Increased Neutrophil Adenosine A3 Receptor Expression Is Associated With Hemorrhagic Shock and Injury Severity in Trauma Patients
Bibliographic record
Abstract
Hypertonic saline (HS) has been investigated as an immune modulator following hemorrhagic shock and sepsis. The polymorphonuclear neutrophil (PMN) response to HS is regulated by the release of ATP, which is converted to adenosine and activates adenosine receptors. Binding to A3 adenosine receptors promotes PMN activation, and inhibition of A3 receptors improves the efficacy of HS resuscitation. A3 receptor expression of PMNs has not been previously evaluated in injured patients. Whole blood was obtained from 10 healthy volunteers and 60 injured patients within 2 h of injury. Inclusion criteria were blunt or penetrating injury with evidence of hypovolemic shock (systolic blood pressure [SBP] ≤90 mmHg and base deficit ≥6 mEq/L or need for blood transfusion) or evidence of severe traumatic brain injury including initial Glasgow Coma Scale score of 8 or less or evidence of traumatic brain injury on head computed tomography scan (head Abbreviated Injury Score ≥3) or intubation in the field or emergency department. A3 receptor expression was assessed by flow cytometry. Polymorphonuclear neutrophils were also exposed to fMLP or HS (20-40 mM) in vitro. Clinical data were collected including admission physiology, injury severity (Injury Severity Score [ISS]), development of multiple organ failure, and survival. In normal volunteers, less than 1% of PMNs expressed A3 receptors on the cell surface. A3 receptor expression was significantly higher in injured patients, and the level of expression correlated with the severity of injury (ISS ≥25: A3 positive PMN 36.6% vs. ISS <25: 16.2%; P = 0.019) and degree of hypovolemic shock (SBP ≤90 mmHg: A3 positive PMN 43.8% vs. SBP>90 mmHg: 20.6%; P = 0.008). Stimulation with fMLP or HS increased A3 expression in normal volunteers, but only in patients with ISS of less than 25 or without hypovolemic shock. A3 receptor expression on the surface of PMNs is upregulated by injury, and increased expression levels are associated with greater injury severity and hypovolemic shock. Hypertonic saline increases A3 expression of PMNs from healthy volunteers and less severely injured patients.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".