Impact of endotoxin challenge in obese pigs.

Studies exploring the influence of obesity on septic shock remain limited and controversial. Pigs were chosen as a clinically relevant species, resembling to humans in various functions. We hypothesize obesity may impair porcine acute endotoxic shock. Four groups of five "Yucatan" minipigs were studied: lean and obese control groups, lean lipopolysaccharide (LPS) group receiving Escherichia coli endotoxin (LPS) and obese LPS group receiving the same endotoxin dose. We measured hemodynamic and oxygenation parameters, skin microvascular blood flow at rest and during reactive hyperemia, von Willebrand factor, tumor necrosis factor α, and interleukin 6. All measurements were performed at baseline and at 30, 60, 90, 150, and 300 min. Results were given as median with 25th to 75th interquartile range. Control groups remained stable during the study period. In LPS groups, administration of endotoxin resulted in a typical hypokinetic shock. In obese LPS group at 300 min, we observed a significant impairment of cardiac index (1.2 [1.06-1.45] vs. 1.7 [1.57-1.97] L/min per m, P = 0.008) compared with the lean LPS group; moreover, pulmonary hypertension (mean arterial pressure: 42 [39-47] vs. 32 [28-34] mmHg, P = 0.008), hypoxemia (partial pressure of oxygen: 216 [178-262] vs. 325 [285-414] mmHg, P = 0.02), and lactate levels (5.8 [4.2-6.8] vs. 3.9 [2.2-5.5] mmol/L, P = 0.04) were significantly higher compared with the lean LPS group. Throughout the study, rest flow and peak flow during reactive hyperemia were more decreased in the obese LPS group. Compared with the lean LPS group, tumor necrosis factor α levels at 60 min (269 [178-428] vs. 126 [105-166] ng/mL, P = 0.03) and interleukin 6 levels at 300 min (101 [61-142] vs. 52 [36-64] ng/mL, P = 0.03) were significantly higher in the obese LPS group. In our model of endotoxic shock, obese pigs developed a more severe hemodynamic failure with pronounced microcirculatory dysfunction and proinflammatory response.

Noninvasive diagnosis of large esophageal varices by Fibroscan: strong influence of the cirrhosis etiology.

BACKGROUND: Large esophageal varices (LOV) were diagnosed by endoscopy in patients with cirrhosis. Noninvasive method would be valuable. AIMS: To evaluate the diagnostic performance of Fibroscan for LOV prediction and to investigate the prognostic value of liver stiffness (LS) in cirrhosis. PATIENTS AND METHODS: One hundred and eighty-three patients with cirrhosis (103 alcohol, 58 viral, and 22 others) underwent an endoscopy and a Fibroscan. Of those patients, 41 (22.4%) had LOV. RESULTS: Median LS was 33.66 kPa (range: 12-75), higher in patients with LOV than those without (51.24 +/- 1.61 vs. 29.81 +/- 1.82 kPa, p < 0.0001), and in alcoholic than nonalcoholic (40.39 +/- 1.75 vs. 25.73 +/- 1.82, p < 0.0001). In whole population, a LS > or =48 kPa predicted LOV with sensitivity, specificity, positive, negative predictive values (PPV, NPV) of 73.2, 73.2, 44.1, and 90.4%, respectively, and an area under ROC curve (AUROC) of 0.75 (CI 95%: 0.69-0.82). For alcoholic cirrhosis, LS was > or =47.2 kPa with sensitivity, specificity, PPV, NPV of 84.6, 63.6, 44, and 92.5%, respectively, AUROC 0.77 (0.68-0.85). For viral cirrhosis, a LS > or =19.8 kPa generated diagnostic values of 88.9, 55.1, 26.7, and 96.4% and 0.73 (0.60-0.84). Sixteen (8.75%) patients died at 1 year. In multivariate analysis, LS was not predictive of mortality. CONCLUSIONS: Etiology of cirrhosis has strong impact on LS cutoff for diagnosis of LOV. Studies should be performed with homogenous cirrhosis etiology.