Increase of circulating endocan over sepsis follow-up is associated with progression into organ dysfunction.

How circulating inflammatory mediators change upon sepsis progression has not been studied. We studied the follow-up changes of circulating vasoactive peptides and cytokines until the improvement or the worsening of a patient and progression into specific organ dysfunctions. In a prospective study, concentrations of tumor necrosis factor-alpha (TNFα), interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFNγ), endocan and angiopoietin-2 (Ang-2) were measured in serum by an enzyme immunoassay in 175 patients at baseline; this was repeated within 24 h upon progression into new organ dysfunction (n = 141) or improvement (n = 34). Endocan and Ang-2 were the only parameters that were significantly increased among patients who worsened. Any increase of endocan was associated with worsening with odds ratio 16.65 (p < 0.0001). This increase was independently associated with progression into acute respiratory distress syndrome (ARDS) as shown after logistic regression analysis (odds ratio 2.91, p: 0.002). Changes of circulating cytokines do not mediate worsening of the critically ill patients. Instead endocan and Ang2 are increased and this may be interpreted as a key-playing role in the pathogenesis of ARDS and septic shock. Any increase of endocan is a surrogate of worsening of the clinical course.

Experimental isolation and transplantation of hepatocytes with the use of antibody against interleukin-2 receptor (daclizumab) as immunosuppressive agent.

INTRODUCTION: Daclizumab (Dmab) is a genetically engineered humanized IgG1 monoclonal antibody that binds to the alpha chain of the interleukin-2 receptor (Tac, CD25, p55) expressed on activated human T lymphocytes. Dmab has been used in a clinical protocol of islet transplantation with satisfactory results. The aim of the present study was to evaluate the use of an antibody against the interleukin-2 receptor (Dmab) as an immunosuppressive agent in an experimental model of hepatocyte allotransplantation (allo-Tx) in rats with fulminant hepatic failure (FHF). MATERIALS AND METHODS: Six Wistar rats were used as donors and 48 Lewis rats as recipients: four groups of 12 animals each with induction of FHF and 24 hour later hepatocyte Tx--group A: no treatment; group B: cyclosporin (20 mg/kg days 0 to 5 and 10 mg/kg days 6 to 15); group C: Dmab (0.05 mg day of Tx and 0.05 mg day 7); and group D: Dmab and cyclosporine. Hepatocytes were transplanted intrasplenically. Animals were followed for 15 days. RESULTS: Statistical analysis showed better survival among groups C (83%, MST = 13) and D (92%, MST = 14.25) compared to groups A (max 72, MST = 1.5) or B (50%, MST = 9). Survival in group D was better but not significantly than group C. Biochemical evaluation and histology confirmed satisfactory function and engraftment, respectively. CONCLUSION: This experimental model showed the safe, effective use of Dmab.

Use of mycophenolate mofetil in the experimental allo-transplantation of hepatocytes in rats with fulminant hepatic failure.

AIM: The aim of the study was to evaluate the beneficial effect of mycophenolate mofetil (MMF) as an immunosuppressive agent for experimental transplantation of hepatocytes in rats with fulminant hepatic failure (FHF). MATERIALS AND METHODS: Six Wistar rats were used as donors and 40 Lewis rats at recipients, including four groups of 10 animals each. Group A received no treatment; Group B, cyclosporine (20 mg/kg days 0-5 and 10 mg/kg days 6-15); Group C, MMF (12 mg/kg per os every day); and Group D, MMF (23 mg/kg per os every day). Hepatocytes were transplanted intrasplenically. Animals were followed for 15 days. RESULTS: The survival rates for Group A were maximum 72 h, whereas Groups B, C, and D showed 50%, 70%, and 80%, respectively. Biochemical evaluation and histology showed satisfactory function and engraftment, respectively. CONCLUSION: The use of MMF in this experimental model yielded safe, satisfactory immunosuppression especially at the dose of 23 mg/kg.

Changes in thenar muscle tissue oxygen saturation assessed by near-infrared spectroscopy during weaning from mechanical ventilation.

BACKGROUND: Tissue oxygen saturation (StO2) measured by near-infrared spectroscopy (NIRS) has been used to provide information on local tissue oxygenation in different clinical settings. This study aims to determine the effect of weaning from mechanical ventilation on thenar muscle StO2. METHODS: In consecutive critically ill mechanically ventilated patients, StO2 at the thenar eminence, along with a vascular occlusion test (VOT), were measured by NIRS, on mechanical ventilation and during a 2-hour T-piece spontaneous breathing trial (SBT). Hemodynamic, gas exchange and respiratory variables were recorded. RESULTS: Forty-four patients were included in this study, 25 tolerated the SBT and 19 failed. On mechanical ventilation, no differences in any measured variable were observed between patients who succeeded or failed. Two minutes after SBT start, StO2 was decreased in patients who failed whereas it did not change in patients who succeeded (P<0.001). For all data, 2 minutes after the start of SBT, StO2 significantly correlated with SaO2 (r=0.32, P=0.037) and with the respiratory frequency/tidal volume (f/VT) index (r=-0.34, P=0.023). VOT-derived StO2 downslope and StO2 upslope did not change significantly along the SBT test. The maximum StO2 value, its ratio to minimum StO2, and the post-VOT StO2 value decreased significantly in patients who failed whereas no change was found in those who succeeded the SBT (P=0.003, P=0.025 and P<0.001 respectively). StO2 and f/VT at the second minute of SBT yielded a receiver operator characteristics curve area value of 0.77 and 0.80, P=0.002, respectively, in detecting the SBT outcome. CONCLUSION: SBT failure was associated with a significant impairment of thenar muscle StO2. A decrease of StO2 at 2 minutes after disconnection from the ventilator was associated with SBT failure. Further validation is warranted.