Ventilator-associated pneumonia in trauma patients is associated with lower mortality: results from EU-VAP study.

BACKGROUND: Differences in trauma patients developing ventilator-associated pneumonia (VAP) are described regarding etiology and risk factors associated. We aim to describe the differences in outcomes in trauma and nontrauma patients with VAP. METHODS: A prospective, observational study conducted in 27 intensive care units from nine European countries. We included patients requiring invasive mechanical ventilation for >48 hours who developed VAP. Logistic regression model was used to assess the factors independently associated with mortality in trauma patients with VAP. RESULTS: A total of 2,436 patients were evaluated; 465 developed VAP and of these 128 (27.5%) were trauma patients. Trauma patients were younger than nontrauma (45.3 ± 19.4 vs. 61.1 ± 16.7, p < 0.0001). Nontrauma had higher simplified acute physiology score II compared with trauma patients (45.5 ± 16.3 vs. 41.1 ± 15.2, p = 0.009). Most prevalent pathogens in trauma patients with early VAP were Enterobacteriaceae spp. (46.9% vs. 27.8%, p = 0.06) followed by methicillin-susceptible Staphylococcus aureus (30.6% vs. 13%, p = 0.03) and then Haemophilus influenzae (14.3% vs. 1.9%, p = 0.02), and the most prevalent pathogen in late VAP was Acinetobacter baumannii (12.2% vs. 44.4%, p < 0.0001). Mortality was higher in nontrauma patients than in trauma patients (42.6% vs. 17.2%, p < 0.001, odds ratio [OR] = 3.55, 95%CI = 2.14-5.88). A logistic regression model adjusted for sex, age, severity of illness at intensive care unit admission, and sepsis-related organ failure assessment score at the day of VAP diagnosis confirmed that trauma was associated with a lower mortality compared with nontrauma patients (odds ratio [OR] = 0.37, 95%CI = 0.21-0.65). CONCLUSIONS: Trauma patients developing VAP had different demographic characteristics and episodes of etiology. After adjustment for potential confounders, VAP episodes in trauma patients are associated with lower mortality when compared with nontrauma patients.

Variable region heavy chain glycosylation determines the anticoagulant activity of a factor VIII antibody.

BACKGROUND: N-glycosylation occurs in the variable region of about 10% of antibodies but the role of carbohydrate at this location is still poorly understood. OBJECTIVES: We investigated the function of N-glycosylation in the variable region of the heavy chain of a human monoclonal antibody, mAb-LE2E9, that partially inhibits factor VIII (FVIII) activity during coagulation. METHODS AND RESULTS: Enzymatic deglycosylation indicated that the oligosaccharides do not determine the affinity of the antibody but enhance its FVIII neutralizing activity. A mutant antibody lacking the N-glycosylation site in the variable region of the heavy chain inhibited FVIII activity by up to 40%, while inhibition by the native antibody was 80%. To evaluate the physiological effect of such a FVIII inhibition, we investigated the ability of the mutant antibody devoid of N-glycosylation in the variable region to prevent thrombosis in mice with a strong prothombotic phenotype resulting from a type II deficiency mutation in the heparin binding site of antithrombin. Despite its moderate inhibition of FVIII activity, the mutant antibody significantly prevented thrombosis in treated animals. We also carried out glycan analysis of native and mutant antibodies. CONCLUSIONS: Modification of glycosylation in the variable region of antibodies contributes to the diversity of FVIII type II inhibition possibly by steric hindrance of the active site of FVIII by glycans, and may provide a novel strategy to modulate the functional activity of therapeutic antibodies.

Current surgical management of acute pancreatitis.

BACKGROUND: About 20% of the patients with acute pancreatitis may run a rapidly progressive or fulminant course resulting in the multiple organ dysfunction syndrome with or without accompanying sepsis. In this subset of patients, the mortality rate still ranges from less than 10% with sterile to over 30% with infected pancreatic necrosis. The goal of this review is to assess the available treatment strategies to allow the development of a formalized surgical approach to those patients. METHODS: A literature review of management of acute pancreatitis. RESULTS AND CONCLUSION: Over the past 20 years, there has been a substantial change in the surgical management of severe acute pancreatitis. This change has been away from a preventive surgery based on early major interventions towards a surgery of complications based increasingly on less aggressive options that take place at a later stage of the attack with specific criteria governing the timing of surgical therapy. Non-surgical options remain more than ever the cornerstone of management in many of these patients.

Elucidation of the binding regions of PAI-1 neutralizing antibodies using chimeric variants of human and rat PAI-1.

Increased levels of plasminogen activator inhibitor-1 (PAI-1), the main physiological inhibitor of tissue-type plasminogen activator (t-PA) in plasma, are a known risk factor for thromboembolic and cardiovascular diseases. The elucidation of the binding site of inhibitory monoclonal antibodies may contribute to the rational design of PAI-1 modulating therapeutics. In this study, homolog-scanning mutagenesis was used to identify the binding region of a variety of human PAI-1 inhibitory antibodies, lacking cross-reactivity with rat PAI-1. Therefore. eight chimeric human/rat PAI-1 variants, containing rat PAI-1 substitutions at the N-terminal or C-terminal end with splicing sites at positions 26, 81, 187, 277 or 327, were generated and purified. Biochemical characterization revealed that all chimeras were folded properly. Subsequently, surface plasmon resonance was used to determine the affinity of various monoclonal antibodies for these chimera. Comparative analysis of the affinity and ELISA data allowed the identification of the major binding region of the inhibitory antibodies MA-8H9D4, MA-33B8F7, MA-44E4, MA-42A2F6 and MA-56A7C10. Thus, three segments in human PAI-1 containing each at least one site involved in the neutralization of PAI-1 activity could be identified, i.e. (1) the segment from residue 81 to residue 187 (comprising alpha-helices hD, hE and hF, beta-strands s4C, s3A, s2A and s1A and the loops connecting these elements). (2) the segment between residues 277 and 327 (hI, thIs5A, s5A and s6A) and (3) the region C-terminal from amino acid 327, including the reactive site loop. The current data. together with previous data, indicate that PAI-1 contains at least four different regions that could be considered as putative targets to modulate its activity.

The timing of epiphysiodesis. A comparative study between the use of the method of Anderson and Green and the Moseley chart.

This retrospective study compares two groups of patients who underwent an epiphysiodesis for leg length discrepancy. In group A (47 patients) the timing of the epiphysiodesis was calculated using the method of Anderson and Green; in group B (36 patients) the Moseley chart was used. A leg length discrepancy of 1.5 cm or less at maturity was considered a satisfactory result. Group A showed 51% good results, group B 63.9%. In both groups, an important source of the poor results was error in calculation and prediction: 30.4% in group A (or 15% of the total), 61.5% in group B (or 22% of the total). The percentage of patients presenting too late was also considerable and accounted for 34.8% of the poor results in group A and for 23.1% in group B. The unpredictability of growth rate is a lesser problem in group B (15.4% of the poor results) than in group A (30.4%). If the uncontrollable causes of poor results are omitted, only 18% of the poor results in the total group of patients could be accounted for by miscalculation.

[Renewal of pulmonary insoluble collagen in the adult rat]. / Renouvellement du collagène pulmonaire insoluble chez le rat adulte.

Study of polymeric pulmonary collagen in adult Rats showed that about 70% of collagen was renewed with a half-time equal to 525 days. This value is to be compared with the median life-span of this rat strain, 890 days. The remaining 30% of polymeric collagen is renewed with a shorter half time, about 30 days.