Oligo-glycerol based non-ionic amphiphilic nanocarriers for lipase mediated controlled drug release

A new class of non-ionic amphiphiles is synthesized using a diaryl derivative of diglycerol as a central core and functionalizing it with long alkyl chains (C-12/C-15) and monomethoxy PEG moiety (M_n: 350/550) by following a chemo-enzymatic approach. The aggregation behavior of the amphiphiles in aqueous medium is studied by using dynamic light scattering (DLS) and fluorescence spectroscopy, whereas the size and morphology of the aggregates are studied by transmission electron microscopy (TEM). A hydrophobic dye, Nile red and a hydrophobic drug, nimodipine, are used to demonstrate the nano-carrier capability of these non-ionic amphiphilic systems and the results are compared with amphiphilic analogues obtained from the triaryl derivatives of triglycerol. The in vitro controlled release of the encapsulated dye is successfully carried out in the presence of immobilized Candida antarctica lipase (Novozym 435). Furthermore, cytotoxicity data is also collected which suggests that the amphiphiles are suitable for biomedical applications.

A new series of oligo-glycerol based amphiphiles have been synthesized for drug delivery.     

Extracorporeal CO2 removal as bridge to lung transplantation in life‐threatening hypercapnia

In patients awaiting lung transplantation (LTX), adequate gas exchange may not be sufficiently achieved by mechanical ventilation alone if acute respiratory decompensation arises. We report on 20 patients with life‐threatening hypercapnia who received extracorporeal CO₂ removal (ECCO2‐R) by means of the interventional lung assist (ILA®, Novalung) as bridge to LTX. The most common underlying diagnoses were bronchiolitis obliterans syndrome, cystic fibrosis, and idiopathic pulmonary fibrosis, respectively. The type of ILA was pumpless arteriovenous or pump‐driven venovenous (ILA activve®, Novalung) in 10 patients each. ILA bridging was initiated in 15 invasively ventilated and five noninvasively ventilated patients, of whom one had to be intubated prior to LTX. Hypercapnia and acidosis were effectively corrected in all patients within the first 12 h of ILA therapy: PaCO₂ declined from 109 (70–146) to 57 (45–64) mmHg, P < 0.0001; pH increased from 7.20 (7.06–7.28) to 7.39 (7.35–7.49), P < 0.0001. Four patients were switched to extracorporeal membrane oxygenation due to progressive hypoxia or circulatory failure. Nineteen patients (95%) were successfully transplanted. Hospital and 1‐year survival was 75 and 72%, respectively. Bridging to LTX with ECCO2‐R delivered by arteriovenous pumpless or venovenous pump‐driven ILA is feasible and associated with high transplantation and survival rates.     

Prognostic Tools for Early Mortality in Hemorrhagic Stroke: Systematic Review and Meta-Analysis

Background and Purpose

Several risk scores have been developed to predict mortality in intracerebral hemorrhage (ICH). We aimed to systematically determine the performance of published prognostic tools.

Methods

We searched MEDLINE and EMBASE for prognostic models (published between 2004 and April 2014) used in predicting early mortality (<6 months) after ICH. We evaluated the discrimination performance of the tools through a random-effects meta-analysis of the area under the receiver operating characteristic curve (AUC) or c-statistic. We evaluated the following components of the study validity: study design, collection of prognostic variables, treatment pathways, and missing data.

Results

We identified 11 articles (involving 41,555 patients) reporting on the accuracy of 12 different tools for predicting mortality in ICH. Most studies were either retrospective or post-hoc analyses of prospectively collected data; all but one produced validation data. The Hemphill-ICH score had the largest number of validation cohorts (9 studies involving 3,819 patients) within our systematic review and showed good performance in 4 countries, with a pooled AUC of 0.80 [95% confidence interval (CI)=0.77-0.85]. We identified several modified versions of the Hemphill-ICH score, with the ICH-Grading Scale (GS) score appearing to be the most promising variant, with a pooled AUC across four studies of 0.87 (95% CI=0.84-0.90). Subgroup testing found statistically significant differences between the AUCs obtained in studies involving Hemphill-ICH and ICH-GS scores (p=0.01).

Conclusions

Our meta-analysis evaluated the performance of 12 ICH prognostic tools and found greater supporting evidence for 2 models (Hemphill-ICH and ICH-GS), with generally good performance overall.