Risk of repeated drainage in pediatric septic arthritis: patient or method?

How drainage of septic arthritis should be performed remains controversial. The aim of the present study was to compare arthrocentesis (Ac) using double intra-articular needle lavage to arthrotomy (At) as first-line drainage treatment for pediatric hip and knee septic arthritis. The secondary objective was to identify risk factors of second articular drainage. A retrospective review of medical records of children with knee and hip septic arthritis was conducted. Inclusion criteria were: children treated for septic arthritis between 2014 and 2020 with a positive culture of joint fluid. Clinical, biological, radiographical and ultrasound data were recorded at presentation and during follow-up. Patients were divided into 2 groups according to the type of drainage performed: Ac or At. 25 hips and 44 knees were included, 42 treated by Ac (15 hips, 27 knees) and 27 by At (10 hips, 17 knees). There is no significant difference between Ac and At regarding the need for repeated drainage and Ac nor At was reported as risk factor for repeated drainage. The presence of associated musculoskeletal infection (MSI) was a significant risk factor of repeated drainage [odds ratio = 11.8; 95% confidence interval = 1.2-114.2; P < 0.001]. Significantly more associated MSI (P < 0.001), level I virulence germs (P < 0.001) and positive blood culture (<0.001) were found in patients who underwent repeated drainage. There was no significant difference between Ac and At regarding rate of repeated drainage. The risk factors for repeated drainage were: associated with MSI, virulent germs and positive blood culture.

Intraoperative neurophysiological monitoring in scoliosis surgery: literature review of the last 10 years.

INTRODUCTION: Patients with spinal deformities undergoing corrective surgery are at risk for iatrogenic spinal cord injury (SCI) and subsequent neurological deficit. Intraoperative neurophysiological monitoring (IONM) allows early detection of SCI which enables early intervention resulting in a better prognosis. The primary aim of this literature review was to search if there are threshold values of TcMEP and SSEP in the literature that are widely accepted as alert during IONM. The secondary aim was to update knowledge concerning IONM during scoliosis surgery. METHOD: PubMed/MEDLINE and Cochrane library electronic databases were used to search publication from 2012 to 2022. The following keywords were used: evoked potential, scoliosis, surgery, intraoperative monitoring and neurophysiological. We included all studies dealing with SSEP and TcMEP monitoring during scoliosis surgery. Two authors reviewed all titles and abstracts to identify studies that met the inclusion criteria. RESULTS: We included 43 papers. Rates of IONM alert and neurological deficit varied from 0.56 to 64% and from 0.15 to 8.3%, respectively. Threshold values varied from a loss of 50 to 90% for TcMEP amplitude, whereas it seems that a loss of 50% in amplitude and/or an increase of 10% of latency is widely accepted for SSEP. Causes of IONM changes most frequently reported were surgical maneuver. CONCLUSION: Concerning SSEP, a loss of 50% in amplitude and/or an increase of 10% of latency is widely accepted as an alert. For TcMEP, it seems that the use of highest threshold values can avoid unnecessary surgical procedure for the patient without increasing risk of neurological deficit.

The role of the prostaglandin D2 receptor, DP, in eosinophil trafficking.

Prostaglandin (PG) D2 is a major mast cell product that acts via two receptors, the D-type prostanoid (DP) and the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptors. Whereas CRTH2 mediates the chemotaxis of eosinophils, basophils, and Th2 lymphocytes, the role of DP has remained unclear. We report in this study that, in addition to CRTH2, the DP receptor plays an important role in eosinophil trafficking. First, we investigated the release of eosinophils from bone marrow using the in situ perfused guinea pig hind limb preparation. PGD2 induced the rapid release of eosinophils from bone marrow and this effect was inhibited by either the DP receptor antagonist BWA868c or the CRTH2 receptor antagonist ramatroban. In contrast, BWA868c did not inhibit the release of bone marrow eosinophils when this was induced by the CRTH2-selective agonist 13,14-dihydro-15-keto-PGD2. In additional experiments, we isolated bone marrow eosinophils from the femoral cavity and found that these cells migrated toward PGD2. We also observed that BWA868c inhibited this response to a similar extent as ramatroban. Finally, using immunohistochemistry we could demonstrate that eosinophils in human bone marrow specimens expressed DP and CRTH2 receptors at similar levels. Eosinophils isolated from human peripheral blood likewise expressed DP receptor protein but at lower levels than CRTH2. In agreement with this, the chemotaxis of human peripheral blood eosinophils was inhibited both by BWA868c and ramatroban. These findings suggest that DP receptors comediate with CRTH2 the mobilization of eosinophils from bone marrow and their chemotaxis, which might provide the rationale for DP antagonists in the treatment of allergic disease.

Hierarchy of eosinophil chemoattractants: role of p38 mitogen-activated protein kinase.

Several chemoattractants can regulate the recruitment of eosinophils to sites of inflammation, but the hierarchy among them is unknown. We observed here that eosinophil chemotaxis towards eotaxin or 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) was amplified up to sixfold in the presence of prostaglandin (PG) D2. This effect was only seen in eosinophils, and not in neutrophils or basophils. Pretreatment with the chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) antagonist ramatroban prevented the PGD2 enhancement of eosinophil migrations. In contrast, eotaxin or 5-oxo-ETE inhibited the migration of eosinophils towards PGD2. 5-oxo-ETE enhanced the chemotaxis to eotaxin, while eotaxin had no effect on 5-oxo-ETE-induced migration. 5-oxo-ETE induced the phosphorylation of p38 mitogen-activated protein kinase, and inhibition of p38 mitogen-activated protein kinase by SB-202190 converted the effect of 5-oxo-ETE on the chemotaxis to PGD2 from inhibition to enhancement. The presence of blood or plasma markedly decreased the sensitivity of eosinophils to eotaxin or 5-oxo-ETE, while responses to PGD2 were unaltered. In conclusion, PGD2 might be an initial chemoattractant, since it maintains its potency in the circulation and augments the responsiveness of eosinophils to other chemoattractants. In contrast, eotaxin seems to be an end-point chemoattractant, since it has reduced efficacy in blood and is capable of down-modulating eosinophil responsiveness to other chemoattractants.

On the mechanism of interaction of potent surmountable and insurmountable antagonists with the prostaglandin D2 receptor CRTH2.

Chemoattractant receptor-homologous molecule expressed on T helper 2 cells (CRTH2) has attracted interest as a potential therapeutic target in inflammatory diseases. Ramatroban, a thromboxane A2 receptor antagonist with clinical efficacy in allergic rhinitis, was recently found to also display potent CRTH2 antagonistic activity. Here, we present the pharmacological profile of three ramatroban analogs that differ chemically from ramatroban by either a single additional methyl group (TM30642), or an acetic acid instead of a propionic acid side chain (TM30643), or both modifications (TM30089). All three compounds bound to human CRTH2 stably expressed in human embryonic kidney 293 cells with nanomolar affinity. [3H]Prostaglandin D2 (PGD2) saturation analysis reveals that ramatroban and TM30642 decrease PGD2 affinity, whereas TM30643 and TM30089 exclusively depress ligand binding capacity (Bmax). Each of the three compounds acted as potent CRTH2 antagonists, yet the nature of their antagonism differed markedly. In functional assays measuring inhibition of PGD2-mediated 1) guanosine 5'-O-(3-thio)triphosphate binding, 2) beta-arrestin translocation, and 3) shape change of human eosinophils endogenously expressing CRTH2, ramatroban, and TM30642 produced surmountable antagonism and parallel rightward shifts of the PGD2 concentration-response curves. For TM30643 and TM30089, this shift was accompanied by a progressive reduction of maximal response. Binding analyses indicated that the functional insurmountability of TM30643 and TM30089 was probably related to long-lasting CRTH2 inhibition mediated via the orthosteric site of the receptor. A mechanistic understanding of insurmountability of CRTH2 antagonists could be fundamental for development of this novel class of anti-inflammatory drugs.

5-Oxo-6,8,11,14-eicosatetraenoic acid is a potent chemoattractant for human basophils.

BACKGROUND: 5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a chemoattractant for eosinophils and neutrophils, and the messenger RNA for its receptor, the oxo-eicosatetraenoic acid receptor (OXE), has been detected in several tissues. OBJECTIVES: This study aimed at clarifying the role of 5-oxo-ETE in the regulation of basophil function. METHODS: Basophil responses were determined in assays of flow-cytometric shape change, Ca(2+) flux, chemotaxis, and histamine release. Messenger RNA for OXE was detected by real-time PCR. RESULTS: We observed that human eosinophils were 3 to 10 times more sensitive to 5-oxo-ETE than neutrophils in flow-cytometric shape change and Ca(2+) flux assays, as estimated from the half-maximal responses of the cells. Basophils responded to 5-oxo-ETE in the shape change assay with a sensitivity similar to that of eosinophils. 5-Oxo-ETE was a weak inducer of Ca(2+) flux in basophils and did not cause histamine release but was a highly effective chemoattractant for basophils in the low nanomolar concentration range in a pertussis toxin-sensitive manner. In agreement with these functional studies, the messenger RNA for the 5-oxo-ETE receptor, OXE, was detectable in basophils as in monocytes, eosinophils, and neutrophils, but not in fibroblasts. Specimens from sinus mucosa, tonsils, and adenoids also contained detectable levels of messenger RNA for OXE. CONCLUSION: Our data suggest that 5-oxo-ETE is potentially involved in the regulation of basophil recruitment and might hence be a useful therapeutic target in atopic disease.