ReviewFrontiers in endocrinology2020
General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections.
Review in Frontiers in endocrinology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Pharmacological principles guiding prolonged glucocorticoid treatment in ARDS.Intensive care medicine · 2020Pooled it
- Early C-reactive protein reduction predicts survival in COVID-19 severe pneumonia treated with glucocorticoids.BMC pulmonary medicine · 2025Trial
- Prolonged higher dose methylprednisoloneThe European respiratory journal · 2023Trial
- ARDS and corticosteroids: beyond COVID-19.Pneumonia (Nathan Qld.) · 2026Review
- Systemic corticosteroids for severe community-acquired pneumonia: a narrative review of mechanisms and critical appraisal of recent trials in ICU.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Mechanism of Morchella polysaccharide in anti-fatigue: the role of the gut microbiota-metabolite axis in mice.NPJ science of food · 2026Article
- Evolutionary Integration and Glucocorticoid Regulation of the Respiratory System: Structure, Function, and Homeostatic Adaptation.Medical sciences (Basel, Switzerland) · 2026Review
- Glucocorticoid-Mediated Astrocytic L-Lactate Release Drives Chronic Postsurgical Pain via Spinal Neuronal Sensitization.Neurochemical research · 2026Article
- Cell-specific expression and signaling of glucocorticoid receptor isoforms over time in critically ill patients with a low inflammatory response.Critical care (London, England) · 2025Observational
- Corticosteroids in bacterial severe community-acquired pneumonia: lessons from recent trials.Frontiers in medicine · 2025Article
- Role of Nuclear Factor-Kappa B Activation and Inflammatory Biomarkers in Critically Ill Children.Indian journal of pediatrics · 2024Article
- Pilot investigations into the mechanistic basis for adverse effects of glucocorticoids in dysferlinopathy.Skeletal muscle · 2024Article
- Physiologically Based Pharmacokinetic Modeling: The Reversible Metabolism and Tissue-Specific Partitioning of Methylprednisolone and Methylprednisone in Rats.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Prolonged intensive care: muscular functional, and nutritional insights from the COVID-19 pandemic.Acute and critical care · 2024Article
- Critical illness-related corticosteroid insufficiency (CIRCI) - an overview of pathogenesis, clinical presentation and management.Frontiers in endocrinology · 2024Review
- Context is key: glucocorticoid receptor and corticosteroid therapeutics in outcomes after traumatic brain injury.Frontiers in cellular neuroscience · 2024Review
- Inflammation in Posttraumatic Stress Disorder: Dysregulation or Recalibration?Current neuropharmacology · 2024Article
- The Hypothalamus-pituitary-adrenocortical Response to Critical Illness: A Concept in Need of Revision.Endocrine reviews · 2023Article
- Theory and Practice of Glucocorticoids in COVID-19: Getting to the Heart of the Matter-A Critical Review and Viewpoints.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Macrophages in immunoregulation and therapeutics.Signal transduction and targeted therapy · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In critical illness, homeostatic corrections representing the culmination of hundreds of millions of years of evolution, are modulated by the activated glucocorticoid receptor alpha (GRα) and are associated with an enormous bioenergetic and metabolic cost. Appreciation of how homeostatic corrections work and how they evolved provides a conceptual framework to understand the complex pathobiology of critical illness. Emerging literature place the activated GRα at the center of all phases of disease development and resolution, including activation and re-enforcement of innate immunity, downregulation of pro-inflammatory transcription factors, and restoration of anatomy and function. By the time critically ill patients necessitate vital organ support for survival, they have reached near exhaustion or exhaustion of neuroendocrine homeostatic compensation, cell bio-energetic and adaptation functions, and reserves of vital micronutrients. We review how critical illness-related corticosteroid insufficiency, mitochondrial dysfunction/damage, and hypovitaminosis collectively interact to accelerate an anti-homeostatic active process of natural selection. Importantly, the allostatic overload imposed by these homeostatic corrections impacts negatively on both acute and long-term morbidity and mortality. Since the bioenergetic and metabolic reserves to support homeostatic corrections are time-limited, early interventions should be directed at increasing GRα and mitochondria number and function. Present understanding of the activated GC-GRα's role in immunomodulation and disease resolution should be taken into account when re-evaluating how to administer glucocorticoid treatment and co-interventions to improve cellular responsiveness. The activated GRα interdependence with functional mitochondria and three vitamin reserves (B1, C, and D) provides a rationale for co-interventions that include prolonged glucocorticoid treatment in association with rapid correction of hypovitaminosis.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.