Injectable polyoxazoline grafted hyaluronic acid thermoresponsive hydrogels for biomedical applications.

Injectable thermosensitive hydrogels based on hyaluronic acid (HA) grafted with lower critical solution temperature (LCST) polyoxazoline (copolymers of poly(isopropyl-co-butyl oxazoline)) or P(iPrOx-co-BuOx) have been elaborated with tunable solution/gel temperature transitions and gel state elastic modulus. A suitable HA-g-P(iPrOx-co-BuOx-67/33)-0.10 sample with an iPrOx/BuOx ratio of 67/33, a polymerization degree (DP) of 25, a substitution degree (DS) of 10%, and displaying thermally induced gelling character with elastic (G') and viscous (G'') moduli crossover points at 25 °C and a G' at 37 °C around 80 Pa has been chosen for medical application. Hydrogels obtained with HA-g-P(iPrOx-co-BuOx-67/33)-0.10 exhibited high stability at 37 °C and excellent injectability properties with full and quick reversibility. The incorporation of a secondary network (HA), until 35 wt%, into the thermosensitive hydrogel also demonstrated very good stability and injectability.

Microgels Based on Carboxymethylpullulan Grafted with Ferulic Acid Obtained by Enzymatic Crosslinking in Emulsion for Drug Delivery Systems.

Carboxymethylpullulan (CMP) grafted with ferulic acid (FA) is crosslinked with laccase by the reverse water-in-oil emulsion technique (with sunflower oil) to obtain microgels with size from 40 to 200 µm. It is demonstrated that laccase activity and dispersion time have an impact on microgels' size. Fluorescence spectroscopy of different probes (e.g., pyrene, Nile red, and curcumin) shows the nonpolar characteristics of hydrophobic microdomains formed by the FA moieties and its dimers forming the crosslinking nodes. Encapsulation and release of curcumin or lidocaine used as drug models are studied in different buffers. Curcumin is well encapsulated but retained in microgels, while lidocaine is released at 65-70% in 2 h and 30 min in buffer simulating the gastrointestinal tract and at 75-85% in 1 h in acetate buffer pH 5.6 or phosphate-buffered saline (PBS) pH 6.9.

Evaluation of financial burden following complications after major surgery in France: Potential return after perioperative goal-directed therapy.

OBJECTIVE: Perioperative goal-directed therapy (PGDT) has been demonstrated to improve postoperative outcomes and reduce the length of hospital stays. The objective of our analysis was to evaluate the cost of complications, derived from French hospital payments, and calculate the potential cost savings and length of hospital stay reductions. METHODS: The billing of 2388 patients who underwent scheduled high-risk surgery (i.e. major abdominal, gynaecologic, urological, vascular, and orthopaedic interventions) over three years was retrospectively collected from three French hospitals (one public-teaching, one public, and one private hospital). A relationship between mortality, length of hospital stays, cost/patient, and severity scores, based mainly on postoperative complications but also on preoperative clinical status, were analysed. Statistical analysis was performed using Student's t-tests or Wilcoxon tests. RESULTS: Our analyses determined that a severity score of 3 or 4 was associated with complications in 90% of cases and this represented 36% of patients who, compared with those with a score of 1 or 2, were associated with significantly increased costs (€ 8205±3335 to € 22,081±16,090; P<0.001, delta of € 13,876) and a prolonged length of hospital stay (mean of 10 to 27 days; P<0.001, delta of 17 days). According to estimates for complications avoided by PGDT, there was a projected reduction in average healthcare costs of between € 854 and € 1458 per patient and a reduction in total hospital bed days from 1755 to 4423 over three years. Based on French National data (47,000 high risk surgeries per year), the potential financial savings ranged from € 40M to € 68M, not including the costs of PGDT and its implementation. CONCLUSION: Our analysis demonstrates that patients with complications are significantly more expensive to care for than those without complications. In our model, it was projected that implementing PGDT during high-risk surgery may significantly reduce healthcare costs and the length of hospital stays in France while probably improving patient access to care and reducing waiting times for procedures.