Local anaesthetic dosage of peripheral nerve blocks in children: analysis of 40 121 blocks from the Pediatric Regional Anesthesia Network database

Background

The knowledge regarding appropriate dosage of local anaesthetics for peripheral nerve blocks in children is very scarce. The main objective of the current investigation was to evaluate dosing patterns of local anaesthetics in children receiving peripheral nerve blocks across multiple paediatric hospitals in the USA. We also sought to estimate the incidence of local anaesthetic systemic toxicity.

Inflammatory biomarkers in infective endocarditis: machine learning to predict mortality

Infective endocarditis (IE) is the cardiac disease with the highest rates of mortality. New biomarkers that are able to identify patients at risk for death are required to improve patient management and outcome. This study aims to investigate if cytokines, chemokines and growth factors measured at IE diagnosis can predict mortality. Patients with definite IE, according to the Duke’s modified criteria, were included. Using high-performance Luminex assay, 27 different cytokines, chemokines and growth factors were analyzed. Machine learning techniques were used for the prediction of death and subsequently creating a decision tree, in which the cytokines, chemokines and growth factors were analyzed together with C-reactive protein (CRP). Sixty-nine patients were included, 41 (59%) male, median age 54 [interquartile range (IQR) = 41–65 years] and median time between onset of the symptoms and diagnosis was 12 days (IQR = 5–30 days). The in-hospital mortality was 26% (n = 18). Proinflammatory cytokines interkeukin (IL)-15 and C-C motif chemokine ligand (CCL4) were found to predict death, adding value to CRP levels. The decision tree predicted correctly the outcome of 91% of the patients at hospital admission. The high-risk group, defined as CRP ≥ 72 mg/dL, IL-15 ≥ 5·6 fg/ml and CCL4 ≥ 6·35 fg/ml had an 88% in-hospital mortality rate, whereas the patients classified as low-risk had a mortality rate of 8% (P = < 0·001). Cytokines IL-15 and CCL4 were predictors of mortality in IE, adding prognostic value beyond that provided by CRP levels. Assessment of cytokines has potential value for clinical risk stratification and monitoring in IE patients.     

Creatine supplementation impairs airway inflammation in an experimental model of asthma involving P2 × 7 receptor

Creatine (Cr) is a substrate for adenosine triphosphate synthesis, and it is the most used dietary supplement among professional and recreative athletes and sportsmen. Creatine supplementation may increase allergic airway response, but the cellular and molecular mechanisms are unknown. We used murine model of OVA‐induced chronic asthma and showed that Cr supplementation increased total proteins, ATP level, lymphocytes, macrophages, and IL‐5 levels in BALF, as well as IL‐5 in the supernatant of re‐stimulated mediastinal lymph nodes. IL‐5 and IL‐13 expression by epithelial cells and by peribronchial leukocytes were increased by Cr. Cr augmented the expression of P2 × 7 receptor by peribronchial leukocytes and by epithelial cells, and increased the accumulation of eosinophils in peribronchial space and of collagen fibers in airway wall. In human cells, while Cr induced a release of ATP, IL‐6, and IL‐8 from BEAS‐2B cells, whole blood cells, such as eosinophils, and CD4⁺ T cells, P2 × 7 receptor inhibitor (A740003) reduced such effects, as denoted by reduced levels of ATP, IL‐6, and IL‐8. Therefore, Cr supplementation worsened asthma pathology due to activation of airway epithelial cells and peribronchial leukocytes, involving purinergic signaling.     

CXCR2 is critical for bacterial control and development of joint damage and pain in Staphylococcus aureus‐induced septic arthritis in mouse

Staphylococcus aureus is the main pathogen associated with septic arthritis. Upon infection, neutrophils are quickly recruited to the joint by different chemoattractants, especially CXCR1/2 binding chemokines. Although their excessive accumulation is associated with intense pain and permanent articular damage, neutrophils have an important function in controlling bacterial burden. This work aimed to study the role of CXCR2 in the control of infection, hypernociception and tissue damage in S. aureus‐induced septic arthritis in mice. The kinetics of neutrophil recruitment correlated with the bacterial load recovered from inflamed joint after intra‐articular injection of S. aureus. Treatment of mice from the start of infection with the non‐competitive antagonist of CXCR1/2, DF2156A, reduced neutrophil accumulation, cytokine production in the tissue, joint hypernociception and articular damage. However, early DF2156A treatment increased the bacterial load locally. CXCR2 was important for neutrophil activation and clearance of bacteria in vitro and in vivo. Start of treatment with DF2156A 3 days after infection prevented increase in bacterial load and reduced the hypernociception in the following days, but did not improve tissue damage. In conclusion, treatment with DF2156A seems be effective in controlling tissue inflammation and dysfunction but its effects are highly dependent on the timing of the treatment start.