{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:15:33Z","timestamp":1788444933859,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Critically ill patients frequently experienced acquired muscle dysfunction, which adversely affects outcomes. The relationship between calorie intake, muscle dysfunction and outcomes remains unclear. This study aims to determine if early calorie intake affects patients' outcomes through changes in skeletal muscle mass or quality, and to explore changes in muscle structure and underlying molecular pathways using limb muscle biopsies in a piglet model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This translational study combines data from a prospective observational study including critically ill patients and a 72\u2010h ventilated piglet model with early high calorie full enteral nutrition, both recording serial ultrasound measurements of limb muscle thickness and stiffness. Patients were classified into two trajectory groups based on thickness, stiffness and calorie intake. Adjusted mediation analysis quantified the effect of calorie intake on outcomes explained by muscle trajectories. The primary endpoint was ventilator\u2010free days at Day 28 (VFD28). In\u00a0vivo limb muscle biopsies from piglets were analysed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 102 patients, 21% and 28% exhibited decreased thickness and stiffness by Day 7, respectively; 36% received high\u2010calorie intake at Day 7. Patients categorized into the \u2018decreased trajectory group\u2019 for both thickness and stiffness showed lower VFD28 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) and longer ICU stay (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) compared to the \u2018stable trajectory group\u2019. High\u2010calorie intake was associated with significantly lower VFD28 (\u22128.7\u2009days [\u221214.7 to \u22121.7];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01), longer ICU stay (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) and higher ICU mortality (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). Decreased muscle trajectories mediated, respectively, 42% and 28% of the association between high\u2010calorie intake and VFD 28. The porcine model showed a limb muscle stiffness reduction associated with muscle fibre atrophy and increased intramuscular lipid content linked to decreased protein synthesis (IGF\u20101 and myostatin downregulation), increased autophagy (ATG5, ATG7 and P62 increased activity) and impaired fatty acid metabolism (carnitine palmitoyltransferase 1B reduced expression).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study demonstrates that early calorie intake in critically ill patients adversely affects muscle mass and quality, mediating negative outcomes. The porcine model helps elucidate underlying mechanisms, with early high\u2010calorie intake resulting in a metabolic oversupply state associated with metabolic disorders leading to muscle fibre atrophy and lipid accumulation. These results highlight the importance of targeted nutritional strategies to preserve muscle health in critically ill patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70355","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T05:46:42Z","timestamp":1786600002000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Changes in Muscle Mass and Quality Mediate the Effect of High\u2010Calorie Intake on Clinical Outcomes"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8246-6204","authenticated-orcid":false,"given":"Yassir","family":"Aarab","sequence":"first","affiliation":[{"name":"Saint Eloi Anesthesiology and Critical Care Medicine Montpellier University and Montpellier Teaching Hospital  Montpellier France"},{"name":"Intensive Care Unit Clinique Saint\u2010Jean Sud de France  Montpellier France"},{"name":"PhyMedExp University of Montpellier, INSERM U1046, CNRS UMR 9214  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Raynaud","sequence":"additional","affiliation":[{"name":"PhyMedExp University of Montpellier, INSERM U1046, CNRS UMR 9214  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9585-4521","authenticated-orcid":false,"given":"Mathieu","family":"Capdevila","sequence":"additional","affiliation":[{"name":"Saint Eloi Anesthesiology and Critical Care Medicine Montpellier University and Montpellier Teaching Hospital  Montpellier France"},{"name":"PhyMedExp University of Montpellier, INSERM U1046, CNRS UMR 9214  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelien","family":"Flatres","sequence":"additional","affiliation":[{"name":"PhyMedExp University of Montpellier, INSERM U1046, CNRS UMR 9214  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9rald","family":"Hugon","sequence":"additional","affiliation":[{"name":"PhyMedExp University of Montpellier, INSERM U1046, CNRS UMR 9214  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Lauret","sequence":"additional","affiliation":[{"name":"PhyMedExp University of Montpellier, INSERM U1046, CNRS UMR 9214  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1786-0088","authenticated-orcid":false,"given":"Nicolas","family":"Molinari","sequence":"additional","affiliation":[{"name":"Biostatistics Department Montpellier University and Montpellier Teaching Hospital  Montpellier 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