Biomarcadores pronósticos de gravedad del dengue / Biomarkers for the prognosis of severe dengue

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Introduction: There are very few strategies for the early detection of the patients who might develop the severe form of the illness. Objective: To evaluate the utility of serum levels of some immune response mediators as early biomarkers for the severe dengue prognosis during the early phase of the illness. Materials and methods: Using a case-control design nested in a multicenter cohort from the AEDES network (a Colombian multicenter study), we compared TNF a, ST2, TRAIL and IDO levels in samples which were obtained during the early phase of the illness. Results: ST2, TRAIL and TNF a levels were higher in severe dengue patients compared with uncomplicated patients (p<0.0001), as follows: OR=24.8, CI95%= 6.1- 98.0; OR=18.0, CI95%= 4.6-69.1; OR=NC, CI95%= NC, respectively. We did not find statistically significant differences between IDO levels in severe dengue and uncomplicated dengue (p=1.000, OR=1.0, CI95%= 0.2-6.1). Conclusions: In the early phase of the dengue infection (96 hours), ST2, TRAIL and TNF a quantifications could contribute to the prediction of complications of the illness.

Study of serum osteoprotegrin [OPG], tumor necrosis factor-related apoptosis-inducing ligand [Trail] and fetuin-A in patients with chronic renal failure

Vascular and valvular calcifications are strong prognostic markers of cardiovascular disease mortality in chronic kidney disease [CKD] patients especially those on hemodialysis. It has been demonstrated that CKD patients with osteodystrophy have increased atherosclerosis and, more recently, increased coronary artery calcification. Was to evaluate the link between renal failure, atherosclerosis, vascular calcification and inflammation by determining the role of serum osteoprotegrin [OPG], tumor necrosis factor-related apoptosis-inducing ligand [TRAIL], and Fetuin A in the development of vascular calcification in patients with End stage renal failure disease [ESRD]. The study included, thirty patients on maintenance hemodialysis [HD] and fifteen patients with conservatively managed chronic renal failure [CRF] for whom dialysis was not performed. Both groups were compared to fifteen age and sex matched healthy individuals who constituted the control group. To all the subjects clinical examination, and 12 lead electro-cardiography were done. To all subjects the following investigations were performed: routine biochemical analysis, serum OPG, Fetuin A and plasma TRAIL Also serum parathyroid hormone [PTH], Calcium [total and ionized], phosphorus [Ph], and C- reactive protein [CRP] were measured. Finaly carotid ultra sonography of the pelvis and hand, and calculation of vascular calcification score were done. Carotid intima media thickness [CIMT] was found to be significantly higher in both undialyzed [CRF] patients and dialyzed [HD] patients when compared to controls [p<0.001 leach]. Also the difference between both groups of patients was statistically significant [p: 0.014]. Calcification score was found to be significantly higher in CRF and HD patients when compared to controls [p: 0.047 and < 0.001 respectively] Serum OPG level was significantly higher in both undialyzed CRF and dialyzed HD patients when compared to the control group [p: 0.041 and < 0.001 respectively].The level was also found to be significantly higher in the HD group when compared to CRF patients [p< 0.001]. Serum fetuin A level was found to be significantly lower in both CRF and HD patients when compared to the control group [p: 0.02, 0.05 respectively]. As regards TRAIL levels, no significant difference was found between the three studied groups. The level of the PTH was significantly higher in CRF undialyzed and HD patients when compared to control group [p: 0.021 and < 0.001 respectively]. CRP level was significantly higher in both patients groups when compared to controls [p< 0.001, 0.04 respectively].In the total patients group: there was a positive significant correlation between VC score and both PTH and AP. There was a positive significant correlation between OPG and [CIMT, Fetuin, AP and total Ca]. There was also a positive significant correlation between Fetuin A and both TRAIL and Albumin. By performing multiple logistic regression, only serum PTH was significant independent predictor of vascular calcification [p=0.006] and serum OPG was significant independent predictor of inflammation. [p=0.029]. The only parameter with significant ROC curve was PTH. It could be finally concluded that the increased level of OPG in CRF and HD patients might be a compensatory self defensive response against other factors that promote vascular calcification, or may possess potentially damaging properties, while the decreased level of Fetuin A reflects an inadequate response against the development of VC. Also the increase level of CRP denotes an ongoing inflammatory state and this causes down regulation of fetuin A which may represent the essential link between chronic inflammation and vascular calcification. PTH was found to be the best diagnostic marker of VC of all studied parameters, and was also the most independent predictor of VC, while OPG was the most independent predictor of inflammation