{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T10:03:35Z","timestamp":1784714615481,"version":"3.55.0"},"reference-count":22,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Resting energy expenditure (REE) rises during critical illness, but its determinants and prognostic relevance remain incompletely characterized. Identifying a circulating signal that tracks REE could provide a bedside surrogate for metabolic demand where indirect calorimetry is unavailable. This prospective pilot study described longitudinal trajectories of indirect calorimetry-measured REE, Sequential Organ Failure Assessment (SOFA) score, serum cortisol and insulin-like growth factor-1 (IGF-1) over two weeks in the intensive care unit (ICU), examined whether the REE trajectory was attenuated by adjustment for these variables, and generated preliminary effect-size and variance estimates for mortality. Methods: This single-center pilot study enrolled 39 critically ill adults at Evangelismos General Hospital (Athens, Greece); sample size was pragmatic, not based on an a priori power calculation. REE (Q-NRG metabolic monitor), cortisol and IGF-1 were measured at admission and days 5\u20137, 10\u201311 and 13\u201314, alongside SOFA. Trajectories were modeled with linear mixed-effects models using all available repeated measures. Confounding was assessed by adding SOFA, cortisol and IGF-1 as covariates and evaluating attenuation of the time effect; no formal mediation analysis was performed. Causes of missing data were quantified and a completers-only sensitivity analysis was undertaken. Mortality was analyzed by Cox regression with ICU length of stay as the time variable. Estimation was emphasized throughout; point estimates and 95% confidence intervals (CIs) are reported in preference to significance testing. Results: Mean age was 54.6 \u00b1 18.1 years; 69.2% were male; median admission SOFA was 6 (IQR 3\u20139). ICU and 28-day mortality were 20.5% (8\/39) and 10.3% (4\/39). REE\/kg rose from 25.3 \u00b1 3.7 to a peak of 27.2 \u00b1 4.2 kcal\/kg\/day by days 10\u201311 (likelihood-ratio \u03c72 = 17.2, p = 0.0006). Attrition was driven predominantly by discharge alive (18 of 23 patients missing at days 13\u201314) rather than death (n = 2), and the trajectory was preserved in a completers-only sensitivity analysis (\u03c72 = 9.13, p = 0.028). Cortisol declined (21.1 to 13.4 \u03bcg\/dL) and IGF-1 rose (80.0 to 105.4 ng\/mL); SOFA was essentially unchanged. REE did not correlate with SOFA, cortisol or IGF-1 at any time-point, and the time effect was not attenuated by adjustment for them. Admission REE was not associated with ICU mortality (HR 1.00, 95% CI 1.00\u20131.00). Higher admission REE was associated with a longer ICU stay, and this persisted after adjustment for body mass index (p = 0.026) and fat-free mass (p = 0.001). Age (HR 1.04, 95% CI 1.00\u20131.09) and admission SOFA (HR 1.18, 95% CI 0.98\u20131.44) were the covariates most associated with ICU mortality. Conclusions: REE rose progressively over the first 10\u201311 days of critical illness. Its trajectory was not attenuated by adjustment for SOFA, cortisol or IGF-1, which is compatible with\u2014but does not establish\u2014independence from the adrenal and somatotropic markers measured here. Neither REE nor these hormones were associated with mortality; age and disease severity remained the dominant prognostic factors, supporting a larger confirmatory study.<\/jats:p>","DOI":"10.3390\/nu18142391","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T09:20:39Z","timestamp":1784712039000},"page":"2391","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal Trajectories of Resting Energy Expenditure, Cortisol and IGF-1, and Disease Severity in Critically Ill Patients: A Prospective Pilot Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4142-2392","authenticated-orcid":false,"given":"Dimitrios","family":"Karayiannis","sequence":"first","affiliation":[{"name":"Department of Clinical Nutrition, Evangelismos General Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Elena","family":"Yatsulava","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Evangelismos General Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Katsigianni","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Evangelismos General Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2804-1208","authenticated-orcid":false,"given":"Georgios","family":"Poupouzas","sequence":"additional","affiliation":[{"name":"Pulmonary Department, Evangelismos General Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1067-8849","authenticated-orcid":false,"given":"Charikleia S.","family":"Vrettou","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, National Expertise Center for Rare Endocrine Diseases, Evangelismos Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6107-9400","authenticated-orcid":false,"given":"Vasileios","family":"Issaris","sequence":"additional","affiliation":[{"name":"Pulmonary Department, Evangelismos General Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efthymia","family":"Botoula","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, National Expertise Center for Rare Endocrine Diseases, Evangelismos Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4103-4931","authenticated-orcid":false,"given":"Marinella","family":"Tzanela","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, National Expertise Center for Rare Endocrine Diseases, Evangelismos Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3403-8977","authenticated-orcid":false,"given":"Dimitra A.","family":"Vassiliadi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, National Expertise Center for Rare Endocrine Diseases, Evangelismos Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4984-0476","authenticated-orcid":false,"given":"Alice G.","family":"Vassiliou","sequence":"additional","affiliation":[{"name":"1st Department of Critical Care Medicine, School of Medicine, National and Kapodistrian University of Athens, Evangelismos Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2219-7292","authenticated-orcid":false,"given":"Ioanna","family":"Dimopoulou","sequence":"additional","affiliation":[{"name":"1st Department of Critical Care Medicine, School of Medicine, National and Kapodistrian University of Athens, Evangelismos Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.clnesp.2025.06.036","article-title":"Serial measurement of energy expenditure in critically ill patients\u2014Feasibility and impact on nutrition provision","volume":"68","author":"Prange","year":"2025","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1186\/s13054-026-06102-w","article-title":"Time course of energy expenditure in persistent critical illness: A prospective multicentre study","volume":"30","author":"Oosterveld","year":"2026","journal-title":"Crit. Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s40560-021-00524-0","article-title":"Energy expenditure and indirect calorimetry in critical illness and convalescence: Current evidence and practical considerations","volume":"9","author":"Moonen","year":"2021","journal-title":"J. Intensive Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"104025","DOI":"10.1016\/j.resp.2023.104025","article-title":"Comparison of resting energy expenditure measured with metabolic cart and calculated with predictive formulas in critically ill patients on mechanical ventilation","volume":"311","author":"Taboni","year":"2023","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1016\/j.clnu.2023.07.011","article-title":"ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit","volume":"42","author":"Singer","year":"2023","journal-title":"Clin. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s13054-021-03508-6","article-title":"Energy delivery guided by indirect calorimetry in critically ill patients: A systematic review and meta-analysis","volume":"25","author":"Duan","year":"2021","journal-title":"Crit. Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1186\/s13613-025-01588-z","article-title":"The metabolic response to stress in critical illness: Updated review on the pathophysiological mechanisms, consequences, and therapeutic implications","volume":"15","author":"Mottale","year":"2025","journal-title":"Ann. Intensive Care"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.clnu.2025.01.004","article-title":"Nutrition therapy for critically ill patients\u2014Five key problems","volume":"46","author":"Kreymann","year":"2025","journal-title":"Clin. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.clnesp.2024.11.009","article-title":"Course of measured energy expenditure over the first 10 days of critical illness: A nested prospective study in an adult surgical ICU","volume":"65","author":"Veldsman","year":"2025","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_10","first-page":"1","article-title":"Novel insights into the neuroendocrinology of critical illness","volume":"143","year":"2000","journal-title":"Eur. J. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1210\/jc.2013-4115","article-title":"Endocrine responses to critical illness: Novel insights and therapeutic implications","volume":"99","author":"Boonen","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1056\/NEJMoa1214969","article-title":"Reduced cortisol metabolism during critical illness","volume":"368","author":"Boonen","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"476","DOI":"10.15537\/smj.2024.45.5.20240076","article-title":"Effect of cortisol and glycosylated-hemoglobin levels on mortality in intensive care unit","volume":"45","author":"Sen","year":"2024","journal-title":"Saudi Med. J."},{"key":"ref_14","first-page":"e1086","article-title":"Cortisol Levels During First Admission Day Are Associated with Clinical Outcomes in Surgical Critically Ill Patients","volume":"6","author":"Goder","year":"2024","journal-title":"Crit. Care Explor."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chapela, S.P., Simancas-Racines, D., Montalvan, M., Frias-Toral, E., Simancas-Racines, A., Muscogiuri, G., Barrea, L., Sarno, G., Mart\u00ednez, P.I., and Reberendo, M.J. (2023). Signals for Muscular Protein Turnover and Insulin Resistance in Critically Ill Patients: A Narrative Review. Nutrients, 15.","DOI":"10.3390\/nu15051071"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"R47","DOI":"10.1186\/cc10010","article-title":"Hormonal Status in Protracted Critical Illness and In-Hospital Mortality","volume":"15","author":"Sharshar","year":"2011","journal-title":"Crit. Care"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s40814-019-0499-1","article-title":"Guidelines for reporting non-randomised pilot and feasibility studies","volume":"5","author":"Lancaster","year":"2019","journal-title":"Pilot Feasibility Stud."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1186\/s13054-025-05628-9","article-title":"Cell-Specific Expression and Signaling of Glucocorticoid Receptor Isoforms over Time in Critically Ill Patients with a Low Inflammatory Response","volume":"29","author":"Poupouzas","year":"2025","journal-title":"Crit. Care"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Papanastasiou, P., Chaloulakou, S., Karayiannis, D., Almperti, A., Poupouzas, G., Vrettou, C.S., Issaris, V., Jahaj, E., Vassiliou, A.G., and Dimopoulou, I. (2025). Phase Angle Trajectory Among Critical Care Patients: Longitudinal Decline Predicts Mortality Independent of Clinical Severity Scores. Healthcare, 13.","DOI":"10.3390\/healthcare13121463"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Molenberghs, G., and Kenward, M.G. (2007). Missing Data in Clinical Studies, John Wiley & Sons.","DOI":"10.1002\/9780470510445"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/S0140-6736(07)61602-X","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement","volume":"370","author":"Altman","year":"2007","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"499","DOI":"10.2307\/2531021","article-title":"Sample-size formula for the proportional-hazards regression model","volume":"39","author":"Schoenfeld","year":"1983","journal-title":"Biometrics"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/14\/2391\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T09:29:52Z","timestamp":1784712592000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/14\/2391"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":22,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["nu18142391"],"URL":"https:\/\/doi.org\/10.3390\/nu18142391","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,22]]}}}