Dimitrios Tzivras

Changes in Adaptive and Innate Immunity in Patients with Acute Pancreatitis and Systemic Inflammatory Response Syndrome

Background: Acute pancreatitis is a form of inflammation with clinical features ranging from pancreatic inflammation to fatal systemic manifestations. The aim of this study was to clarify changes in lymphocyte subsets and alterations in the functioning of natural killer (NK) cells. Patients and Methods: Forty-five patients were enrolled into the study; 35 with acute pancreatitis and systemic inflammatory response syndrome (SIRS) and 10 healthy subjects. Blood was sampled early from all patients. Blood immune cells were studied on days 1 and 4 by flow cytometry. Tumor necrosis factor-α (TNFα) and interleukin (IL)-6 were estimated from supernatants of NK cells before/after stimulation with lipopolysaccharide (LPS). Results: Apoptosis in patients was significantly different on days 1 and 4 compared with controls. Apoptosis of CD4(+) lymphocytes was significantly correlated with the days to resolution of SIRS (r = +0.586, p = 0.022). Significant differences were observed in TNFα and IL-6 on day 1 with/without LPS stimulation between patients and healthy individuals. Significantly increased levels of TNFα and IL-6 were found after LPS stimulation compared with unstimulated supernatants in day 1. Conclusion: NK cells altered their secretory status when stimulated with LPS. This finding could be explained by the cellular reprogramming of NK cells in the field of acute pancreatitis and SIRS.

Comparison of Fibrate, Ezetimibe, Low- and High-Dose Statin Therapy for the Dyslipidemia of the Metabolic Syndrome in a Mouse Model

Background and Aim: The treatment-of-choice for the optimal management of the dyslipidemia of the metabolic syndrome (MetS) is not clearly defined. We compared the efficacy of 4 drug regimes for the management of this dyslipidemia in a mouse model. Materials and Methods: A total of 60 C57Bl6 mice comprised the study group. The first 10 received standard mouse food for the whole experiment (control group). The remaining 50 mice received atherogenic diet for 14 weeks until the development of the MetS. The mice were then divided into 5 groups: the 1st group continued receiving atherogenic diet, while the other 4 groups received atherogenic diet plus ezetimibe (10 mg/kg per day), fenofibrate (100 mg/kg per day), low-dose atorvastatin (10 mg/kg per day), or high-dose (40 mg/kg per day) atorvastatin, respectively, for another 8 weeks. Results: High-dose atorvastatin treatment achieved the best lipid profile compared with low-dose atorvastatin, ezetimibe, and fibrate therapy. The lipid profile of mice receiving atherogenic diet plus high-dose atorvastatin treatment was similar with mice on regular chow. Conclusions: High-dose atorvastatin treatment resulted in optimization of the lipid profile in the presence of a high-fat atherogenic diet in a mouse model. Our results suggest that high-dose atorvastatin treatment may be the optimal treatment option for the dyslipidemia associated with MetS. Nevertheless, verification of these results in humans is required before any definite conclusions can be drawn.

Factors Influencing Survival in Stage IV Colorectal Cancer: The Influence of DNA Ploidy

Objective. To evaluate the prognostic significance of microscopically assessed DNA ploidy and other clinical and laboratory parameters in stage IV colorectal cancer (CRC). Methods. 541 patients with histologically proven stage IV CRC treated with palliative chemotherapy at our institution were included in this retrospective analysis, and 9 variables (gender, age, performance status, carcinoembryonic antigen, cancer antigen 19-9, C-Reactive Protein (CRP), anaemia, hypoalbuminaemia, and ploidy (DNA Index)) were assessed for their potential relationship to survival. Results. Mean survival time was 12.8 months (95% confidence interval (CI) 12.0–13.5). Multivariate analysis revealed that DNA indexes of 2.2–3.6 and >3.6 were associated with 2.94 and 4.98 times higher probability of death, respectively, compared to DNA index <2.2. CRP levels of >15 mg/dL and 5–15 mg/dL were associated with 2.52 and 1.72 times higher risk of death, respectively. Hazard ratios ranged from 1.29 in patients mild anaemia (Hb 12–13.5 g/dL) to 1.88 in patients with severe anaemia (Hb < 8.5 g/dL). Similarly, the presence of hypoalbuminaemia (albumin < 5 g/dL) was found to confer 1.41 times inferior survival capability. Conclusions. Our findings suggest that patients with stage IV CRC with low ploidy score and CRP levels, absent or mild anaemia, and normal albumin levels might derive greatest benefit from palliative chemotherapy.

Pilot Study of Adalimumab for Early Prevention and/or Treatment of Post-Operative Endoscopic Recurrence of Crohn's Disease

index (HBI) and serum C-reactive protein (CRP)] at baseline, before each IFX infusion, and 12 weeks after therapy, and on the degree of mucosal healing (MH) at weeks 12-20 after IFX compared to endoscopy just before initiation of IFX. Complete responders had normal HBI scores, CRP levels and complete MH; partal responders had a >50% drop in HBI scores and CRP levels and residual ulcers and/or cobblestone despite improvement over baseline; and, primary non responders showed no change or worsened HBI scores, CRP levels and endoscopy. Serum samples were obtained at baseline and at 12 weeks and were subjected to proteomic analysis, i.e. two-Dimensional Gel Electrophoresis (2DE), coupled with MatrixAssisted Laser Desorption/ Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS). Selected proteins were further evaluated by Western blotting. Results: Serum proteomic analysis was performed in 6 complete, 6 partial and 6 primary non responders to IFX. Administration of IFX markedly changed the serum protein profile of CD patients. Despite the small number of individuals tested, we obtain results suggesting that proteomic markers may help to understand response to IFX and possibly try to define new markers for response prediction. Although a confirmation study should now be done on a larger cohort of independent patients, several proteins were found to be significantly overexpressed in partial and primary non responders versus complete responders were: APOΑ1, APOA4, Alpha-1antitrypsin, beta-2-glycoprotein, clusterin, C1R, C3, C4, fibrinogen, prothrombin, transthyretin and VTDB. Conclusion: Proteomics-based approaches are useful tools for providing global disease information and identifying biomarkers in complex diseases such as CD. This is the first proteomic study on response to IFX in a Greek CD cohort. Validation studies on a much larger cohort of patients are currently in progress.