ArticleAmerican journal of respiratory and critical care medicine2015
Diaphragm muscle fiber weakness and ubiquitin-proteasome activation in critically ill patients.
Article in American journal of respiratory and critical care medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05191433 (Effects of Mechanical Ventilation on the Diaphragm in COVID-19 Intensive Care Patients. A Post-mortem Pathology Study.), which is not on this map. Cited by 110 papers, 2 of them syntheses that pooled it.
What it found
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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.
Effects of Mechanical Ventilation on the Diaphragm in COVID-19 Intensive Care Patients. A Post-mortem Pathology Study.
Who cites it
110 citing papers in PubMed, 2 syntheses or guidelines pooled it, 224 citations in OpenAlex.
- Respiratory muscle dysfunction in mechanical ventilation: a systematic review and meta-analysis of biological mechanisms.Journal of applied physiology (Bethesda, Md. : 1985) · 2026Pooled it
- Diaphragm ultrasound to predict weaning outcome: systematic review and meta-analysis.Anaesthesiology intensive therapy · 2022Pooled it
- Effects of levosimendan on respiratory muscle function in patients weaning from mechanical ventilation.Intensive care medicine · 2019Trial
- VIDD or CIADD? The ventilator remains a bona fide culprit.BMC anesthesiology · 2026Article
- Assessment of the role of inflammation-linked signaling pathways in ventilator-induced diaphragmatic dysfunction in rats by transcriptome RNA-seq.BMC molecular and cell biology · 2026Article
- Myosin Post-Translational Modifications Associated With Critical Illness Myopathy.Acta physiologica (Oxford, England) · 2026Article
- Species-specific effects of positive end-expiratory pressure on diaphragm and chest wall geometry in mice, rats, and humans.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Article
- The contribution of mechanical ventilation to critical illness-associated diaphragm dysfunction: a critical appraisal.Critical care (London, England) · 2026Review
- Loss of Myonuclei and Transcriptional Activity During Diaphragm Atrophy in Critically Ill Patients.Journal of cachexia, sarcopenia and muscle · 2026Article
- Muscle satellite cell dysfunction in critical illness: niche biology, regenerative failure, and implications for recovery.Frontiers in cell and developmental biology · 2026Review
- Small-Molecule Targeting MuRF1 Protects Against Denervation-Induced Diaphragmatic Dysfunction: Underlying Molecular Mechanisms.Journal of cachexia, sarcopenia and muscle · 2025Article
- Application of neurally adjusted ventilatory assist (NAVA): a narrative review.Journal of thoracic disease · 2025Review
- Effectiveness of diaphragmatic ultrasound as a predictor of successful weaning from mechanical ventilation.Journal of clinical monitoring and computing · 2025Observational
- Ventilator-induced diaphragmatic dysfunction: pathophysiology, monitoring and advances in potential treatment and prevention.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- The effect of mechanical ventilation on respiratory muscle echogenicity in critically ill children: an observational cohort study.BMC pediatrics · 2025Observational
- Diaphragm Pacing in Early Critical Illness? A Plea for a Super-Relaxed Approach.American journal of respiratory and critical care medicine · 2025Article
- Blowing in the Wind: The Uncertain Impact of Inspiratory Muscle Strength Training in ICU Patients.American journal of respiratory and critical care medicine · 2025Article
- Diaphragm Function in Health and Disease.Advances in experimental medicine and biology · 2025Review
- Intraoperative phrenic nerve stimulation to prevent diaphragm fiber weakness during thoracic surgery.PloS one · 2025Article
- Impact of COVID-19 on Diaphragmatic Function: Understanding Multiorgan Involvement and Long-Term Consequences.Journal of clinical medicine · 2024Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 3 countries.
Funding
Abstract
rationaleThe clinical significance of diaphragm weakness in critically ill patients is evident: it prolongs ventilator dependency, and increases morbidity and duration of hospital stay. To date, the nature of diaphragm weakness and its underlying pathophysiologic mechanisms are poorly understood.
objectivesWe hypothesized that diaphragm muscle fibers of mechanically ventilated critically ill patients display atrophy and contractile weakness, and that the ubiquitin-proteasome pathway is activated in the diaphragm.
methodsWe obtained diaphragm muscle biopsies from 22 critically ill patients who received mechanical ventilation before surgery and compared these with biopsies obtained from patients during thoracic surgery for resection of a suspected early lung malignancy (control subjects). In a proof-of-concept study in a muscle-specific ring finger protein-1 (MuRF-1) knockout mouse model, we evaluated the role of the ubiquitin-proteasome pathway in the development of contractile weakness during mechanical ventilation. MEASUREMENTS AND MAIN
resultsBoth slow- and fast-twitch diaphragm muscle fibers of critically ill patients had approximately 25% smaller cross-sectional area, and had contractile force reduced by half or more. Markers of the ubiquitin-proteasome pathway were significantly up-regulated in the diaphragm of critically ill patients. Finally, MuRF-1 knockout mice were protected against the development of diaphragm contractile weakness during mechanical ventilation.
conclusionsThese findings show that diaphragm muscle fibers of critically ill patients display atrophy and severe contractile weakness, and in the diaphragm of critically ill patients the ubiquitin-proteasome pathway is activated. This study provides rationale for the development of treatment strategies that target the contractility of diaphragm fibers to facilitate weaning.
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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.