Procollagen type III aminoterminal propeptide as biomarker of host response in severe sepsis.

PURPOSE: The purpose of this study is to test the hypothesis that procollagen type III aminoterminal propeptide (PIIINP) is early elevated in septic episodes and can indicate the acute organ dysfunction/failure characterizing severe sepsis. MATERIALS AND METHODS: This prospective study included 107 consecutive septic patients (44 with sepsis, 13 with severe sepsis, and 50 with septic shock) and 45 controls. After blood sampling (within 48 hours after onset of septic episodes), serum was assayed. Patients were followed up, and their disease severity was daily evaluated. RESULTS: Procollagen type III aminoterminal propeptide (median [range]) increased in patients with sepsis (9.4 [2.2-42.4] ng/mL) compared with controls (3.6 [1.9-4.9] ng/mL; P<.001), exhibiting further significant increase in patients with severe sepsis and septic shock (19.5 [6.0-52.4] and 20.2 [1.8-89.2] ng/mL, respectively; P<.01-.001 vs sepsis). Among biomarkers of host response severity, PIIINP was the sole that was independently associated with severe sepsis/septic shock (P=.01). The area under the receiver operating characteristic curve for PIIINP to predict which patients with sepsis would eventually develop severe sepsis/septic shock was 0.87; the cutoff of 12 ng/mL had sensitivity 82% and specificity 89%. CONCLUSIONS: Increased serum PIIINP can signify severe sepsis/septic shock and predict which patients with sepsis will eventually develop severe sepsis/septic shock, thus representing a biomarker of risk stratification of patients with sepsis.

Insulin-like Growth Factor I and its binding protein 3 in sepsis.

OBJECTIVE: To investigate the Growth Hormone (GH)/Insulin-like Growth Factor-I (IGF-I) axis and identify the factors that determine IGF-I levels in adult septic patients of variable severity, i.e., with sepsis, severe sepsis or septic shock, in the acute phase of disease. DESIGN: In 107 consecutive septic patients (44 with sepsis, 13 with severe sepsis, and 50 with septic shock), GH, IGF-I, Insulin-like Growth Factor Binding Protein-3 (IGFBP-3), insulin, cortisol, albumin, thyroid hormones, C-reactive protein and interleukin-6 serum levels were measured once within 48 h after onset of a septic episode. Twenty-nine healthy volunteers served as controls. RESULTS: IGF-I and IGFBP-3 levels were decreased in patients with sepsis and severe sepsis (versus controls), decreasing further in patients with septic shock (versus sepsis). IGF-I levels were positively related to IGFBP-3, albumin, triiodothyronine and thyroxine, and inversely related to cortisol, sepsis severity, C-reactive protein, interleukin-6 and age. In multiple regression analysis, IGF-I levels were independently related to IGFBP-3 and albumin (lower in patients with decreased IGFBP-3 and albumin levels) (p<0.001 and p=0.01, respectively), and cortisol (lower in patients with increased cortisol levels) (p=0.04). IGFBP-3 accounted for most of the variance explained by the model (R(2)=0.519). GH levels were not related to IGF-I levels or mortality. IGF-I and IGFBP-3 levels were not associated with mortality. CONCLUSIONS: The GH/IGF-I axis is severely disrupted in septic patients. IGFBP-3 is the major determinant of IGF-I levels.

Markers of bone metabolism in eugonadal female patients with beta-thalassemia major.

Osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) have been recently implicated in the pathogenesis of various types of osteoporosis. The aim of this study was to investigate bone turnover in eugonadal female patients with this disease and characterize the possible role of the OPG/RANKL system in thalassemia-related bone loss. Markers of bone turnover and bone mineral density (BMD) were measured in 16 eugonadal young females with beta-thalassemia major and 18 age- and sex-matched healthy controls. Bone turnover was significantly increased in thalassemic patients compared to controls but OPG was significantly higher in healthy subjects. BMD values negatively correlated with urine markers of bone resorption but not with OPG/sRANKL system.