Background Beta-lactam antibiotics (βLA) are the most commonly used antibiotics in the intensive care unit (ICU). ICU patients present many pathophysiological features that cause pharmacokinetic (PK) and pharmacodynamic (PD) specificities, leading to the risk of underdosage. The French Society of Pharmacology and Therapeutics (SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (SFAR) have joined forces to provide guidelines on the optimization of beta-lactam treatment in ICU patients. Methods A consensus committee of 18 experts from the two societies had the mission of producing these guidelines. The entire process was conducted independently of any industry funding. A list of questions formulated according to the PICO model (Population, Intervention, Comparison, and Outcomes) was drawn-up by the experts. Then, two bibliographic experts analysed the literature published since January 2000 using predefined keywords according to PRISMA recommendations. The quality of the data identified from the literature was assessed using the GRADE® methodology. Due to the lack of powerful studies having used mortality as main judgement criteria, it was decided, before drafting the recommendations, to formulate only “optional” recommendations. Results After two rounds of rating and one amendment, a strong agreement was reached by the SFPT-SFAR guideline panel for 21 optional recommendations and a recapitulative algorithm for care covering four areas: (i) pharmacokinetic variability, (ii) PK-PD relationship, (iii) administration modalities, and (iv) therapeutic drug monitoring (TDM). The most important recommendations regarding βLA administration in ICU patients concerned (i) the consideration of the many sources of PK variability in this population; (ii) the definition of free plasma concentration between four and eight times the Minimal Inhibitory Concentration (MIC) of the causative bacteria for 100% of the dosing interval as PK-PD target to maximize bacteriological and clinical responses; (iii) the use of continuous or prolonged administration of βLA in the most severe patients, in case of high MIC bacteria and in case of lower respiratory tract infection to improve clinical cure; and (iv) the use of TDM to improve PK-PD target achievement. Conclusions The experts strongly suggest the use of personalized dosing, continuous or prolonged infusion and therapeutic drug monitoring when administering βLA in critically ill patients. Electronic supplementary material The online version of this article (10.1186/s13054-019-2378-9) contains supplementary material, which is available to authorized users.

Endothelial progenitor cells (EPCs) seem to be a promising option to treat patients with ischemic diseases. Here, we investigated the effects of late outgrowth EPCs, or endothelial colony-forming cells (ECFCs), a recently defined homogeneous subtype of EPCs, in a rat model of transient middle cerebral artery occlusion (MCAO). Either vehicle or 4.10(6) ECFCs, isolated from human cord blood, were intravenously injected 24 h after 1 h MCAO in rats assigned to control and transplanted groups respectively. (111)In-oxine-labeled ECFCs specifically homed to ischemic hemisphere and CM-Dil prelabeled ECFCs preferentially settled in the inner boundary of the core area of transplanted animals. Although incorporation of cells into neovessels was hardly detectable, ECFCs transplantation was associated with a reduction in apoptotic cell number, an increase in capillary density and a stimulation of neurogenesis at the site of injury. These effects were associated with an increase in growth factors expression in homogenates from ischemic area and may be related to the secretion by ECFCs of soluble factors that could affect apoptosis, vascular growth and neurogenesis. Microscopic examination of the ischemic hemisphere showed that ECFCs transplantation was also associated with a reduction in reactive astrogliosis. In conclusion, we demonstrated that ECFCs injected 24 h after MCAO settled in the injured area and improved functional recovery. The neurological benefits may be linked to a reduction in ischemia-induced apoptosis and a stimulation of ischemia-induced angiogenesis and neurogenesis. These findings raise perspectives for the use of ECFCs as a well-characterized cell therapy product for optimal therapeutic outcome after stroke.

Provided that the dose is adjusted for renal function, metformin treatment appears to be safe and still pharmacologically efficacious in moderate-to-severe CKD.

Aims Coronavirus disease 2019 (COVID‐19) is a rapidly progressing pandemic, with four million confirmed cases and 280,000 deaths at the time of writing. Some studies have suggested that diabetes is associated with a greater risk of developing severe forms of COVID‐19. The primary objective of the present study was to compare the clinical features and outcomes in hospitalized COVID‐19 patients with vs. without diabetes. Methods All consecutive adult patients admitted to Amiens University Hospital (Amiens, France) with confirmed COVID‐19 up until April 21 st , 2020, were included. The composite primary endpoint comprised admission to the intensive care unit (ICU) and death. Both components were also analyzed separately in a logistic regression analysis and a Cox proportional hazards model. Results A total of 433 patients (median age: 72; 238 (55%) men; diabetes: 115 (26.6%)) were included. Most of the deaths occurred in non‐ICU units and among older adults. Multivariate analyses showed that diabetes was associated neither with the primary endpoint (odds ratio (OR): 1.12; 95% confidence interval (CI): 0.66‐1.90) nor with mortality (hazard ratio: 0.73; 95%CI: 0.40‐1.34) but was associated with ICU admission (OR: 2.06; 95%CI 1.09‐3.92, p=0.027) and a longer length of hospital stay. Age was negatively associated with ICU admission and positively associated with death. Discussion Diabetes was prevalent in a quarter of the patients hospitalized with COVID‐19; it was associated with a greater risk of ICU admission but not with a significant elevation in mortality. Further investigation of the relationship between COVID‐19 severity and diabetes is warranted. This article is protected by copyright. All rights reserved.

LMP constitute a promising biomarker associated with plaque vulnerability in patients with high-grade carotid stenosis. These data provide clues for identifying asymptomatic subjects that are most at risk of neurologic events.