Biological responses during high-dose protein nutrition in the critically ill: a randomized controlled trial
Bibliographic record
Abstract
Background Reduced protein intake is associated with adverse outcomes in critically ill patients. Paradoxically, large-scale randomized controlled trials have failed to demonstrate a beneficial effect of protein supplementation, perhaps because the dose required to achieve an anabolic response is unknown, and because biological mechanisms that determine individual patient responses to nutrition are poorly understood. Objectives The objective of this study was to determine the effect of exogenous protein dose on whole-body protein balance (WBPB) and associated biological markers of metabolic response. Methods We conducted a randomized controlled trial to determine the effect of high dose (2.5 g/kg/d by parenteral amino acid infusion for 48 h) compared with usual (0.8 g/kg/d) or moderate (1.75 g/kg/d) doses on WBPB. By measuring 13 C-leucine stable isotope kinetics, whole-body protein synthesis and breakdown were evaluated before and after the intervention. As a comprehensive and well-annotated method to achieve untargeted biomarker identification, the blood transcriptome was interrogated by RNA sequencing every 12 h to identify molecular signatures associated with increases in WBPB during protein supplementation. Results Thirty-three patients were randomly assigned, and 25 completed the study. The increase in WBPB for the high-dose group was 10.0±3.7, and that for the moderate and usual-dose groups were 6.7±2.9 and 6.6±3.6, μmol/kg/h (mean±SEM) respectively. After adjusting for baseline WBPB, high dose ( P = 0.036 vs. usual dose, P = 0.047 vs. moderate dose), but not moderate dose ( P = 0.893 vs. usual dose) protein led to larger increases in WBPB. Increased WBPB was associated with lower baseline protein balance (R 2 = 0.18, P = 0.03), and reduced expression of a distinct neutrophil bactericidal gene signature (normalized enrichment score = −1.613, P adj = 0.003). Conclusions Larger increases in WBPB were observed in critically ill patients receiving a high-dose protein supplementation strategy, and these increases were associated with a biological program reflecting neutrophil-mediated bacterial killing. Clinical Trial Registration ClinicalTrials.gov NCT02865408.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.004 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 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 source (direct Gemma or distilled Codex), 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".