Preferential inhibition of adaptive immune system dynamics by glucocorticoids in patients after acute surgical trauma.

Glucocorticoids (GC) are a controversial yet commonly used intervention in the clinical management of acute inflammatory conditions, including sepsis or traumatic injury. In the context of major trauma such as surgery, concerns have been raised regarding adverse effects from GC, thereby necessitating a better understanding of how GCs modulate the immune response. Here we report the results of a randomized controlled trial (NCT02542592) in which we employ a high-dimensional mass cytometry approach to characterize innate and adaptive cell signaling dynamics after a major surgery (primary outcome) in patients treated with placebo or methylprednisolone (MP). A robust, unsupervised bootstrap clustering of immune cell subsets coupled with random forest analysis shows profound (AUC = 0.92, p-value = 3.16E-8) MP-induced alterations of immune cell signaling trajectories, particularly in the adaptive compartments. By contrast, key innate signaling responses previously associated with pain and functional recovery after surgery, including STAT3 and CREB phosphorylation, are not affected by MP. These results imply cell-specific and pathway-specific effects of GCs, and also prompt future studies to examine GCs' effects on clinical outcomes likely dependent on functional adaptive immune responses.

Preoperative High-Dose Methylprednisolone and Glycemic Control Early After Total Hip and Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: To evaluate the effect of a single preoperative dose of 125 mg methylprednisolone (MP) on glycemic homeostasis early after fast-track total hip and knee arthroplasty. METHODS: One-hundred thirty-four patients undergoing elective unilateral total hip arthroplasty and total knee arthroplasty were randomized (1:1) to preoperative intravenous MP 125 mg (group MP) or isotonic saline intravenous (group C). All procedures were performed under spinal anesthesia, using a standardized multimodal analgesic regime. The primary outcome was the change in plasma glucose 2 hours postoperatively, and secondary outcomes included plasma C-peptide concentrations, homeostatic model assessment (HOMA), HOMA-IR (insulin resistance), and HOMA-B (ß-cell function). Fasting blood samples were collected at baseline and 2, 6 (nonfasting), 24, and 48 hours after surgery with complete samples from 122 patients (group MP = 62, group C = 60) for analyses. RESULTS: MP patients had increased plasma glucose levels at 2 hours (adjusted mean [95% CI], 7.4 mmol·L [7.2-7.5] vs 6.0 mmol·L [5.9-6.2]; P = .023) and 6 hours (13.9 mmol·L [13.3-14.5] vs 8.4 mmol·L [7.8-9.0]; P < .001), and in plasma C-peptide 24 hours postoperatively (1675 pmol·L [1573-1778] vs 1248 pmol·L [1145-1351]; P < .001). An impaired insulin response was also observed in group MP as reflected by HOMA-B (P < .001). Additionally, HOMA-IR increased 24 hours postoperatively in group MP compared to group C (P < .001). Parameters were normalized 48 hours postoperatively. CONCLUSIONS: Preoperative administration of MP 125 mg resulted in a transient postoperative increase in plasma glucose and insulin resistance and impaired insulin secretion in response to hyperglycemia.

Acute pain management in burn patients: appraisal and thematic analysis of four clinical guidelines.

OBJECTIVE: Burn patients suffer excruciating pain due to their injuries and procedures related to surgery, wound care, and mobilization. Acute Stress Disorder, Post-Traumatic Stress Disorder, chronic pain and depression are highly prevalent among survivors of severe burns. Evidence-based pain management addresses and alleviates these complications. The aim of our study was to compare clinical guidelines for pain management in burn patients in selected European and non-European countries. We included pediatric guidelines due to the high rate of children in burn units. METHOD: The study had a comparative retrospective design using combined methodology of instrument appraisal and thematic analysis. Three investigators appraised guidelines from burn units in Denmark (DK), Sweden (SE), New Zealand (NZ), and USA using the AGREE Instrument (Appraisal of Guidelines for Research & Evaluation), version II, and identified core themes in the guidelines. RESULTS: The overall scores expressing quality in six domains of the AGREE instrument were variable at 22% (DK), 44% (SE), 100% (NZ), and 78% (USA). The guidelines from NZ and USA were highly recommended, the Swedish was recommended, whereas the Danish was not recommended. The identified core themes were: continuous pain, procedural pain, postoperative pain, pain assessment, anxiety, and non-pharmacological interventions. CONCLUSION: The study demonstrated variability in quality, transparency, and core content in clinical guidelines on pain management in burn patients. The most highly recommended guidelines provided clear and accurate recommendations for the nursing and medical staff on pain management in burn patients. We recommend the use of a validated appraisal tool such as the AGREE instrument to provide more consistent and evidence-based care to burn patients in the clinic, to unify guideline construction, and to enable interdepartmental comparison of treatment and outcomes.