{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:51:57Z","timestamp":1791305517499,"version":"4.3.1"},"reference-count":67,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVES:<\/jats:title>\n                    <jats:p>To identify biological findings underlying skeletal muscle dysfunction in adults with critical illness and meta-analyze myofiber cross-sectional area and protein turnover variables.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DATA SOURCES:<\/jats:title>\n                    <jats:p>Six databases were electronically searched from inception to January 2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY SELECTION:<\/jats:title>\n                    <jats:p>We included original studies reporting biological findings obtained from skeletal muscle biopsies of adults with critical illness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DATA EXTRACTION:<\/jats:title>\n                    <jats:p>Bibliometrics, characteristics of the patients\/controls, and biological findings were extracted in duplicate. Descriptive statistics of biological findings were performed. Random-effects meta-analyses investigated mean differences (MDs) in myofiber cross-sectional area and protein turnover compared with controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DATA SYNTHESIS:<\/jats:title>\n                    <jats:p>\n                      From 22,035 titles screened, 75 studies (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 2,023 patients;\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 642 controls) published between 1988 and 2024 were included, with 48 unique patient datasets. Biopsies were mainly collected from vastus lateralis (64 [85%] studies) during the first ICU week (50% of studies) and post-ICU (9%). Biological findings included predominant type II myofiber atrophy with necrosis and structural degeneration, mitochondrial dysfunction, inflammatory\/fibrotic changes, and upregulated ubiquitin-proteasome\/autophagy pathways. Data from six studies (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 100 patients; 193 controls) indicated that cross-sectional area was 22% lower in patients with critical illness before (MD, \u2013689 \u00b5m\n                      <jats:sup>2<\/jats:sup>\n                      ; 95% CI, \u20131265 to \u2013113 \u00b5m\n                      <jats:sup>2<\/jats:sup>\n                      ;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.02) and after (MD, \u2013775 \u00b5m\n                      <jats:sup>2<\/jats:sup>\n                      ; 95% CI, \u20131512 to \u201337 \u00b5m\n                      <jats:sup>2<\/jats:sup>\n                      ;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.04) ICU discharge. Across seven studies (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 126 patients; 61 controls) protein synthesis was not significantly different in patients with critical illness compared with controls (MD, 0.007%\/hr; 95% CI, \u20130.010 to 0.027;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.36). Protein degradation pathway markers were significantly higher (standardized MD ranging, 0.5\u20131.7) in data from 11 studies (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 439 patients; 163 controls).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Muscle wasting during critical illness reflects multifaceted biological disturbances. While myofiber size is significantly lower in patients with critical illness, pooled analyses show no significant differences in muscle protein synthesis compared with non-ICU controls, whereas protein degradation markers are consistently higher.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/ccm.0000000000007288","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:27:25Z","timestamp":1786112845000},"page":"2636-2647","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Rethinking Muscle Wasting in Critical Illness: A Systematic Review and Meta-Analysis of Myofiber Size and Protein Turnover"],"prefix":"10.1097","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9099-2389","authenticated-orcid":false,"given":"Felipe","family":"Gonz\u00e1lez-Seguel","sequence":"first","affiliation":[{"name":"Department of Physical Therapy, College of Health Sciences, University of Kentucky, Lexington, KY."},{"name":"Center for Muscle Biology, University of Kentucky, Lexington, KY."},{"name":"School of Physical Therapy, Faculty of Medicine, Cl\u00ednica Alemana Universidad del Desarrollo, Santiago, Chile."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cayla M.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Medical Center Library, University of Kentucky, Lexington, KY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilo","family":"Caceres-Parra","sequence":"additional","affiliation":[{"name":"School of Physical Therapy, Faculty of Medicine, Cl\u00ednica Alemana Universidad del Desarrollo, Santiago, Chile."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Villablanca","sequence":"additional","affiliation":[{"name":"School of Physical Therapy, Faculty of Medicine, Cl\u00ednica Alemana Universidad del Desarrollo, Santiago, Chile."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"Olave","sequence":"additional","affiliation":[{"name":"School of Physical Therapy, Faculty of Medicine, Cl\u00ednica Alemana Universidad del Desarrollo, Santiago, Chile."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Mu\u00f1oz-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"School of Physical Therapy, Faculty of Medicine, Cl\u00ednica Alemana Universidad del Desarrollo, Santiago, Chile."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen","family":"Gustafson","sequence":"additional","affiliation":[{"name":"Oxford Allied Health Professions Research and Innovation Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline","family":"Cavallaro","sequence":"additional","affiliation":[{"name":"Department of Physiotherapy, The School of Health Sciences, The University of Melbourne, Melbourne, VIC, Australia."},{"name":"Physiotherapy Department, The Royal Melbourne Hospital, Melbourne, VIC, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Calulo Rivera","sequence":"additional","affiliation":[{"name":"Department of Physiotherapy, The School of Health Sciences, The University of Melbourne, Melbourne, VIC, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selina M.","family":"Parry","sequence":"additional","affiliation":[{"name":"Department of Physiotherapy, The School of Health Sciences, The University of Melbourne, Melbourne, VIC, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wen","sequence":"additional","affiliation":[{"name":"Center for Muscle Biology, University of Kentucky, Lexington, KY."},{"name":"Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY."},{"name":"Division of Biomedical Informatics, Department of Internal Medicine, College of Medicine, University of Kentucky, Lexington, KY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin F.","family":"Miller","sequence":"additional","affiliation":[{"name":"Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK."},{"name":"Oklahoma City Veterans Affairs Medical Center, Oklahoma City, OK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3844-3846","authenticated-orcid":false,"given":"Kirby P.","family":"Mayer","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, College of Health Sciences, University of Kentucky, Lexington, KY."},{"name":"Center for Muscle Biology, University of Kentucky, Lexington, KY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther E.","family":"Dupont-Versteegden","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, College of Health Sciences, University of Kentucky, Lexington, KY."},{"name":"Center for Muscle Biology, University of Kentucky, Lexington, KY."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"R1-20261006","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13054-022-04253-0","article-title":"The rate and assessment of muscle wasting during critical illness: A systematic review and meta-analysis.","volume":"27","author":"Fazzini","year":"2023","journal-title":"Crit Care"},{"key":"R2-20261006","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1007\/s00134-025-08186-4","article-title":"The intensive care medicine research agenda for the management of ICU acquired weakness: A multinational, interprofessional perspective.","volume":"51","author":"Eggmann","year":"2025","journal-title":"Intensive Care Med"},{"key":"R3-20261006","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1056\/NEJMra2104669","article-title":"Outcomes after critical illness.","volume":"388","author":"Herridge","year":"2023","journal-title":"N Engl J Med"},{"key":"R4-20261006","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1056\/NEJMoa1011802","article-title":"Functional disability 5 years after acute respiratory distress syndrome.","volume":"364","author":"Herridge","year":"2011","journal-title":"N Engl J Med"},{"key":"R5-20261006","first-page":"e1164","article-title":"Persistent fatigue, weakness, and aberrant muscle mitochondria in survivors of critical COVID-19.","volume":"6","author":"Mayer","year":"2024","journal-title":"Crit Care Explor"},{"key":"R6-20261006","doi-asserted-by":"crossref","first-page":"155142","DOI":"10.1016\/j.jcrc.2025.155142","article-title":"Acute skeletal muscle wasting in patients with acute kidney injury requiring continuous kidney replacement therapy: A prospective multicenter study.","volume":"89","author":"Mayer","year":"2025","journal-title":"J Crit Care"},{"key":"R7-20261006","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S0140-6736(24)01304-7","article-title":"Effect of high versus standard protein provision on functional recovery in people with critical illness (PRECISe): An investigator-initiated, double-blinded, multicentre, parallel-group, randomised controlled trial in Belgium and the Netherlands.","volume":"404","author":"Bels","year":"2024","journal-title":"Lancet"},{"key":"R8-20261006","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/S0140-6736(22)02469-2","article-title":"The effect of higher protein dosing in critically ill patients with high nutritional risk (EFFORT Protein): An international, multicentre, pragmatic, registry-based randomised trial.","volume":"401","author":"Heyland","year":"2023","journal-title":"Lancet"},{"key":"R9-20261006","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1056\/NEJMoa2209083","article-title":"Early active mobilization during mechanical ventilation in the ICU.","volume":"387","author":"Hodgson","year":"2022","journal-title":"N Engl J Med"},{"key":"R10-20261006","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1164\/rccm.202112-2780OC","article-title":"Muscle protein synthesis after protein administration in critical illness.","volume":"206","author":"Chapple","year":"2022","journal-title":"Am J Respir Crit Care Med"},{"key":"R11-20261006","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/s13613-025-01591-4","article-title":"Neuromuscular blockade and their monitoring in the intensive care unit: A multicenter observational prospective study.","volume":"15","author":"Hermann","year":"2025","journal-title":"Ann Intensive Care"},{"key":"R12-20261006","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1056\/NEJMoa1904710","article-title":"Early sedation with dexmedetomidine in critically ill patients.","volume":"380","author":"Shehabi","year":"2019","journal-title":"N Engl J Med"},{"key":"R13-20261006","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1056\/NEJMoa1901686","article-title":"Early neuromuscular blockade in the acute respiratory distress syndrome.","volume":"380","author":"Moss","year":"2019","journal-title":"N Engl J Med"},{"key":"R14-20261006","first-page":"CD006832","article-title":"Interventions for preventing critical illness polyneuropathy and critical illness myopathy.","volume":"2014","author":"Hermans","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"R15-20261006","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1164\/rccm.202304-0701ED","article-title":"The faltering evidence base for early rehabilitation.","volume":"208","author":"Cuthbertson","year":"2023","journal-title":"Am J Respir Crit Care Med"},{"key":"R16-20261006","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S2213-2600(18)30279-0","article-title":"Negative trials in critical care: Why most research is probably wrong.","volume":"6","author":"Laffey","year":"2018","journal-title":"Lancet Respir Med"},{"key":"R17-20261006","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1136\/thoraxjnl-2016-208312","article-title":"From skeletal muscle weakness to functional outcomes following critical illness: A translational biology perspective.","volume":"74","author":"Batt","year":"2019","journal-title":"Thorax"},{"key":"R18-20261006","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1001\/jama.2013.278481","article-title":"Acute skeletal muscle wasting in critical illness.","volume":"310","author":"Puthucheary","year":"2013","journal-title":"JAMA"},{"key":"R19-20261006","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1002\/jcsm.13285","article-title":"Impaired proteostatic mechanisms other than decreased protein synthesis limit old skeletal muscle recovery after disuse atrophy.","volume":"14","author":"Fuqua","year":"2023","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"R20-20261006","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1002\/jcsm.12470","article-title":"Muscle-specific changes in protein synthesis with aging and reloading after disuse atrophy.","volume":"10","author":"Miller","year":"2019","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"R21-20261006","doi-asserted-by":"crossref","DOI":"10.1113\/EP092474","article-title":"The effect of bed rest, unilateral limb immobilization and head-down tilt on muscle protein synthesis: A systematic review and meta-analysis.","author":"Prokopidis","year":"2025","journal-title":"Exp Physiol"},{"key":"R22-20261006","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1152\/japplphysiol.01125.2025","article-title":"Respiratory muscle dysfunction in mechanical ventilation: A systematic review and meta-analysis of biological mechanisms.","volume":"140","author":"Gonz\u00e1lez-Seguel","year":"2026","journal-title":"J Appl Physiol (1985)"},{"key":"R23-20261006","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s12874-018-0545-3","article-title":"Defining the process to literature searching in systematic reviews: A literature review of guidance and supporting studies.","volume":"18","author":"Cooper","year":"2018","journal-title":"BMC Med Res Methodol"},{"key":"R24-20261006","article-title":"Cellular and molecular findings of critical illness (CINAHL).","author":"Robinson","year":"2025","journal-title":"searchRxiv"},{"key":"R25-20261006","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/1471-2288-14-135","article-title":"Estimating the sample mean and standard deviation from the sample size, median, range and\/or interquartile range.","volume":"14","author":"Wan","year":"2014","journal-title":"BMC Med Res Methodol"},{"key":"R26-20261006","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1002\/jrsm.1232","article-title":"Estimating data from figures with a web-based program: Considerations for a systematic review.","volume":"8","author":"Burda","year":"2017","journal-title":"Res Synth Methods"},{"key":"R27-20261006","doi-asserted-by":"crossref","first-page":"5496","DOI":"10.3390\/jcm11195496","article-title":"Sex-specific aspects of skeletal muscle metabolism in the clinical context of intensive care unit-acquired weakness.","volume":"11","author":"Engelhardt","year":"2022","journal-title":"J Clin Med"},{"key":"R28-20261006","doi-asserted-by":"crossref","first-page":"e3686","DOI":"10.1371\/journal.pone.0003686","article-title":"Dysregulation of mitochondrial dynamics and the muscle transcriptome in ICU patients suffering from sepsis induced multiple organ failure.","volume":"3","author":"Fredriksson","year":"2008","journal-title":"PLoS ONE"},{"key":"R29-20261006","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1007\/s00134-003-2048-9","article-title":"Effects on skeletal muscle of intravenous glutamine supplementation to ICU patients.","volume":"30","author":"Tj\u00e4der","year":"2004","journal-title":"Intensive Care Med"},{"key":"R30-20261006","doi-asserted-by":"crossref","first-page":"3733","DOI":"10.3390\/nu14183733","article-title":"Variability in skeletal muscle protein synthesis rates in critically ill patients.","volume":"14","author":"Tj\u00e4der","year":"2022","journal-title":"Nutrients"},{"key":"R31-20261006","doi-asserted-by":"crossref","first-page":"E529","DOI":"10.1152\/ajpendo.00258.2003","article-title":"Extremity hyperinsulinemia stimulates muscle protein synthesis in severely injured patients.","volume":"286","author":"Gore","year":"2004","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"R32-20261006","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1177\/0148607102026006342","article-title":"Glutamine supplementation fails to affect muscle protein kinetics in critically ill patients.","volume":"26","author":"Gore","year":"2002","journal-title":"JPEN J Parenter Enteral Nutr"},{"key":"R33-20261006","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1042\/CS20110233","article-title":"Protein metabolism and gene expression in skeletal muscle of critically ill patients with sepsis.","volume":"122","author":"Klaude","year":"2012","journal-title":"Clin Sci (Lond)"},{"key":"R34-20261006","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1097\/00000658-200004000-00018","article-title":"Protein-sparing effect in skeletal muscle of growth hormone treatment in critically ill patients.","volume":"231","author":"Gamrin","year":"2000","journal-title":"Ann Surg"},{"key":"R35-20261006","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1046\/j.1365-2990.1998.00144.x","article-title":"Muscle fibre atrophy in critically ill patients is associated with the loss of myosin filaments and the presence of lysosomal enzymes and ubiquitin.","volume":"24","author":"Helliwell","year":"1998","journal-title":"Neuropathol Appl Neurobiol"},{"key":"R36-20261006","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/path.1711640406","article-title":"Necrotizing myopathy in critically-ill patients.","volume":"164","author":"Helliwell","year":"1991","journal-title":"J Pathol"},{"key":"R37-20261006","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1007\/s00134-014-3224-9","article-title":"Dynamics of myosin degradation in intensive care unit-acquired weakness during severe critical illness.","volume":"40","author":"Wollersheim","year":"2014","journal-title":"Intensive Care Med"},{"key":"R38-20261006","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1002\/jcsm.12922","article-title":"Systematic review and meta-analysis of protein intake to support muscle mass and function in healthy adults.","volume":"13","author":"Nunes","year":"2022","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"R39-20261006","first-page":"110","article-title":"Can the critically ill patient generate sufficient energy to facilitate exercise in the ICU?","volume":"21","author":"Bear","year":"2018","journal-title":"Curr Opin Clin Nutr Metab Care"},{"key":"R40-20261006","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1164\/rccm.201512-2344OC","article-title":"Mechanisms of chronic muscle wasting and dysfunction after an intensive care unit stay. A pilot study.","volume":"194","author":"Dos Santos","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"R41-20261006","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s40635-025-00755-7","article-title":"In vitro and in vivo muscle mass and strength during the first week of critical illness.","volume":"13","author":"Claassen","year":"2025","journal-title":"Intensive Care Med Exp"},{"key":"R42-20261006","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1007\/s00134-025-07949-3","article-title":"Altered muscle transcriptome as molecular basis of long-term muscle weakness in survivors from critical illness.","volume":"51","author":"Uzun Ayar","year":"2025","journal-title":"Intensive Care Med"},{"key":"R43-20261006","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.clnu.2025.10.001","article-title":"The effect of enteral glycine on plasma glycine and muscle structure, size, and function in the critically ill: A randomized controlled trial.","volume":"54","author":"Ali Abdelhamid","year":"2025","journal-title":"Clin Nutr"},{"key":"R44-20261006","doi-asserted-by":"crossref","first-page":"1553471","DOI":"10.3389\/fphys.2025.1553471","article-title":"A novel short-course, low-intensity blood-flow-restricted exercise (BFRE) regimen to study satellite cell function in critical illness survivors with sustained muscle atrophy following intensive care unit-acquired weakness (ICUAW).","volume":"16","author":"Mathur","year":"2025","journal-title":"Front Physiol"},{"key":"R45-20261006","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1093\/ajrccm\/aamag086","article-title":"Increasing protein dose does not further augment muscle protein synthesis in critical illness: A randomized, controlled clinical trial.","volume":"212","author":"Summers","year":"2026","journal-title":"Am J Respir Crit Care Med"},{"issue":"Pt 15","key":"R46-20261006","doi-asserted-by":"crossref","first-page":"3883","DOI":"10.1113\/jphysiol.2011.206193","article-title":"Novel events in the molecular regulation of muscle mass in critically ill patients.","volume":"589","author":"Constantin","year":"2011","journal-title":"J Physiol"},{"key":"R47-20261006","doi-asserted-by":"crossref","first-page":"e18090","DOI":"10.1371\/journal.pone.0018090","article-title":"Activated protein synthesis and suppressed protein breakdown signaling in skeletal muscle of critically ill patients.","volume":"6","author":"Jespersen","year":"2011","journal-title":"PLoS One"},{"key":"R48-20261006","doi-asserted-by":"crossref","first-page":"E633","DOI":"10.1210\/jc.2010-2563","article-title":"Insufficient activation of autophagy allows cellular damage to accumulate in critically ill patients.","volume":"96","author":"Vanhorebeek","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"R49-20261006","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1164\/rccm.201209-1649OC","article-title":"Critical illness myopathy and GLUT4: Significance of insulin and muscle contraction.","volume":"187","author":"Weber-Carstens","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"R50-20261006","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1136\/thoraxjnl-2014-206225","article-title":"Increased expression of GDF-15 may mediate ICU-acquired weakness by down-regulating muscle microRNAs.","volume":"70","author":"Bloch","year":"2015","journal-title":"Thorax"},{"key":"R51-20261006","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1097\/CCM.0b013e31822d7c18","article-title":"Muscle atrophy and preferential loss of myosin in prolonged critically ill patients.","volume":"40","author":"Derde","year":"2012","journal-title":"Crit Care Med"},{"key":"R52-20261006","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/S2213-2600(13)70183-8","article-title":"Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: A subanalysis of the EPaNIC trial.","volume":"1","author":"Hermans","year":"2013","journal-title":"Lancet Respir Med"},{"key":"R53-20261006","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1042\/CS20060265","article-title":"Proteasome proteolytic activity in skeletal muscle is increased in patients with sepsis.","volume":"112","author":"Klaude","year":"2006","journal-title":"Clin Sci (Lond)"},{"key":"R54-20261006","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.clnu.2004.11.002","article-title":"An assay of microsomal membrane-associated proteasomes demonstrates increased proteolytic activity in skeletal muscle of intensive care unit patients.","volume":"24","author":"Klaude","year":"2005","journal-title":"Clin Nutr"},{"key":"R55-20261006","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1007\/s00134-017-4758-4","article-title":"Mechanism of ICU-acquired weakness: Skeletal muscle loss in critical illness.","volume":"43","author":"Batt","year":"2017","journal-title":"Intensive Care Med"},{"key":"R56-20261006","first-page":"96","article-title":"Metabolic aspects of muscle wasting during critical illness.","volume":"23","author":"van Gassel","year":"2020","journal-title":"Curr Opin Clin Nutr Metab Care"},{"key":"R57-20261006","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3109\/10408363.2011.586171","article-title":"Proteolysis in illness-associated skeletal muscle atrophy: From pathways to networks.","volume":"48","author":"Wing","year":"2011","journal-title":"Crit Rev Clin Lab Sci"},{"key":"R58-20261006","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1097\/CCM.0000000000001652","article-title":"Pharmacological therapy for the prevention and treatment of weakness after critical illness: A systematic review.","volume":"44","author":"Shepherd","year":"2016","journal-title":"Crit Care Med"},{"key":"R59-20261006","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1186\/s13054-022-04101-1","article-title":"Muscular myostatin gene expression and plasma concentrations are decreased in critically ill patients.","volume":"26","author":"Grunow","year":"2022","journal-title":"Crit Care"},{"key":"R60-20261006","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1007\/s00134-017-4757-5","article-title":"The ICM research agenda on intensive care unit-acquired weakness.","volume":"43","author":"Latronico","year":"2017","journal-title":"Intensive Care Med"},{"key":"R61-20261006","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.bja.2023.11.052","article-title":"Persistent inflammation, immunosuppression, and catabolism syndrome (PICS): A review of definitions, potential therapies, and research priorities.","volume":"132","author":"Chadda","year":"2024","journal-title":"Br J Anaesth"},{"key":"R62-20261006","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.ccc.2024.08.011","article-title":"Skeletal muscle: A critical organ for survival and recovery in critical illness.","volume":"41","author":"Lees","year":"2025","journal-title":"Crit Care Clin"},{"key":"R63-20261006","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1097\/CCM.0000000000003263","article-title":"Impact of very early physical therapy during septic shock on skeletal muscle: A randomized controlled trial.","volume":"46","author":"Hickmann","year":"2018","journal-title":"Crit Care Med"},{"key":"R64-20261006","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1002\/jcsm.12428","article-title":"Muscle wasting and function after muscle activation and early protocol-based physiotherapy: An explorative trial.","volume":"10","author":"Wollersheim","year":"2019","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"R65-20261006","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1113\/JP285616","article-title":"Current limitations and future opportunities of tracer studies of muscle ageing.","volume":"603","author":"O\u2019Reilly","year":"2025","journal-title":"J Physiol"},{"key":"R66-20261006","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1152\/japplphysiol.00855.2019","article-title":"CORP: The use of deuterated water for the measurement of protein synthesis.","volume":"128","author":"Miller","year":"2020","journal-title":"J Appl Physiol (1985)"},{"key":"R67-20261006","doi-asserted-by":"crossref","first-page":"e108885","DOI":"10.1136\/bmjopen-2025-108885","article-title":"Trajectories of Recovery after ACutE and cRitical illness (TRACER): A prospective observational study protocol.","volume":"15","author":"Gonz\u00e1lez-Seguel","year":"2025","journal-title":"BMJ Open"}],"container-title":["Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1097\/CCM.0000000000007288","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:01:57Z","timestamp":1791302517000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1097\/CCM.0000000000007288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":67,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1097\/ccm.0000000000007288","relation":{},"ISSN":["0090-3493","1530-0293"],"issn-type":[{"value":"0090-3493","type":"print"},{"value":"1530-0293","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]}}}