Serum vascular endothelial growth factor is associated with cardiovascular involvement and response to therapy in Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare histiocytosis, considered to be an inflammatory myeloid neoplasm. Tropism for specific involvements of the disease remains unexplained. Vascular endothelial growth factor-A (VEGF) is implicated in cancer pathophysiology and mutations of the RAS oncogene have been shown to induce upregulation of VEGF gene expression. We therefore hypothesized that VEGF might play a particular role in ECD pathophysiology. We conducted a retrospective, single-center study to assess serum VEGF (sVEGF) concentrations and determine whether they were associated with the characteristics of ECD patients, and to determine whether VEGF was expressed by histiocytes. We evaluated 247 ECD patients, 53.4% of whom had sVEGF levels above the normal range (>500 pg/mL). Patients with high sVEGF levels more frequently had cardiac and vascular involvement (58.3% vs. 41.4%, P=0.008 and 70.5% vs. 48.3%, P=0.0004, respectively). In treatment-naïve patients (n=135), the association of C-reactive protein >5 mg/L and sVEGF >500 pg/mL was strongly associated with vascular involvement (odds ratio=5.54 [95% confidence interval: 2.39-13.62], P<0.001), and independently associated with cardiac involvement (odds ratio=3.18 [95% confidence interval: 1.34-7.83], P=0.010) after adjustment for the presence of the BRAF V600E mutation. Changes in sVEGF concentration on treatment were associated with a response of cardiac involvement on consecutive cardiac magnetic resonance images. All histological samples analyzed (n=24) displayed histiocytes with intracytoplasmic expression of VEGF, which was moderate to high in more than 90% of cases. Our study suggests a role for VEGF in cardiac and vascular involvement in ECD.

Therapeutic Treatment Plan Optimization during the COVID-19 Pandemic: A Comprehensive Physicochemical Compatibility Study of Intensive Care Units Selected Drugs.

BACKGROUND: The SARS-CoV-2 pandemic has resulted in a dramatic rise of the demand for medical devices and drugs. In this context, an important shortage of programmable syringe pumps, used to administrate different drugs in intensive care units, was seen. The opportunity of administrating combinations of five intensive care units selected drugs (Sufentanil, Clonidine, Loxapine, Midazolam, and Ketamine) was considered. METHODS: The drug mixtures were studied in a pure form or diluted in NaCl 0.9% or G5%. Twenty-six possible combinations of the five drugs were produced in glass vials or polypropylene syringes and stored at 25 °C for 14 days. The LC method was implemented to study drugs combinations in the presence of the degradation products. The clearness and pH were also monitored. RESULTS: All the 26 possible combinations displayed adequate physicochemical stability at 25 °C: at least 3 days and 7 days, respectively, for the dilution in 0.9% NaCl or glucose 5%, and the pure drug products mixtures. CONCLUSIONS: The study provided sufficient stability results, covering the medication administration period of at least three days. The combination of more than two drugs offers the advantage of minimizing the individual doses and reduces unwanted side-effects. Hence, this study opens up the possibility of combining the five drugs in one single syringe, which is useful especially under the current circumstances associated with an important shortage of programmable syringe pumps and pharmaceuticals.

Management of diabetic foot ulcers: a 25% lidocaine topical cream formulation design, physicochemical and microbiological assessments.

Background: Given the importance of surgical debridement in healing of diabetic foot ulcers, effective local anaesthesia is required to manage the related extreme pain. The pharmaceutical proprietary products currently available have low concentrations and do not exceed 5% w/w local anaesthetic. Objective: Formulation design of a lidocaine cream of 25% and assessment of the intrinsic stability. Methods: A cream pharmaceutical form was chosen for its ability to cross the skin barrier and effectively anaesthetise the skin. The choice of cream formula is based on changes in the size of the emulsions and resistance to physical stress. Stability tests were assessed over a 6-month period in terms of physical (evaluation of oil droplets), microbiological (germ count and identification, and preservative antimicrobial efficacy) and chemical parameters (content and pH). Results: Under the study conditions, the drug product displayed good physicochemical and microbiological stability for 6 months at 20°C and 40°C, and no degradation product was detected. Due to the systemic adverse effects of lidocaine, the pH stability guarantee the drug product tolerance along with very weak systemic passage. Conclusions: Given the good physicochemical and microbiological stability of the drug product over 6-month period, it has been made available to the clinical unit. An average of 250 patients per year benefit from the treatment with an excellent efficacy/tolerability ratio.

[Preventing interruptions during the administration of medicines]. / Administration du médicament, prévenir les interruptions de tâches.

The medication use pathway is a complex process with a high risk of error, all the more so if it is interspersed with interruptions. Interruptions during care procedures are a real problem which can result in serious adverse events. A legal frame obliges the health institutions to secure the administration of medicines. This priority objective is translated by risks assessments, tools of self-assessment, audits, corrective actions, which allow a raising awareness of the professionals to the risks associated to medicines.