Combined measurements of N-terminal pro-brain natriuretic peptide and cardiac troponins in potential organ donors

Objective Brain death may induce cardiac dysfunction. In potential organ donors measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP) and circulating cardiac troponins T and I (cTnT and cTnI), alone or in combination, are performed to investigate the accuracy of these biomarkers for early diagnosis of left ventricular systolic dysfunction. Design and setting Prospective study in a multidisciplinary intensive care unit of an university hospital. Patients 63 brain-dead patients scheduled for multiple organ harvesting. Measurements and results We measured NT-proBNP, cTnT, and cTnI and determined fractional area change (FAC) using transesophageal echocardiography. Forty-five patients had normal FAC, 9 a moderate decrease in FAC (30–50), and 9 a severe decrease in FAC (≤ 30%). NT-proBNP and cTnT concentrations were significantly higher in patients with a severe decrease in FAC than in those with a moderate decrease. Combining measurements of these two biomarkers, the sensitivity of the test to predict severe decrease in FAC increased significantly to reach 1.00 compared with the sensitivities of individual measurements. The ROC curve area of combined measurements of NT-proBNP and cTnT was significantly higher than single measurements: 0.87 vs. 0.82 for NT-proBNP, 0.78 for cTnT, and 0.72 for cTnI. Conclusions In potential organ donors the combined measurement of NT-proBNP and cTnT concentrations is more accurate than individual measurement of NT-proBNP, cTnT, and cTnI in the early diagnosis of severe left ventricular systolic dysfunction. These findings may lead to improve the quality of cardiac care of the potential organ donors.     

The Effect of Dumping on Weight Loss in Conversion of Failed Restrictive Surgery: a Cross-Sectional Pilot Study

Purpose

Dumping is currently seen as a negative side effect of Roux-en-Y gastric bypass (RYGB). However, it may help patients to comply with their prescribed diet. In this study, we assess the role of dumping on weight loss in patients who have undergone conversion of failed restrictive surgery into RYGB.

Methods

An analysis was performed of 100 consecutive patients who underwent revisional RYGB (rRYGB) between 2006 and 2011 due to inadequate weight loss or band intolerance after laparoscopic adjustable gastric banding (LAGB). The percentage of excess weight loss (%EWL) was used to evaluate weight reduction. The Sigstad clinical diagnostic index was used to detect dumping symptoms.

Results

Fifty-five patients (59.1%) suffered from dumping. Overall, dumpers showed a greater %EWL than non-dumpers (83.8 ± 48.0 vs 66.9 ± 44.1%, respectively, p = 0.0725). When rRYGB was performed because of inadequate weight loss following LAGB, dumping played a crucial role in weight loss (88.0 ± 21.2 vs 68.9 ± 34.5%, p = 0.0137). This effect positively correlates to post-LAGB body mass index (BMI) with a statistically significant result at BMI >?35 kg/m² (82.4 ± 15.7 vs 58.4 ± 32.4%, p = 0.00341). A regression analysis of the Sigstad dumping score and %EWL shows that dumping tends to increase the %EWL.

Conclusions

This study provides new insights into the effect of dumping on weight loss in patients who underwent conversion of failed restrictive surgery into RYGB. Based on the findings in our patient group, we suggest that dumping helps patients achieve sustainable weight loss. Therefore, dumping can be regarded as a positive side effect rather than a complication.

     

Cost-effectiveness of activated protein C in real-life clinical practice

Background

Recombinant human activated protein C (rhAPC) has been reported to be cost-effective in severely ill septic patients in studies using data from a pivotal randomized trial. We evaluated the cost-effectiveness of rhAPC in patients with severe sepsis and multiple organ failure in real-life intensive care practice.

Methods

We conducted a prospective observational study involving adult patients recruited before and after licensure of rhAPC in France. Inclusion criteria were applied according to the label approved in Europe. The expected recruitment bias was controlled by building a sample of patients matched for propensity score. Complete hospitalization costs were quantified using a regression equation involving intensive care units variables. rhAPC acquisition costs were added, assuming that all costs associated with rhAPC were already included in the equation. Cost comparisons were conducted using the nonparametric bootstrap method. Cost-effectiveness quadrants and acceptability curves were used to assess uncertainty of the cost-effectiveness ratio.

Results

In the initial cohort (n = 1096), post-license patients were younger, had less co-morbid conditions and had failure of more organs than did pre-license patients (for all: P < 0.0001). In the matched sample (n = 840) the mean age was 62.4 ± 14.9 years, Simplified Acute Physiology Score II was 56.7 ± 18.5, and the number of organ failures was 3.20 ± 0.83. When rhAPC was used, 28-day mortality tended to be reduced (34.1% post-license versus 37.4% pre-license, P = 0.34), bleeding events were more frequent (21.7% versus 13.6%, P = 0.002) and hospital costs were higher (€47,870 versus €36,717, P < 0.05). The incremental cost-effectiveness ratios gained were as follows: €20,278 per life-year gained and €33,797 per quality-adjusted life-year gained. There was a 74.5% probability that rhAPC would be cost-effective if there were willingness to pay €50,000 per life-year gained. The probability was 64.3% if there were willingness to pay €50,000 per quality-adjusted life-year gained.

Conclusion

This study, conducted in matched patient populations, demonstrated that in real-life clinical practice the probability that rhAPC will be cost-effective if one is willing to pay €50,000 per life-year gained is 74.5%.     

Anti-citrullinated peptides antibodies in systemic sclerosis: Meta-analysis of frequency and meaning

Objectives

Diagnosis of systemic sclerosis (SSc) is partially determined by the presence of specific autoantibodies often associated with specific clinical features. Recent studies report the presence of ACPA in SSc. We aimed to evaluate the prevalence of ACPA in SSc and to assess their influence on clinical presentation of SSc.

Reduced encephalopathy in pigs with ischemia-induced acute hepatic failure treated with a bioartificial liver containing alginate-entrapped hepatocytes

OBJECTIVE: To analyze the effects of an extracorporeal bioartificial liver containing alginate bead-entrapped hepatocytes on pigs with ischemia-induced acute hepatic failure. DESIGN: Prospective animal study. SETTING: University and INSERM laboratory. SUBJECTS: Fifteen Large White/Pietrin female pigs weighing 20-30 kg. INTERVENTIONS: Acute hepatic failure was induced by end-to-side portocaval shunt and ligature of the whole porta hepatitis. The bioartificial liver was in a thermostabilized column, containing a fluidized bed of alginate beads that embedded porcine hepatocytes, connected to a plasmapheresis system. Intracranial pressure; survival; ammonia, total bilirubin, aminotransferases, alkaline phosphatase, and lactate concentrations; and clotting factors were studied. The groups were pigs with acute hepatic failure (group 1, n = 4), pigs with acute hepatic failure treated with bioartificial liver containing empty beads (group 2, n = 4), or porcine hepatocytes (group 3, n = 5). MEASUREMENTS AND MAIN RESULTS: In group 1, survival of pigs averaged 10.9 +/- 1.0 hrs; intracranial pressure reached 32.3 +/- 3.8 mm Hg and was associated with coma and cerebral edema. After connection to the bioartificial liver, the survival of acute hepatic failure pigs was 12.1 +/- 1.4 hrs in group 2 and 14.8 +/- 2.5 hrs in group 3. In group 3, intracranial pressure and bilirubin concentrations were reduced significantly compared with both group 1 and group 2. Neither signs of encephalopathy nor cerebral edema was observed in any animal of group 3. In all animals, plasma ammonium, aminotransferases, alkaline phosphatase, and lactate concentrations increased and clotting factors decreased with no significant differences between the three groups. Autopsy revealed a total necrosis of the liver, which was histologically confirmed. CONCLUSIONS: The ischemia-induced model of acute hepatic failure in pigs is reproducible and provides measurable clinical and biological features. A bioartificial liver containing alginate bead-entrapped hepatocytes improves the signs of encephalopathy in pigs with ischemia-induced acute hepatic failure, suggesting that the bioartificial liver can clear out toxic compounds that are released from necrotic livers.     

Imbalance between matrix metalloproteinases (MMP-9 and MMP-2) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in acute respiratory distress syndrome patients

OBJECTIVE: Matrix metalloproteinases (MMPs) are known to be involved in degradation of extracellular matrix. We aimed to assess the role of MMPs and their natural inhibitors (TIMPs) in the genesis and the evolution of acute respiratory distress syndrome (ARDS). DESIGN: Prospective, clinical study. SETTING: Intensive care unit of a university hospital. PATIENTS: Twenty-one patients were assigned to three different groups: Group 1 patients developed ARDS that rapidly resolved in <4 days; Group 2 patients developed ARDS lasting >8 days; Group 3 (control group) patients had clinical criteria for hospital-acquired pneumonia without ARDS. INTERVENTION: Bronchoalveolar lavages were performed on day 0 of the onset of ARDS and on days 4, 8, and 12 for unresolving ARDS. For group 3, the bronchoalveolar lavages were performed on day 0 of the pneumonia. On these bronchoalveolar lavage fluids, we measured the amount of MMP-9 and -2 and their inhibitors TIMP-1 and -2. MEASUREMENTS AND MAIN RESULTS: The amount of MMP-9 measured by enzyme-linked immunosorbent assay was significantly lower in the bronchoalveolar lavages from patients with ARDS (group 1 and group 2) compared with the control group (p <.01) throughout the study. The ratio MMP-9/TIMP-1 was also significantly smaller and was less than one in the two ARDS groups (p <.05) compared with the control group (group 3), where this ratio was greater than one. In the second bronchoalveolar lavages, this ratio was greater than one only in the ARDS group that rapidly resolved (group 1), whereas it stayed less than one when the ARDS was lasting (group 2). Concerning the quantity of MMP-2 and the ratio MMP-2/TIMP-2, there was no statistical difference between the three groups throughout the study. Using zymography, there was no significant difference in the amounts of active and latent MMP-9 between the three groups. Moreover, no significant difference in the quantity of latent and active MMP-2 in the three groups was noted. CONCLUSION: These results suggest that the MMP-9 level and MMP-9/TIMP-1 ratio play a role in the pathogenesis of ARDS and, namely, the imbalance between MMP-9 and TIMP-1 would participate in airway remodeling leading to either short- or long-course ARDS. The ratio MMP-9/TIMP-1 could be a predictive factor of the ARDS evolution.     

MR imaging,targeting and characterization of pulmonary fibrosis using intra‐tracheal administration of gadolinium‐based nanoparticles

Idiopathic pulmonary fibrosis is a devastating disease. Animal models are critical to develop new diagnostic approaches. We investigate here whether the application of an ultra‐short echo time MRI sequence combined with the intra‐tracheal administration of Gd‐based nanoparticles can help to visualize and characterize pulmonary fibrosis in mice. 21 mice were imaged. Treated mice were administered bleomycin. MRI was used for longitudinal detection of bleomycin‐induced lung injury from Day 1 up to Day 60. On Day 30, all mice received nanoparticles and MR images were acquired. A signal enhancement of 120% and 50% in fibrotic lesions and healthy tissues respectively was obtained. A twofold increase of contrast‐to‐noise ratio between fibrotic and healthy tissue was also observed, leading to a more accurate delineation of the extent of fibrosis. The elimination time constant of the nanoparticles was 54% higher in fibrotic lesions. Bleomycin‐induced lung injury can be monitored using MRI. Intra‐tracheal administration of Gd‐based nanoparticles enabled us to enhance fibrotic tissue in lungs but also to extract imaging biomarkers that quantify elimination and diffusion of contrast agents and can characterize fibrotic tissue. The added value of MRI associated with pulmonary administration of contrast agents is key to better understand the lung fibrotic process and monitor drug response in pre‐clinical studies, which will be valuable for translational applications. Copyright © 2016 John Wiley & Sons, Ltd.     

Process induced transformations during tablet manufacturing: phase transition analysis of caffeine using DSC and low frequency micro-Raman spectroscopy

The phase transition of a model API, caffeine Form I, was studied during tableting process monitored with an instrumented press. The formulation used had a plastic flow behavior according to the Heckel model in the compression pressure range of 70-170 MPa. The quantitative methods of analysis used were Differential Scanning Calorimetry (DSC) and low frequency Micro Raman Spectroscopy (MRS) which was used for the first time for the mapping of polymorphs in tablets. They brought complementary contributions since MRS is a microscopic spectral analysis with a spatial resolution of 5 μm³ and DSC takes into account a macroscopic fraction (10 mg) of the tablet. Phase transitions were present at the surfaces, borders and center of the tablets. Whatever the pressure applied during the compression process, the transition degree of caffeine Form I toward Form II was almost constant. MRS provided higher transition degrees (50-60%) than DSC (20-35%). MRS revealed that caffeine Form I particles were partially transformed in all parts of the tablets at a microscopic scale. Moreover, tablet surfaces showed local higher transition degree compared to the other parts.