). CA 125 and HE4 cutoffs were 35 kU/L and 140 pmol/L, respectively. RESULTS: HE4 and CA 125 results were abnormal in 1.1% and 9.9% of healthy individuals and in 12.3% and 37% of patients with benign diseases, respectively. Renal failure was the most common cause of increased HE4 in patients with benign disease, who had significantly higher HE4 concentrations (P = 0.001) than patients with other benign diseases. HE4 showed a higher specificity than CA 125 in patients with benign gynecologic diseases, with abnormal concentrations in 1.3% and 33.2% of the patients, respectively. HE-4 concentrations were abnormal primarily in gynecologic cancer and lung cancer. By contrast, CA 125 was increased in many different nonovarian malignancies, including nonepithelial tumors. A significantly higher area under the ROC curve was obtained with HE4 than with CA 125 for differentiating benign from malignant diseases (0.755 vs 0.643) and in the differential diagnosis of gynecologic diseases (0.874 vs 0.722). CONCLUSIONS: HE4 has significantly higher diagnostic specificity than CA 125, and the combination of CA 125 and HE4 improved the detection of ovarian cancer in all stages and histological types.

Rationale: We have previously identified six serum tumor markers (TMs) (carcinoembryonic antigen, carbohydrate antigen 15.3, squamous cell carcinoma–associated antigen, cytokeratin-19 fragment, neuron-specific enolase, and pro–gastrin-releasing peptide) related to the presence of lung cancer (LC). Objectives: To validate their individual performance in an independent cohort, and to explore if their combined assessment (≥1 abnormal TM value) is a more accurate marker for LC presence. Methods: We determined these six TMs in 3,144 consecutive individuals referred to our institution by their primary care physician because of the clinical suspicion of LC. Measurements and Main Results: LC was excluded in 1,316 individuals and confirmed in 1,828 patients (1,563 with non–small cell LC and 265 with small cell LC). This study validated the previously reported performance of each individual TM. We also showed that their combined assessment (≥1 abnormal TM) had a better sensitivity, specificity, negative predictive value, and positive predictive value (88.5, 82, 83.7, and 87.3%, respectively) than each TM considered individually and that it increased the diagnostic performance (area under the curve) of a clinical model that included tumor size, age, and smoking status. In patients with radiographic nodules less than 3 cm, the negative predictive value of the TM panel was 71.8%, hence providing some support for a more conservative diagnostic approach. Finally we identified two TMs (neuron-specific enolase and pro–gastrin-releasing peptide) that differentiate the risk of non–small cell LC from that of small cell LC. Conclusions: The combined assessment of a panel of six serum TMs is a more accurate marker for LC presence than these same TMs considered individually. The potential of these TMs in the diagnostic and screening settings deserves further research.