{"paper_id":"361cddac-a7f0-4ea8-9bd2-343bf619d69e","body_text":"The U-shaped Curve of Energy Supply in the First 72 Hours of Critical Illness May Apply Only to Patients with Normal Body Mass Index: A Post-hoc Analysis of a Prospective Observational Multicenter Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The U-shaped Curve of Energy Supply in the First 72 Hours of Critical Illness May Apply Only to Patients with Normal Body Mass Index: A Post-hoc Analysis of a Prospective Observational Multicenter Study Youquan Wang, Yanjuan Wang, Yao Fu, Lingling Bao, Dong Zhang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6005098/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective Nutritional support is crucial for critically ill patients. Body mass index (BMI) represents nutritional reserves to some extent, but it is unclear whether the U-shaped relationship between caloric delivery during the acute phase of critical illness and prognosis applies to patients across all BMI categories. Methods This secondary analysis of a multicenter prospective observational study, which included patients who were admitted to the intensive care unit (ICU) for at least 3 days. The patients were divided into two subgroups based on BMI: normal BMI and overweight (BMI > 25 kg/m²). We used univariate and multivariate Cox regression analyses to investigate the relationship between calorie delivery within the first 72 hours of ICU admission and 28-day mortality, and to explore whether a non-linear relationship exists between the two. Results A total of 361 patients were included in the final analysis, including 272 in the normal BMI subgroup and 89 in the overweight subgroup. In the normal BMI subgroup Cox regression, there was a significant non-linear relationship ( P = 0.003) and association ( P = 0.002) between daily delivered calories and 28-day mortality. Increasing the daily delivered calories from 0 to 18 kcal/kg/day was associated with decreasing mortality (hazard ratio (HR) 0.892, 95% CI 0.816–0.975), while the daily delivered calories > 18 kcal/kg/day was associated with increasing mortality (HR 1.116, 95% CI 1.016–1.227)); In the overweight subgroup, higher daily delivered calories was also observed to increase mortality (HR 1.124, 95% CI 1.043–1.211, P = 0.003), but this non-linear relationship disappeared (P = 0.466). After adjustment, the above results still hold up. Conclusions The U-shaped relationship between daily delivered calories within the first 72 hours of ICU admission and 28-day mortality in critically ill patients applies only to those with BMI < 25 kg/m², and no such U-shaped curve was observed in patients with BMI > 25 kg/m². Further research is still needed to validate this conclusion. Critically ill patients Acute gastrointestinal injury Body mass index Feeding strategies Nutrition Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Introduction Malnutrition is prevalent among critically ill patients, particularly those who are admitted to the intensive care unit (ICU). This is frequently attributed to inadequate nutrition prior to ICU admission and the profound hyper-catabolic state induced by conditions such as sepsis and trauma, as outlined in the European Society of Intensive Care Medicine's (ESICM) guidelines ( 1 ). This leads to immune impairment, increased infection susceptibility, compromised healing, and ultimately higher mortality rates in critically ill patients ( 1 , 2 ). Nutritional support plays a crucial role in managing critically ill patients and can be administered through enteral feeding or parenteral feeding. Parenteral nutrition (PN) is employed when enteral nutrition (EN) is inadequate or not feasible. However, the optimal dosage of nutritional support during the early phase of critical illness remains controversial ( 3 ). Zusman et al. first revealed the \"U-shaped curve\" of calorie supply in critically ill patients through retrospective studies ( 4 ), indicating that both insufficient and excessive calorie supply are detrimental. The most beneficial energy supply may be one that reaches about 70% of the resting energy expenditure on average per day. Overfeeding can impose a digestive burden, suppress beneficial metabolic processes such as autophagy and ketosis, and may also lead to \"hibernating mitochondria to die of overwork ( 5 , 6 , 7 ).\" This theory explains the existence of the \"U-shaped curve,\" showing that higher nutritional supply is not always better. The subsequent PROTINVENT study also suggests that protein supply, like calories, may follow a \"U-shaped curve,\" with both excessive and insufficient protein intake being associated with poor prognosis in critically ill patients ( 8 ). Gradual feeding may be optimal, aligning with the feeding strategies recommended by the ESPEN guidelines ( 9 ). However, the harm caused by inadequate feeding may vary for each patient. During the acute phase of critical illness, the body is in a state of high catabolism ( 7 , 10 ), and patients with poor nutritional reserves may require more nutritional support, whereas the harm of inadequate feeding may be less significant for those with better nutritional reserves ( 11 , 12 ). Body mass index (BMI) may, to some extent, represent nutritional reserves ( 13 ). Therefore, we hypothesize that the \"U-shaped curve\" of energy supply applies only to patients with a normal BMI, but not to those with a BMI greater than 25 kg/m². 2. Methods 2.1 Participants We used data from a prospective, observational, nationwide study conducted between September 2014 and December 2014 in China to investigate the association of nutrition support with prognosis in critically ill patients with acute gastrointestinal injury (AGI) ( 14 ) . The names and geographical locations of the 12 teaching hospitals are in the Supplementary document. The project protocols followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines ( 15 ). Patients meeting the ESICM's definition and grading system for AGI were eligible for inclusion if they also received nutrition support within 72 hours of admission ( 16 ). Individuals with severe cardiovascular disease, post-cardiac arrest, chronic end-stage organ failure, malignancy, Crohn’s disease, ulcerative colitis, or short bowel syndrome, as well as those who died within 72 hours or were hospitalized for less than 72 hours before AGI was diagnosed, were excluded from this study. The study was conducted with approval from the ethics committee of the First Hospital of Jilin University in December 2012 (NO. 2012-088). 2.2 Data collection The enrolled patients were categorized into subgroups based on the BMI cut-off values from previous studies ( 17 , 18 ), with one subgroup being the normal BMI (18.5 ≤ BMI < 25 kg/m²) and the other subgroup being the overweight (BMI ≥ 25 kg/m²). For individuals with a BMI < 25 kg/m², actual body weight (ABW) was used to determine energy requirements. Moreover, for those with a BMI ≥ 25 kg/m², the reference (adjusted) body weight was replaced with the ideal body weight (IBW). The IBW was calculated by subtracting 100 (for males) or 106 (for females) from 0.9 multiplied by the height in centimeters. Additionally, when calculating energy requirements, it was considered to include 20% of the excess weight (the difference between the ABW and IBW) in addition to the IBW ( 19 ). The nutritional EN and PN supply information of patients in the first 72 hours of ICU admission were collected. And collected data also included general demographics, primary diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE II) score, AGI grade, and 28-day mortality. These parameters were used for comprehensive analysis and evaluation. Data was thoroughly screened for missing information and any implausible or outlier values. 2.3 Statistical analyses Continuous variables were expressed as means and standard deviations for normally distributed variables using the t-test. The median and interquartile range (IQR) were reported for non-normally distributed variables, and the Kruskal-Wallis test was employed for evaluation. Categorical variables were compared using the Chi-squared test. We performed a subgroup analysis based on whether the patients had a BMI > 25kg/m 2 . Initially an unadjusted Cox proportional hazards model for 28-day mortality was used, with the daily delivered calories entered as a continuous variable. Since the effects of daily delivered calories were considered to be non-linear, the percent was modeled as a restricted cubic spline with pre-specified knots. Subsequently, the Cox regression results were adjusted for potential risk factors affecting mortality in different subgroups to explore the association and non-linear relationship between daily delivered calories and the adjusted hazard ratio (HR) for 28-day mortality. Non-linearity was tested by ANOVA. An adjusted model with covariates selected based on univariate analysis. Multicollinearity was assessed by variation inflation factors and R 2 . A P value < 0.05 was considered significant. The statistical analysis was carried out using SPSS for Mac version 26(SPSS Inc, Chicago, IL, USA) and Rv4.3.1(R Foundation for Statistical Computing, Vienna, Austria) using RStudio v1.0.136 (RStudio Inc, Boston, MA, USA) 3. Results 3.1 Baseline characteristics A total of 443 patients were initially enrolled, but 64 individuals were excluded from the analysis due to missing nutrition data or AGI grade, treatment abandoning, or a hospitalization duration of less than 72 hours. Due to the small sample sizes with underweight (BMI < 18.5 kg/m²) (10 individuals) and obese (BMI ≥ 30 kg/m²) (8 individuals), they were excluded from the final analysis for robust statistical purposes. The final sample size for analysis included 361 patients who met all the inclusion criteria. All patients were divided into two subgroups according to their BMI, with 272 patients (75.3%) in the normal BMI subgroup, and 89 patients (24.7%) in the overweight subgroup (Fig. 1 and Table 1 ). The daily average delivered calories over the first 72 hours in the normal BMI subgroup and the overweight subgroup is shown in Fig. 2 . Table 1 Clinical and demographic data for development and validation cohort. Variables Normal BMI subgroup Overweight subgroup Total (n = 272) Survived (n = 228) Died within 28 days (n = 44) P value Total (n = 89) Survived (n = 75) Died within 28 days (n = 14) P value Age, y 61.8 ± 18.7 61.5 ± 18.0 63.8 ± 22.1 0.443 57.6 ± 18.1 56.8 ± 17.5 62.1 ± 20.6 0.309 Gender Male 183 (67.3) 154 (67.5) 29 (65.9) 0.832 59 (66.3) 50 (66.7) 9 (64.3) 0.863 Female 89 (22.7) 74 (32.5) 16 (34.1) 30 (33.7) 25 (33.3) 5 (35.7) BMI 22.6 ± 1.5 22.7 ± 1.5 22.2 ± 1.7 0.098 26.7 ± 1.2 26.5 ± 1.1 27.3 ± 1.5 0.078 Primary diagnosis 0.514 0.101 Neurologic 55 (20.2) 47 (20.6) 8 (18.2) 16 (18.0) 10 (13.3) 6 (42.9) Circulatory 18 (6.6) 16 (7.0) 2 (4.5) 5 (5.6) 4 (5.3) 1 (7.1) Respiratory 116 (42.6) 99 (43.4) 17 (38.6) 46 (51.7) 41 (54.7) 5 (35.7) Multi trauma 18 (6.6) 16 (7.0) 2 (4.5) 5 (5.6) 5 (6.7) 0 (0) Others 65 (23.9) 50 (21.9) 15 (34.1) 17 (19.1) 15 (20.0) 2 (14.3) Severity of illness a APACHE II score 16 ( 12 – 22 ) 15 ( 11 – 20 ) 22 ( 18 – 26 ) < 0.001 16 ( 12 – 21 ) 15 ( 10 – 18 ) 22 ( 17 – 25 ) 0.005 SOFA score 6 ( 3 – 8 ) 5 ( 3 – 8 ) 8 ( 5 – 10 ) < 0.001 6 ( 3 – 10 ) 5 ( 3 – 7 ) 8 ( 4 – 12 ) 0.009 mNUTRIC 5 ( 4 – 6 ) 5 ( 3 – 6 ) 6 ( 5 – 7 ) < 0.001 4 ( 3 – 6 ) 4 ( 3 – 6 ) 5 ( 4 – 7 ) 0.122 AGI grade 0.003 0.831 I 102 (37.5) 91 (39.9) 11 (25.0) 34 (38.2) 30 (40.0) 4 (28.6) II 129 (47.4) 110 (48.2) 19 (43.2) 36 (40.4) 32 (42.7) 4 (28.6) III 28 (10.3) 20 (8.8) 8 (18.2) 16 (18.0) 13 (17.3) 3 (21.4) IV 13 (4.8) 7 (3.1) 6 (13.6) 3 (3.4) 0 (0) 3 (21.4) Underlying disease Hypertension 137 (50.4) 118 (51.8) 19 (43.2) 0.298 57 (64.0) 48 (64.0) 9 (64.3) 0.984 Diabetes 86 (31.7) 72 (31.7) 14 (31.8) 0.990 26 (29.2) 21 (28.0) 5 (35.7) 0.560 Primary AGI 143 (52.6) 119 (52.2) 24 (54.5) 0.775 35 (39.3) 28 (37.3) 7 (50.0) 0.373 Mechanical ventilation 181 (66.5) 144 (63.2) 37 (84.1) 0.007 56 (62.9) 45 (60.0) 11 (78.6) 0.187 Sepsis 115 (42.3) 97 (42.5) 18 (40.9) 0.869 37 (41.6) 29 (38.7) 8 (57.1) 0.198 EN start time, h 48 (24–72) 48 (24–72) 48 (24–72) 0.795 48 (24–72) 48 (24–72) 48 (24–54) 0.765 EN initial rate, ml/h 20 ( 20 – 20 ) 20 ( 20 – 20 ) 20 ( 20 – 20 ) 0.946 20 ( 20 – 20 ) 20 ( 20 – 20 ) 20 (17.5–20) 0.128 Daily delivered calories, kcal/kg/day 16.7 (10.2–22.9) 16.9 (11.1–22.7) 11.1 (8.3–25.9) 0.046 15 (9.3–22.3) 14.5 (8.8–18.8) 24.1 (18.7–25.5) 0.002 Energy intake of EN in 72 h, median [IQR], kcal/kg/day 1.7 (0-7.7) 1.5 (0-7.8) 2.8 (0-7.4) 0.641 0 (0-4.8) 0 (0-4.8) 0 (2-4.1) 0.872 Energy intake of PN in 72 h, median [IQR], kcal/kg/day 11.4 (5.6–19.3) 11.8 (6.0-19.2) 8.3 (2.0-21.8) 0.272 11.1 (5.6–18.6) 10.0 (5.6–15.4) 22.9 (16.6–25.1) 0.002 Tube feeding route 0.932 0.431 Prepyloric 236 (86.8) 198 (86.8) 38 (86.4) 76 (85.4) 65 (86.7) 11 (78.6) Postpyloric 36 (13.2) 30 (13.2) 6 (13.2) 13 (14.6) 10 (13.3) 3 (21.4) LOS in ICU, day 11 ( 8 – 21 ) 11.5 ( 8 – 22 ) 10 ( 6 – 16 ) 0.124 11 ( 8 – 21 ) 11 ( 7 – 20 ) 17 ( 9 – 26 ) 0.099 Hospital acquired infection 101 (37.3) 85 (37.4) 16 (36.4) 0.892 37 (41.6) 28 (37.3) 9 (64.3) 0.060 BMI, Body mass index; APACHE II, Acute physiology and chronic health evaluation II; SOFA, Sequential organ failure assessment; AGI, Acute gastrointestinal injury; EN, Enteral nutrition; IQR, interquartile range. Data presented as mean ± standard deviation, median (IQR) or n (%). a indicated within 24 hours of admission to the ICU. 3.2 The association between the daily delivered calories and 28-day mortality 3.2.1 Normal BMI subgroup When the daily delivered calories were examined as a continuous variable in relation to 28-day mortality, a significantly non-linear pattern was demonstrated in normal BMI subgroup ( P = 0.003) which resulted in a U-shaped curve (Fig. 3 A), with significant association with 28-day mortality ( P = 0.002). The lowest mortality was noted at daily delivered calories (the minimum point of the U-shaped curve). Increasing the daily delivered calories from 0 to 18 kcal/kg/day (About 70% of the nutritional target) was associated with decreasing mortality (hazard ratio (HR) 0.892, 95% CI 0.816–0.975), while the daily delivered calories > 18 kcal/kg/day was associated with increasing mortality (HR 1.116, 95% CI 1.016–1.227)) In the normal BMI subgroup, an association was observed between APACHE II score, SOFA score, mNUTRIC score, AGI grade, mechanical ventilation, daily delivered calories, and 28-day mortality (Table 1 ). Given the collinearity among covariates, the SOFA score and mNUTRIC score were excluded from the multivariable Cox regression model due to their collinearity with the APACHE II score. Therefore, the final Cox model included APACHE II score, AGI grade, mechanical ventilation, and daily delivered calories to assess the nonlinear relationship and the robustness of the association between daily delivered calories and the HR for 28-day mortality (Table 2). We found that, after adjusting for covariates, the nonlinear relationship ( P = 0.002) and association ( P = 0.001) between daily delivered calories and HR for 28-day mortality remained robust (Fig. 4 A). 3.2.2 Overweight subgroup In the overweight subgroup, an increase in daily delivered calories was associated with an increased 28-day mortality (HR 1.124, 95% CI 1.043–1.211, P = 0.003). No non-linear relationship was found between daily delivered calories and 28-day mortality ( P = 0.466). Daily delivered calories > 15 kcal/kg/day (About 60% of the nutritional target) was associated with an HR > 1. Increasing daily delivered calories from 15 to 25 kcal/kg/day was associated with increased mortality (HR 1.160, 95% CI 1.030–1.306) (Fig. 3 B). In the overweight subgroup, an association was observed between APACHE II score, SOFA score, daily delivered calories, energy intake of PN in 72 hours, and 28-day mortality. In the multivariable Cox regression model, SOFA score and energy intake of PN in 72 hours were excluded due to their collinearity with APACHE II score and daily delivered calories, respectively. Therefore, the final Cox model included APACHE II score, AGI grade and daily delivered calories (Table 3 ). We found that, after adjusting for covariates, the association between daily delivered calories and the HR for 28-day mortality ( P = 0.004) remained robust, and no nonlinear relationship was found between the two ( P = 0.312) (Fig. 4 B). Table 2 Multivariate predictors of 28-day mortality in the normal BMI subgroup. Variable OR (95% CI) P Value APACHE II score 1.104 (1.056 - 1.154) < 0.001 AGI grade 1.279 (0.919 - 1.779) 0.145 Mechanical ventilation 2.599 (1.146 - 5.893) 0.022 Daily delivered calories 0.961 (0.923 - 1.001) 0.057 Abbreviations: BMI, body mass index; APACHE, Acute Physiology and Chronic Health Evaluation; AGI, acute gastrointestinal injury. Table 3 Multivariate predictors of 28-day mortality in the overweight subgroup. Variable OR (95% CI) P Value APACHE II score 1.108 (1.033 - 1.189) 0.004 AGI grade 2.379 (1.250 - 4.528) 0.008 Daily delivered calories 1.161 (1.060 - 1.272) 0.001 Abbreviations: APACHE, Acute Physiology and Chronic Health Evaluation; AGI, acute gastrointestinal injury. 4. Discussion In the post-hoc analysis of this prospective multicenter observational study, we found a significant non-linear association between the average daily delivered calories in the first 72 hours after ICU admission and 28-day mortality in the normal BMI subgroup, showing a \"U-shaped curve\" for calorie supply. As daily delivered calories increased from 0 to around 18 kcal/kg/day, it was associated with lower mortality; however, increases above this point were associated with higher mortality. In the overweight subgroup, we did not observe a similar non-linear relationship between daily delivered calories and mortality. Instead, higher daily delivered calories were associated with increased 28-day mortality. The guidelines from ASPEN/SCCM have conducted meta-analyses of randomized controlled trials and concluded that the dosage of energy intake does not significantly impact clinical outcomes, including mortality (20). However, evidence is mainly from studies comparing different EN dosages, demonstrating that aggressive EN does not benefit critically ill patients (21, 22). Although evidence suggests that the dosage of nutrition support, rather than the route of delivery, plays a more significant role in the outcomes of critically ill patients (23), early EN in 48 hours may have a detrimental effect (24), especially for patients with AGI (25). In such cases, the use of PN or supplement PN (SPN) may compensate for the lack of EN supply. Doig et al found that providing PN within 24 hours of ICU admission to critically ill patients might be beneficial (26), and subsequent studies have demonstrated that the harm of PN is dose-dependent rather than PN itself (27). Zusman et al. were the first to observe the \"U-shaped curve\" of calorie delivery, suggesting that an average daily calorie intake of around 70% may be optimal, while both excessive and insufficient calorie delivery could be harmful (4). This intriguing phenomenon can be explained by the risks of malnutrition and overfeeding. During the acute phase of critical illness, mitochondrial dysfunction occurs (7, 28), and overfeeding increases the metabolic burden while inhibiting beneficial metabolic processes such as ketosis and autophagy (5, 29, 30, 31). Therefore, the harmful effects of overfeeding may be widespread. On the other hand, inadequate nutrition can lead to malnutrition, which in turn brings a range of adverse effects. For overweight or obese patients, endogenous energy reserves are relatively larger, allowing them to better cope with insufficient nutritional supply. This theory seems to resemble the \"obesity paradox (32, 33).\" Our research findings also support this hypothesis. We validated the U-shaped curve of calorie delivery in the normal BMI subgroup, which is similar to the results of Zusman et al. (4) While their study focused on daily calorie delivery during the ICU stay, our study concentrated on daily calorie delivery during the first 72 hours after ICU admission, as we believe that early nutritional support during the acute phase is more crucial and has a greater impact on prognosis. Another aim of our study was to question whether a U-shaped relationship in calorie delivery also exists for patients with BMI > 25 kg/m 2 . Our results suggest that insufficient calorie delivery in the overweight subgroup during the early phase did not lead to higher mortality, which we hypothesise may be explained by their greater nutritional reserves. However, excessive nutritional delivery was strongly associated with higher mortality, possibly because these additional supplies act as a \"sweet burden\" that the patients do not actually need (32, 34). This study has several key strengths: 1. It is the first to propose that the U-shaped relationship between calorie delivery and mortality does not apply to all critically ill patients. Moreover, by conducting subgroup analysis based on patients' BMI, we validated our initial hypothesis (that the U-shaped curve only applies to patients with normal BMI), which represents the most innovative aspect of this paper. 2. The results of this study are reliable as they remained robust even after adjusting for confounding factors. 3. This study, to some extent, supports the advancement of personalized nutrition strategies for critically ill patients, presenting an exploratory hypothesis that can provide valuable reference for future research on the U-shaped relationship between nutritional delivery and outcomes. There are some limitations to this study. Firstly, although this is a post-hoc analysis of a prospective, multicenter observational study involving 12 teaching hospitals in China, the sample size remains relatively small. Therefore, the results should be considered exploratory, and larger datasets are needed to validate these findings. Secondly, only AGI patients were included in this study, not all critically ill patients. However, AGI patients are representative of patients who should be considered for nutrition support with EN combined with PN to meet their energy requirements, which makes this population appropriate for a study on the intensity of PN-led nutrition support. While we believe that our conclusions are valid regardless of whether the patients have AGI, further validation is needed to determine if the findings apply to all critically ill patients. Thirdly, the calculation of reference body weight for overweight individuals has not been definitively established. In this study, we adopted the method recommended by the guideline, but further research is needed to determine its broader applicability (35). Due to the limited number of cases, this study did not include patients with BMIs ranging greater than 30 kg/m² or less than 18.5kg /m². Additionally, BMI does not fully reflect body composition distribution, and further research is needed to explore differing values in nutritional support (35). Fourthly, there is significant heterogeneity in critically ill patients, and the associations between various factors and the presence of nutritional support remain unclear (36). These uncertainties may have an impact on the findings of this study. Fifthly, the study did not investigate the impact of protein intake, which could affect the research conclusions. Sixthly, we only explored subgroup analysis based on BMI, as we believe it is closely related to nutritional reserves. Whether other types of critically ill patients also follow the \"U-shaped curve\" of calorie delivery still requires further investigation, as this is crucial for individualized nutritional therapy in critically ill patients. 5. Conclusion In our post-hoc analysis of a prospective observational study we found the U-shaped relationship between daily delivered calories within the first 72 hours of ICU admission and 28-day mortality in critically ill patients applies only to those with BMI < 25 kg/m², and no such U-shaped curve was observed in patients with BMI > 25 kg/m². Further research is still needed to validate this conclusion. Abbreviations AGI Acute gastrointestinal injury APACHE II Acute physiology and chronic health evaluation II ASPEN American Society for parenteral and enteral nutrition BMI Body mass index CI Confidence interval EN Enteral nutrition ESICM European Society of Intensive Care Medicine HR Hazard ratio ICU Intensive care unit IBW Ideal body weight IQR Interquartile range LOS Length of stay MV Mechanical ventilation PN Parenteral nutrition SCCM Society of critical care medicine Declarations Author contributions YQW and HXL conceived the study question, contributed to the study design, data analysis and interpretation, and wrote the manuscript. CYZ, LLB and YF collected the data. YQW LK and YJW contributed to statistical analysis. YQW and DZ contributed to the study design, supervision of data collection, data analysis and interpretation. Acknowledgements Not applicable Funding This work was supported by a grant from the Natural Science Foundation of Jilin Province, China (Grand No. YDZJ202201ZYTS015). Ethics statement The study was conducted with approval from the ethics committee of the First Hospital of Jilin University in December 2012 (NO. 2012-088) and written consent has been obtained from all patients/participants. Conflict of Interest The authors declare that they have no competing interests. Acknowledgments Thanks to Professor Lu Ke and the Chinese Critical Care Nutrition Trials Group (CCCNTG) for their help in the statistical analysis of this study. We also express our gratitude to the core facility and the Bioinformatics Laboratory of The First Hospital of Jilin University for their training and generous sharing of experiences and codes. Special thanks to Professor Ruihong Wu for her guidance in statistical analysis. 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Association between early nutrition support and 28-day mortality in critically ill patients: the FRANS prospective nutrition cohort study. Crit Care. 2023;27(1):7. Zhang D, Li H, Li Y, Qu L. Gut rest strategy and trophic feeding in the acute phase of critical illness with acute gastrointestinal injury. Nutr Res Rev. 2019;32(2):176–82. Doig GS, Simpson F, Sweetman EA, Finfer SR, Cooper DJ, Heighes PT, et al. Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition: a randomized controlled trial. JAMA. 2013;309(20):2130–8. Casaer MP, Wilmer A, Hermans G, Wouters PJ, Mesotten D, Van den Berghe G. Role of disease and macronutrient dose in the randomized controlled EPaNIC trial: a post hoc analysis. Am J Respir Crit Care Med. 2013;187(3):247–55. Supinski GS, Schroder EA, Callahan LA. Mitochondria and Critical Illness. Chest. 2020;157(2):310–22. van Zanten ARH, De Waele E, Wischmeyer PE. Nutrition therapy and critical illness: practical guidance for the ICU, post-ICU, and long-term convalescence phases. Crit Care. 2019;23(1):368. de Man AME, Gunst J, Reintam Blaser A. Nutrition in the intensive care unit: from the acute phase to beyond. Intensive Care Med. 2024;50(7):1035–48. Wang Y, Li Y, Li Y, Li H, Zhang D. Enteral feeding strategies in patients with acute gastrointestinal injury: From limited to progressive to open feeding. Nutrition. 2023;117:112255. Schetz M, De Jong A, Deane AM, Druml W, Hemelaar P, Pelosi P, et al. Obesity in the critically ill: a narrative review. Intensive Care Med. 2019;45(6):757–69. Shapiro ML, Komisarow J. The Obesity Paradox and Effects of Early Nutrition: Is There a Paradox, or Is There Not? Crit Care Med. 2017;45(5):918–9. Dickerson RN, Andromalos L, Brown JC, Correia M, Pritts W, Ridley EJ, et al. Obesity and critical care nutrition: current practice gaps and directions for future research. Crit Care. 2022;26(1):283. Singer P, Blaser AR, Berger MM, Alhazzani W, Calder PC, Casaer MP, et al. ESPEN guideline on clinical nutrition in the intensive care unit. Clin Nutr. 2019;38(1):48–79. Moonen HPFX, Beckers KJH, van Zanten ARH. Energy expenditure and indirect calorimetry in critical illness and convalescence: current evidence and practical considerations. J Intensive Care. 2021;9(1):8. Additional Declarations No competing interests reported. Supplementary Files Supplementarydocument.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-6005098\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":414754384,\"identity\":\"e720d4e3-fc4c-45b6-9754-014a2eb92ee7\",\"order_by\":0,\"name\":\"Youquan Wang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"First Hospital of Jilin University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Youquan\",\"middleName\":\"\",\"lastName\":\"Wang\",\"suffix\":\"\"},{\"id\":414754385,\"identity\":\"4c7a1c56-fc9f-4c4f-acff-eaa4733fd105\",\"order_by\":1,\"name\":\"Yanjuan Wang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"First Hospital of Jilin University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yanjuan\",\"middleName\":\"\",\"lastName\":\"Wang\",\"suffix\":\"\"},{\"id\":414754386,\"identity\":\"bf30960c-dfef-4c99-801c-c1d54daf6c0f\",\"order_by\":2,\"name\":\"Yao Fu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"First Hospital of Jilin University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yao\",\"middleName\":\"\",\"lastName\":\"Fu\",\"suffix\":\"\"},{\"id\":414754387,\"identity\":\"b39d6a95-2b36-4ebf-9297-83b2e04ee53c\",\"order_by\":3,\"name\":\"Lingling Bao\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"First Hospital of Jilin University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Lingling\",\"middleName\":\"\",\"lastName\":\"Bao\",\"suffix\":\"\"},{\"id\":414754389,\"identity\":\"7566477c-a367-4909-a6b2-7acfc4099e26\",\"order_by\":4,\"name\":\"Dong Zhang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"First Hospital of Jilin University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Dong\",\"middleName\":\"\",\"lastName\":\"Zhang\",\"suffix\":\"\"},{\"id\":414754392,\"identity\":\"e5b157c0-9a5e-46b7-a738-771dbf115b2f\",\"order_by\":5,\"name\":\"H Li\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsElEQVRIiWNgGAWjYBACPmYGNgaGCjYZEEeCKC1sYC1n2HhI0AJCjG0MpGhhZ2B7zDuPj8fgAPPB2zwMdnnEOIzdcOY2NqAWtmRrHobkYmK0sEl8BGvhMZPmYTiQ2ECUlsQ5IC3830jQ8rEBbAsb8VokZxxj45E8zGZsOccgmbAWfv4DQMNrjsnxHW9+eONNhR1hLUBNH4DEMQYGZhDHgLB6GKghXukoGAWjYBSMPAAAhVApSlI7+GsAAAAASUVORK5CYII=\",\"orcid\":\"\",\"institution\":\"First Hospital of Jilin University\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"H\",\"middleName\":\"\",\"lastName\":\"Li\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-02-11 08:08:36\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-6005098/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-6005098/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":76298336,\"identity\":\"483a4760-6f27-4ed2-b027-1bd1399bfc0e\",\"added_by\":\"auto\",\"created_at\":\"2025-02-14 13:37:41\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":92504,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003ePatient inclusion flow chart.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Onlinefloatimage1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6005098/v1/59743ac988477aa5790d6d11.png\"},{\"id\":76297698,\"identity\":\"053a8c6a-0ecc-40d1-b857-e609a33ef4cc\",\"added_by\":\"auto\",\"created_at\":\"2025-02-14 13:29:41\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":306961,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eAssociation between daily delivered calories and 28-day mortality in all patients.\\u003c/p\\u003e\\n\\u003cp\\u003eThe U-shaped curve corresponds to the Y axis on the left, indicating a non-linear relationship between daily calorie delivery and 28-day mortality. The histogram corresponds to the right Y-axis and represents the distribution of daily delivered calories in different subgroups (BMI \\u0026lt; 25 kg/m\\u003csup\\u003e2\\u003c/sup\\u003e or not)\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6005098/v1/f77f7dca6d85f20733048d6b.png\"},{\"id\":76297697,\"identity\":\"32c206a9-99c3-4bce-8b16-76cb6422fc9f\",\"added_by\":\"auto\",\"created_at\":\"2025-02-14 13:29:41\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":150221,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eAssociation between daily delivered calories and HR for 28-day mortality in normal BMI subgroup (A) and overweight subgroup (B).\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage3.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6005098/v1/13451086bbd7506275356a29.png\"},{\"id\":76297709,\"identity\":\"a634c5e0-9cd9-4aa7-8cc0-9fd84eaef50b\",\"added_by\":\"auto\",\"created_at\":\"2025-02-14 13:29:42\",\"extension\":\"png\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":344713,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eAssociation between daily delivered calories and adjusted HR for 28-day mortality in normal BMI subgroup (A) and overweight subgroup (B).\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage4.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6005098/v1/8581feb67e63794694f00712.png\"},{\"id\":76806876,\"identity\":\"2a249e3e-8fff-4dbd-a9ce-957d6a7b5bab\",\"added_by\":\"auto\",\"created_at\":\"2025-02-21 03:16:55\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":1986694,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6005098/v1/87640392-1a9b-419a-ade1-00d50994cd64.pdf\"},{\"id\":76297695,\"identity\":\"2897a367-ab6b-4d89-8b65-b7de2c69e981\",\"added_by\":\"auto\",\"created_at\":\"2025-02-14 13:29:41\",\"extension\":\"docx\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":30843,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"Supplementarydocument.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6005098/v1/6919dd2a98d888fe459b8087.docx\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"The U-shaped Curve of Energy Supply in the First 72 Hours of Critical Illness May Apply Only to Patients with Normal Body Mass Index: A Post-hoc Analysis of a Prospective Observational Multicenter Study\",\"fulltext\":[{\"header\":\"1. Introduction\",\"content\":\"\\u003cp\\u003eMalnutrition is prevalent among critically ill patients, particularly those who are admitted to the intensive care unit (ICU). This is frequently attributed to inadequate nutrition prior to ICU admission and the profound hyper-catabolic state induced by conditions such as sepsis and trauma, as outlined in the European Society of Intensive Care Medicine's (ESICM) guidelines (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e). This leads to immune impairment, increased infection susceptibility, compromised healing, and ultimately higher mortality rates in critically ill patients (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003eNutritional support plays a crucial role in managing critically ill patients and can be administered through enteral feeding or parenteral feeding. Parenteral nutrition (PN) is employed when enteral nutrition (EN) is inadequate or not feasible. However, the optimal dosage of nutritional support during the early phase of critical illness remains controversial (\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e). Zusman et al. first revealed the \\\"U-shaped curve\\\" of calorie supply in critically ill patients through retrospective studies (\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e), indicating that both insufficient and excessive calorie supply are detrimental. The most beneficial energy supply may be one that reaches about 70% of the resting energy expenditure on average per day. Overfeeding can impose a digestive burden, suppress beneficial metabolic processes such as autophagy and ketosis, and may also lead to \\\"hibernating mitochondria to die of overwork (\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e).\\\" This theory explains the existence of the \\\"U-shaped curve,\\\" showing that higher nutritional supply is not always better. The subsequent PROTINVENT study also suggests that protein supply, like calories, may follow a \\\"U-shaped curve,\\\" with both excessive and insufficient protein intake being associated with poor prognosis in critically ill patients (\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e). Gradual feeding may be optimal, aligning with the feeding strategies recommended by the ESPEN guidelines (\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003eHowever, the harm caused by inadequate feeding may vary for each patient. During the acute phase of critical illness, the body is in a state of high catabolism (\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e), and patients with poor nutritional reserves may require more nutritional support, whereas the harm of inadequate feeding may be less significant for those with better nutritional reserves (\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e). Body mass index (BMI) may, to some extent, represent nutritional reserves (\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e). Therefore, we hypothesize that the \\\"U-shaped curve\\\" of energy supply applies only to patients with a normal BMI, but not to those with a BMI greater than 25 kg/m\\u0026sup2;.\\u003c/p\\u003e\"},{\"header\":\"2. Methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.1 Participants\\u003c/h2\\u003e \\u003cp\\u003eWe used data from a prospective, observational, nationwide study conducted between September 2014 and December 2014 in China to investigate the association of nutrition support with prognosis in critically ill patients with acute gastrointestinal injury (AGI) \\u003csup\\u003e(\\u003c/sup\\u003e14\\u003csup\\u003e)\\u003c/sup\\u003e. The names and geographical locations of the 12 teaching hospitals are in the Supplementary document. The project protocols followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines (\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e). Patients meeting the ESICM's definition and grading system for AGI were eligible for inclusion if they also received nutrition support within 72 hours of admission (\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e). Individuals with severe cardiovascular disease, post-cardiac arrest, chronic end-stage organ failure, malignancy, Crohn\\u0026rsquo;s disease, ulcerative colitis, or short bowel syndrome, as well as those who died within 72 hours or were hospitalized for less than 72 hours before AGI was diagnosed, were excluded from this study. The study was conducted with approval from the ethics committee of the First Hospital of Jilin University in December 2012 (NO. 2012-088).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.2 Data collection\\u003c/h2\\u003e \\u003cp\\u003eThe enrolled patients were categorized into subgroups based on the BMI cut-off values from previous studies (\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e), with one subgroup being the normal BMI (18.5\\u0026thinsp;\\u0026le;\\u0026thinsp;BMI\\u0026thinsp;\\u0026lt;\\u0026thinsp;25 kg/m\\u0026sup2;) and the other subgroup being the overweight (BMI\\u0026thinsp;\\u0026ge;\\u0026thinsp;25 kg/m\\u0026sup2;). For individuals with a BMI\\u0026thinsp;\\u0026lt;\\u0026thinsp;25 kg/m\\u0026sup2;, actual body weight (ABW) was used to determine energy requirements. Moreover, for those with a BMI\\u0026thinsp;\\u0026ge;\\u0026thinsp;25 kg/m\\u0026sup2;, the reference (adjusted) body weight was replaced with the ideal body weight (IBW). The IBW was calculated by subtracting 100 (for males) or 106 (for females) from 0.9 multiplied by the height in centimeters. Additionally, when calculating energy requirements, it was considered to include 20% of the excess weight (the difference between the ABW and IBW) in addition to the IBW (\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e). The nutritional EN and PN supply information of patients in the first 72 hours of ICU admission were collected. And collected data also included general demographics, primary diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE II) score, AGI grade, and 28-day mortality. These parameters were used for comprehensive analysis and evaluation. Data was thoroughly screened for missing information and any implausible or outlier values.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.3 Statistical analyses\\u003c/h2\\u003e \\u003cp\\u003eContinuous variables were expressed as means and standard deviations for normally distributed variables using the t-test. The median and interquartile range (IQR) were reported for non-normally distributed variables, and the Kruskal-Wallis test was employed for evaluation. Categorical variables were compared using the Chi-squared test.\\u003c/p\\u003e \\u003cp\\u003eWe performed a subgroup analysis based on whether the patients had a BMI\\u0026thinsp;\\u0026gt;\\u0026thinsp;25kg/m\\u003csup\\u003e2\\u003c/sup\\u003e. Initially an unadjusted Cox proportional hazards model for 28-day mortality was used, with the daily delivered calories entered as a continuous variable. Since the effects of daily delivered calories were considered to be non-linear, the percent was modeled as a restricted cubic spline with pre-specified knots. Subsequently, the Cox regression results were adjusted for potential risk factors affecting mortality in different subgroups to explore the association and non-linear relationship between daily delivered calories and the adjusted hazard ratio (HR) for 28-day mortality. Non-linearity was tested by ANOVA. An adjusted model with covariates selected based on univariate analysis. Multicollinearity was assessed by variation inflation factors and R\\u003csup\\u003e2\\u003c/sup\\u003e. A \\u003cem\\u003eP\\u003c/em\\u003e value\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05 was considered significant.\\u003c/p\\u003e \\u003cp\\u003eThe statistical analysis was carried out using SPSS for Mac version 26(SPSS Inc, Chicago, IL, USA) and Rv4.3.1(R Foundation for Statistical Computing, Vienna, Austria) using RStudio v1.0.136 (RStudio Inc, Boston, MA, USA)\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"3. Results\",\"content\":\"\\u003cdiv id=\\\"Sec7\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e3.1 Baseline characteristics\\u003c/h2\\u003e \\u003cp\\u003eA total of 443 patients were initially enrolled, but 64 individuals were excluded from the analysis due to missing nutrition data or AGI grade, treatment abandoning, or a hospitalization duration of less than 72 hours. Due to the small sample sizes with underweight (BMI\\u0026thinsp;\\u0026lt;\\u0026thinsp;18.5 kg/m\\u0026sup2;) (10 individuals) and obese (BMI\\u0026thinsp;\\u0026ge;\\u0026thinsp;30 kg/m\\u0026sup2;) (8 individuals), they were excluded from the final analysis for robust statistical purposes.\\u003c/p\\u003e \\u003cp\\u003eThe final sample size for analysis included 361 patients who met all the inclusion criteria. All patients were divided into two subgroups according to their BMI, with 272 patients (75.3%) in the normal BMI subgroup, and 89 patients (24.7%) in the overweight subgroup (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e and Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). The daily average delivered calories over the first 72 hours in the normal BMI subgroup and the overweight subgroup is shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e.\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eClinical and demographic data for development and validation cohort.\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"10\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c6\\\" colnum=\\\"6\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c7\\\" colnum=\\\"7\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c8\\\" colnum=\\\"8\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c9\\\" colnum=\\\"9\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c10\\\" colnum=\\\"10\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eVariables\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"4\\\" nameend=\\\"c5\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003eNormal BMI subgroup\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c6\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"4\\\" nameend=\\\"c10\\\" namest=\\\"c7\\\"\\u003e \\u003cp\\u003eOverweight subgroup\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eTotal (n\\u0026thinsp;=\\u0026thinsp;272)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eSurvived (n\\u0026thinsp;=\\u0026thinsp;228)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eDied within 28 days (n\\u0026thinsp;=\\u0026thinsp;44)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e value\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eTotal (n\\u0026thinsp;=\\u0026thinsp;89)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003eSurvived (n\\u0026thinsp;=\\u0026thinsp;75)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003eDied within 28 days (n\\u0026thinsp;=\\u0026thinsp;14)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e value\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAge, y\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e61.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;18.7\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e61.5\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;18.0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e63.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;22.1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.443\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\" morerows=\\\"20\\\" rowspan=\\\"21\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e57.6\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;18.1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e56.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;17.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e62.1\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;20.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003e0.309\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eGender\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMale\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e183 (67.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e154 (67.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e29 (65.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.832\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e59 (66.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e50 (66.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e9 (64.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c10\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.863\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eFemale\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e89 (22.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e74 (32.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e16 (34.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e30 (33.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e25 (33.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e5 (35.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eBMI\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e22.6\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e22.7\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e22.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.7\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.098\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e26.7\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.2\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e26.5\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e27.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003e0.078\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePrimary diagnosis\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.514\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003e0.101\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNeurologic\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e55 (20.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e47 (20.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e8 (18.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e16 (18.0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e10 (13.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e6 (42.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCirculatory\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e18 (6.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e16 (7.0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e2 (4.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e5 (5.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e4 (5.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e1 (7.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eRespiratory\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e116 (42.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e99 (43.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e17 (38.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e46 (51.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e41 (54.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e5 (35.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMulti trauma\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e18 (6.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e16 (7.0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e2 (4.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e5 (5.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e5 (6.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e0 (0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eOthers\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e65 (23.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e50 (21.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e15 (34.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e17 (19.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e15 (20.0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e2 (14.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSeverity of illness \\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd 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colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eHypertension\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e137 (50.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e118 (51.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e19 (43.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.298\\u003c/p\\u003e 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\\u003cp\\u003e14 (31.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.990\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e26 (29.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e21 (28.0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e5 (35.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003e0.560\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePrimary AGI\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e143 (52.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e119 (52.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e24 (54.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.775\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e35 (39.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e28 (37.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e7 (50.0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003e0.373\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMechanical ventilation\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e181 (66.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e144 (63.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e37 (84.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.007\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e56 (62.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e45 (60.0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e11 (78.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003e0.187\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSepsis\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e115 (42.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e97 (42.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e18 (40.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.869\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e37 (41.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e29 (38.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e8 (57.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003e0.198\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eEN start time, h\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e48 (24\\u0026ndash;72)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e48 (24\\u0026ndash;72)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e48 (24\\u0026ndash;72)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.795\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e48 (24\\u0026ndash;72)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e48 (24\\u0026ndash;72)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e48 (24\\u0026ndash;54)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003e0.765\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eEN initial rate, ml/h\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e20 (\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e20 (\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e20 (\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.946\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e20 (\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e20 (\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e20 (17.5\\u0026ndash;20)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003e0.128\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDaily delivered calories, kcal/kg/day\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e16.7 (10.2\\u0026ndash;22.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e16.9 (11.1\\u0026ndash;22.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e11.1 (8.3\\u0026ndash;25.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.046\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e15 (9.3\\u0026ndash;22.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e14.5 (8.8\\u0026ndash;18.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e24.1 (18.7\\u0026ndash;25.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003e0.002\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eEnergy intake of EN in 72 h, median [IQR], kcal/kg/day\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.7 (0-7.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.5 (0-7.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e2.8 (0-7.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.641\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0 (0-4.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e0 (0-4.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e0 (2-4.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003e0.872\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eEnergy intake of PN in 72 h, median [IQR], kcal/kg/day\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e11.4 (5.6\\u0026ndash;19.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e11.8 (6.0-19.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e8.3 (2.0-21.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.272\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e11.1 (5.6\\u0026ndash;18.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e10.0 (5.6\\u0026ndash;15.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e22.9 (16.6\\u0026ndash;25.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003e0.002\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eTube feeding route\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.932\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003e0.431\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePrepyloric\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e236 (86.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e198 (86.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e38 (86.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e76 (85.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e65 (86.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e11 (78.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePostpyloric\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e36 (13.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e30 (13.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e6 (13.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e13 (14.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e10 (13.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e3 (21.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eLOS in ICU, day\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e11 (\\u003cspan additionalcitationids=\\\"CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20\\\" citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e11.5 (\\u003cspan additionalcitationids=\\\"CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21\\\" citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e10 (\\u003cspan additionalcitationids=\\\"CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15\\\" citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.124\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e11 (\\u003cspan additionalcitationids=\\\"CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20\\\" citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e11 (\\u003cspan additionalcitationids=\\\"CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19\\\" citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e17 (\\u003cspan additionalcitationids=\\\"CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25\\\" citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR26\\\" class=\\\"CitationRef\\\"\\u003e26\\u003c/span\\u003e)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003e0.099\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eHospital acquired infection\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e101 (37.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e85 (37.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e16 (36.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.892\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e37 (41.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e28 (37.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e \\u003cp\\u003e9 (64.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c10\\\"\\u003e \\u003cp\\u003e0.060\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eBMI, Body mass index; APACHE II, Acute physiology and chronic health evaluation II; SOFA, Sequential organ failure assessment; AGI, Acute gastrointestinal injury; EN, Enteral nutrition; IQR, interquartile range. Data presented as mean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;standard deviation, median (IQR) or n (%).\\u003c/p\\u003e \\u003cp\\u003e \\u003csup\\u003ea\\u003c/sup\\u003e indicated within 24 hours of admission to the ICU.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec8\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e3.2 The association between the daily delivered calories and 28-day mortality\\u003c/h2\\u003e \\u003cdiv id=\\\"Sec9\\\" class=\\\"Section3\\\"\\u003e \\u003ch2\\u003e3.2.1 Normal BMI subgroup\\u003c/h2\\u003e \\u003cp\\u003eWhen the daily delivered calories were examined as a continuous variable in relation to 28-day mortality, a significantly non-linear pattern was demonstrated in normal BMI subgroup (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.003) which resulted in a U-shaped curve (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003eA), with significant association with 28-day mortality (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.002). The lowest mortality was noted at daily delivered calories (the minimum point of the U-shaped curve). Increasing the daily delivered calories from 0 to 18 kcal/kg/day (About 70% of the nutritional target) was associated with decreasing mortality (hazard ratio (HR) 0.892, 95% CI 0.816\\u0026ndash;0.975), while the daily delivered calories\\u0026thinsp;\\u0026gt;\\u0026thinsp;18 kcal/kg/day was associated with increasing mortality (HR 1.116, 95% CI 1.016\\u0026ndash;1.227))\\u003c/p\\u003e \\u003cp\\u003eIn the normal BMI subgroup, an association was observed between APACHE II score, SOFA score, mNUTRIC score, AGI grade, mechanical ventilation, daily delivered calories, and 28-day mortality (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). Given the collinearity among covariates, the SOFA score and mNUTRIC score were excluded from the multivariable Cox regression model due to their collinearity with the APACHE II score. Therefore, the final Cox model included APACHE II score, AGI grade, mechanical ventilation, and daily delivered calories to assess the nonlinear relationship and the robustness of the association between daily delivered calories and the HR for 28-day mortality (Table\\u0026nbsp;2). We found that, after adjusting for covariates, the nonlinear relationship (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.002) and association (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.001) between daily delivered calories and HR for 28-day mortality remained robust (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003eA).\\u003c/p\\u003e\\u003c/div\\u003e \\u003cdiv id=\\\"Sec10\\\" class=\\\"Section3\\\"\\u003e \\u003ch2\\u003e3.2.2 Overweight subgroup\\u003c/h2\\u003e \\u003cp\\u003eIn the overweight subgroup, an increase in daily delivered calories was associated with an increased 28-day mortality (HR 1.124, 95% CI 1.043\\u0026ndash;1.211, \\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.003). No non-linear relationship was found between daily delivered calories and 28-day mortality (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.466). Daily delivered calories\\u0026thinsp;\\u0026gt;\\u0026thinsp;15 kcal/kg/day (About 60% of the nutritional target) was associated with an HR\\u0026thinsp;\\u0026gt;\\u0026thinsp;1. Increasing daily delivered calories from 15 to 25 kcal/kg/day was associated with increased mortality (HR 1.160, 95% CI 1.030\\u0026ndash;1.306) (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003eB).\\u003c/p\\u003e \\u003cp\\u003eIn the overweight subgroup, an association was observed between APACHE II score, SOFA score, daily delivered calories, energy intake of PN in 72 hours, and 28-day mortality. In the multivariable Cox regression model, SOFA score and energy intake of PN in 72 hours were excluded due to their collinearity with APACHE II score and daily delivered calories, respectively. Therefore, the final Cox model included APACHE II score, AGI grade and daily delivered calories (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e). We found that, after adjusting for covariates, the association between daily delivered calories and the HR for 28-day mortality (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.004) remained robust, and no nonlinear relationship was found between the two (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.312) (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003eB).\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eTable 2\\u0026nbsp;\\u003c/strong\\u003eMultivariate predictors of 28-day mortality in the normal BMI subgroup.\\u003c/p\\u003e\\n\\u003ctable border=\\\"1\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"100%\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003eVariable\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cem\\u003eOR\\u003c/em\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22px;\\\"\\u003e\\n \\u003cp\\u003e(95%\\u003cem\\u003eCI)\\u003c/em\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cem\\u003eP Value\\u003c/em\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003eAPACHE II score\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e1.104\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22px;\\\"\\u003e\\n \\u003cp\\u003e(1.056 - 1.154)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt; 0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003eAGI grade\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e1.279\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22px;\\\"\\u003e\\n \\u003cp\\u003e(0.919 - 1.779)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e0.145\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003eMechanical ventilation\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e2.599\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22px;\\\"\\u003e\\n \\u003cp\\u003e(1.146 - 5.893)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e0.022\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003eDaily delivered calories\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e0.961\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22px;\\\"\\u003e\\n \\u003cp\\u003e(0.923 - 1.001)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e0.057\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003eAbbreviations: BMI, body mass index; APACHE, Acute Physiology and Chronic Health Evaluation; AGI, acute gastrointestinal injury.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTable 3\\u0026nbsp;\\u003c/strong\\u003eMultivariate predictors of 28-day mortality in the\\u0026nbsp;overweight\\u0026nbsp;subgroup.\\u003c/p\\u003e\\n\\u003ctable border=\\\"1\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"100%\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003eVariable\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cem\\u003eOR\\u003c/em\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22px;\\\"\\u003e\\n \\u003cp\\u003e(95%\\u003cem\\u003eCI)\\u003c/em\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cem\\u003eP Value\\u003c/em\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003eAPACHE II score\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e1.108\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22px;\\\"\\u003e\\n \\u003cp\\u003e(1.033 - 1.189)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e0.004\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003eAGI grade\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e2.379\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22px;\\\"\\u003e\\n \\u003cp\\u003e(1.250 - 4.528)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e0.008\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 52px;\\\"\\u003e\\n \\u003cp\\u003eDaily delivered calories\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e1.161\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22px;\\\"\\u003e\\n \\u003cp\\u003e(1.060 - 1.272)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003eAbbreviations: APACHE, Acute Physiology and Chronic Health Evaluation; AGI, acute gastrointestinal injury.\\u003c/p\\u003e\"},{\"header\":\"4. Discussion\",\"content\":\"\\u003cp\\u003eIn the post-hoc analysis of this prospective multicenter observational study, we found a significant non-linear association between the average daily delivered calories in the first 72 hours after ICU admission and 28-day mortality in the normal BMI subgroup, showing a \\u0026quot;U-shaped curve\\u0026quot; for calorie supply. As daily delivered calories increased from 0 to around 18 kcal/kg/day, it was associated with lower mortality; however, increases above this point were associated with higher mortality. In the overweight subgroup, we did not observe a similar non-linear relationship between daily delivered calories and mortality. Instead, higher daily delivered calories were associated with increased 28-day mortality.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eThe guidelines from ASPEN/SCCM have conducted meta-analyses of randomized controlled trials and concluded that the dosage of energy intake does not significantly impact clinical outcomes, including mortality (20). However, evidence is mainly from studies comparing different EN dosages, demonstrating that aggressive EN does not benefit critically ill patients (21,\\u0026nbsp;22). Although evidence suggests that the dosage of nutrition support, rather than the route of delivery, plays a more significant role in the outcomes of critically ill patients (23), early EN in 48 hours may have a detrimental effect (24), especially for patients with AGI (25). In such cases, the use of PN or supplement PN (SPN) may compensate for the lack of EN supply. Doig et al found that providing PN within 24 hours of ICU admission to critically ill patients might be beneficial (26),\\u0026nbsp;and subsequent studies have demonstrated that the harm of PN is dose-dependent rather than PN itself (27).\\u003c/p\\u003e\\n\\u003cp\\u003eZusman et al. were the first to observe the \\u0026quot;U-shaped curve\\u0026quot; of calorie delivery, suggesting that an average daily calorie intake of around 70% may be optimal, while both excessive and insufficient calorie delivery could be harmful (4). This intriguing phenomenon can be explained by the risks of malnutrition and overfeeding. During the acute phase of critical illness, mitochondrial dysfunction occurs (7,\\u0026nbsp;28), and overfeeding increases the metabolic burden while inhibiting beneficial metabolic processes such as ketosis and autophagy (5,\\u0026nbsp;29,\\u0026nbsp;30,\\u0026nbsp;31). Therefore, the harmful effects of overfeeding may be widespread. On the other hand, inadequate nutrition can lead to malnutrition, which in turn brings a range of adverse effects. For overweight or obese patients, endogenous energy reserves are relatively larger, allowing them to better cope with insufficient nutritional supply. This theory seems to resemble the \\u0026quot;obesity paradox (32,\\u0026nbsp;33).\\u0026quot;\\u003c/p\\u003e\\n\\u003cp\\u003eOur research findings also support this hypothesis. We validated the U-shaped curve of calorie delivery in the normal BMI subgroup, which is similar to the results of Zusman et al. (4) While their study focused on daily calorie delivery during the ICU stay, our study concentrated on daily calorie delivery during the first 72 hours after ICU admission, as we believe that early nutritional support during the acute phase is more crucial and has a greater impact on prognosis. Another aim of our study was to question whether a U-shaped relationship in calorie delivery also exists for patients with BMI \\u0026gt; 25 kg/m\\u003csup\\u003e2\\u003c/sup\\u003e. Our results suggest that insufficient calorie delivery in the overweight subgroup during the early phase did not lead to higher mortality, which we hypothesise may be explained by their greater nutritional reserves. However, excessive nutritional delivery was strongly associated with higher mortality, possibly because these additional supplies act as a \\u0026quot;sweet burden\\u0026quot; that the patients do not actually need (32,\\u0026nbsp;34).\\u003c/p\\u003e\\n\\u003cp\\u003eThis study has several key strengths: 1. It is the first to propose that the U-shaped relationship between calorie delivery and mortality does not apply to all critically ill patients. Moreover, by conducting subgroup analysis based on patients\\u0026apos; BMI, we validated our initial hypothesis (that the U-shaped curve only applies to patients with normal BMI), which represents the most innovative aspect of this paper. 2. The results of this study are reliable as they remained robust even after adjusting for confounding factors. 3. This study, to some extent, supports the advancement of personalized nutrition strategies for critically ill patients, presenting an exploratory hypothesis that can provide valuable reference for future research on the U-shaped relationship between nutritional delivery and outcomes.\\u003c/p\\u003e\\n\\u003cp\\u003eThere are some limitations to this study. Firstly, although this is a post-hoc analysis of a prospective, multicenter observational study involving 12 teaching hospitals in China, the sample size remains relatively small. Therefore, the results should be considered exploratory, and larger datasets are needed to validate these findings. Secondly, only AGI patients were included in this study, not all critically ill patients. However, AGI patients are representative of patients who should be considered for nutrition support with EN combined with PN to meet their energy requirements, which makes this population appropriate for a study on the intensity of PN-led nutrition support. While we believe that our conclusions are valid regardless of whether the patients have AGI, further validation is needed to determine if the findings apply to all critically ill patients. Thirdly, the calculation of reference body weight for overweight individuals has not been definitively established. In this study, we adopted the method recommended by the guideline, but further research is needed to determine its broader applicability (35). Due to the limited number of cases, this study did not include patients with BMIs ranging greater than 30 kg/m\\u0026sup2; or less than 18.5kg /m\\u0026sup2;. Additionally, BMI does not fully reflect body composition distribution, and further research is needed to explore differing values in nutritional support (35). Fourthly, there is significant heterogeneity in critically ill patients, and the associations between various factors and the presence of nutritional support remain unclear (36). These uncertainties may have an impact on the findings of this study. Fifthly, the study did not investigate the impact of protein intake, which could affect the research conclusions. Sixthly, we only explored subgroup analysis based on BMI, as we believe it is closely related to nutritional reserves. Whether other types of critically ill patients also follow the \\u0026quot;U-shaped curve\\u0026quot; of calorie delivery still requires further investigation, as this is crucial for individualized nutritional therapy in critically ill patients.\\u003c/p\\u003e\"},{\"header\":\"5. Conclusion\",\"content\":\"\\u003cp\\u003eIn our post-hoc analysis of a prospective observational study we found the U-shaped relationship between daily delivered calories within the first 72 hours of ICU admission and 28-day mortality in critically ill patients applies only to those with BMI \\u0026lt; 25 kg/m\\u0026sup2;, and no such U-shaped curve was observed in patients with BMI \\u0026gt; 25 kg/m\\u0026sup2;. Further research is still needed to validate this conclusion.\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cdiv class=\\\"DefinitionList\\\"\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eAGI\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eAcute gastrointestinal injury\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eAPACHE II\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eAcute physiology and chronic health evaluation II\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eASPEN\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eAmerican Society for parenteral and enteral nutrition\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eBMI\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eBody mass index\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eCI\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eConfidence interval\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eEN\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eEnteral nutrition\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eESICM\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eEuropean Society of Intensive Care Medicine\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eHR\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eHazard ratio\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eICU\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eIntensive care unit\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eIBW\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eIdeal body weight\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eIQR\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eInterquartile range\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eLOS\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eLength of stay\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eMV\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eMechanical ventilation\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003ePN\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eParenteral nutrition\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eSCCM\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eSociety of critical care medicine\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003c/div\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eAuthor contributions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eYQW and HXL conceived the study question, contributed to the study design, data analysis and interpretation, and wrote the manuscript. CYZ, LLB and YF collected the data. YQW \\u0026nbsp;LK and YJW contributed to statistical analysis. YQW and DZ contributed to the study design, supervision of data collection, data analysis and interpretation.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNot applicable\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis work was supported by a grant from the Natural Science Foundation of Jilin Province, China (Grand No. YDZJ202201ZYTS015).\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEthics statement\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe study was conducted with approval from the ethics committee of the First Hospital of Jilin University in December 2012 (NO. 2012-088) and written consent has been obtained from all patients/participants.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConflict of Interest\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare that they have no competing interests.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgments\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThanks to Professor Lu Ke and the Chinese Critical Care Nutrition Trials Group (CCCNTG) for their help in the statistical analysis of this study. We also express our gratitude to the core facility and the Bioinformatics Laboratory of The First Hospital of Jilin University for their training and generous sharing of experiences and codes. Special thanks to Professor Ruihong Wu for her guidance in statistical analysis.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eReintam Blaser A, Malbrain ML, Starkopf J, Fruhwald S, Jakob SM, De Waele J, et al. Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems. Intensive Care Med. 2012;38(3):384\\u0026ndash;94.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eReintam Blaser A, Starkopf J, Alhazzani W, Berger MM, Casaer MP, Deane AM, et al. Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines. Intensive Care Med. 2017;43(3):380\\u0026ndash;98.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eCompher C, Bingham AL, McCall M, Patel J, Rice TW, Braunschweig C, et al. Guidelines for the provision of nutrition support therapy in the adult critically ill patient: The American Society for Parenteral and Enteral Nutrition. JPEN J Parenter Enter Nutr. 2022;46(1):12\\u0026ndash;41.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eZusman O, Theilla M, Cohen J, Kagan I, Bendavid I, Singer P. Resting energy expenditure, calorie and protein consumption in critically ill patients: a retrospective cohort study. Crit Care. 2016;20(1):367.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eGunst J, Casaer MP, Preiser JC, Reignier J, Van den Berghe G. Toward nutrition improving outcome of critically ill patients: How to interpret recent feeding RCTs? Crit Care. 2023;27(1):43.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePaoli A, Tinsley GM, Mattson MP, De Vivo I, Dhawan R, Moro T. Common and divergent molecular mechanisms of fasting and ketogenic diets. Trends Endocrinol Metab. 2024;35(2):125\\u0026ndash;41.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMoonen H, Van Zanten ARH. Mitochondrial dysfunction in critical illness during acute metabolic stress and convalescence: consequences for nutrition therapy. Curr Opin Crit Care. 2020;26(4):346\\u0026ndash;54.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKoekkoek W, van Setten CHC, Olthof LE, Kars J, van Zanten ARH. Timing of PROTein INtake and clinical outcomes of adult critically ill patients on prolonged mechanical VENTilation: The PROTINVENT retrospective study. Clin Nutr. 2019;38(2):883\\u0026ndash;90.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSinger P, Blaser AR, Berger MM, Calder PC, Casaer M, Hiesmayr M, et al. ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit. Clin Nutr. 2023;42(9):1671\\u0026ndash;89.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSinger P, Blaser AR, Berger MM. ESPEN practical and partially revised guideline: clinical nutrition in the intensive care unit. Clin Nutr. 2023;42.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eAl-Dorzi HM, Stapleton RD, Arabi YM. Nutrition priorities in obese critically ill patients. Curr Opin Clin Nutr Metab Care. 2022;25(2):99\\u0026ndash;109.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eArabi YM, Casaer MP, Chapman M, Heyland DK, Ichai C, Marik PE, et al. The intensive care medicine research agenda in nutrition and metabolism. Intensive Care Med. 2017;43(9):1239\\u0026ndash;56.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eCederholm T, Bosaeus I, Barazzoni R, Bauer J, Van Gossum A, Klek S, et al. Diagnostic criteria for malnutrition - An ESPEN Consensus Statement. Clin Nutr. 2015;34(3):335\\u0026ndash;40.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLi H, Lu J, Li H, Duan A, Wang Y, Zhang D. Association between nutrition support and acute gastrointestinal injury in critically ill patients during the first 72 hours. Clin Nutr. 2021;40(1):217\\u0026ndash;21.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eElm Ev, Altman DG, Egger M, Pocock SJ, G\\u0026oslash;tzsche PC, Vandenbroucke JP. Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ. 2007;335(7624):806\\u0026ndash;8.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eReintam Blaser A, Malbrain ML, Starkopf J, Fruhwald S, Jakob SM, De Waele J, et al. Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems. Intensive Care Med. 2012;38:384\\u0026ndash;94.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBorel AL, Schwebel C, Planquette B, V\\u0026eacute;sin A, Garrouste-Orgeas M, Adrie C, et al. Initiation of nutritional support is delayed in critically ill obese patients: a multicenter cohort study. Am J Clin Nutr. 2014;100(3):859\\u0026ndash;66.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePardo E, Lescot T, Preiser JC, Massanet P, Pons A, Jaber S, et al. Association between early nutrition support and 28-day mortality in critically ill patients: the FRANS prospective nutrition cohort study. Crit Care. 2023;27(1):7.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHarvey SE, Parrott F, Harrison DA, Bear DE, Segaran E, Beale R, et al. Trial of the route of early nutritional support in critically ill adults. N Engl J Med. 2014;371(18):1673\\u0026ndash;84.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eCompher C, Bingham AL, McCall M, Patel J, Rice TW, Braunschweig C, et al. Guidelines for the provision of nutrition support therapy in the adult critically ill patient: The American Society for Parenteral and Enteral Nutrition. J Parenter Enter Nutr. 2022;46(1):12\\u0026ndash;41.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eArabi YM, Aldawood AS, Haddad SH, Al-Dorzi HM, Tamim HM, Jones G, et al. Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults. N Engl J Med. 2015;372(25):2398\\u0026ndash;408.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eChapman M, Peake SL, Bellomo R, Davies A, Deane A, Horowitz M, et al. Energy-Dense versus Routine Enteral Nutrition in the Critically Ill. N Engl J Med. 2018;379(19):1823\\u0026ndash;34.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHarvey SE, Parrott F, Harrison DA, Bear DE, Segaran E, Beale R, et al. Trial of the Route of Early Nutritional Support in Critically Ill Adults. N Engl J Med. 2014;371(18):1673\\u0026ndash;84.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePardo E, Lescot T, Preiser J-C, Massanet P, Pons A, Jaber S, et al. Association between early nutrition support and 28-day mortality in critically ill patients: the FRANS prospective nutrition cohort study. Crit Care. 2023;27(1):7.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eZhang D, Li H, Li Y, Qu L. Gut rest strategy and trophic feeding in the acute phase of critical illness with acute gastrointestinal injury. Nutr Res Rev. 2019;32(2):176\\u0026ndash;82.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eDoig GS, Simpson F, Sweetman EA, Finfer SR, Cooper DJ, Heighes PT, et al. Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition: a randomized controlled trial. JAMA. 2013;309(20):2130\\u0026ndash;8.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eCasaer MP, Wilmer A, Hermans G, Wouters PJ, Mesotten D, Van den Berghe G. Role of disease and macronutrient dose in the randomized controlled EPaNIC trial: a post hoc analysis. Am J Respir Crit Care Med. 2013;187(3):247\\u0026ndash;55.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSupinski GS, Schroder EA, Callahan LA. Mitochondria and Critical Illness. Chest. 2020;157(2):310\\u0026ndash;22.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003evan Zanten ARH, De Waele E, Wischmeyer PE. Nutrition therapy and critical illness: practical guidance for the ICU, post-ICU, and long-term convalescence phases. Crit Care. 2019;23(1):368.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ede Man AME, Gunst J, Reintam Blaser A. Nutrition in the intensive care unit: from the acute phase to beyond. Intensive Care Med. 2024;50(7):1035\\u0026ndash;48.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eWang Y, Li Y, Li Y, Li H, Zhang D. Enteral feeding strategies in patients with acute gastrointestinal injury: From limited to progressive to open feeding. Nutrition. 2023;117:112255.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSchetz M, De Jong A, Deane AM, Druml W, Hemelaar P, Pelosi P, et al. Obesity in the critically ill: a narrative review. Intensive Care Med. 2019;45(6):757\\u0026ndash;69.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eShapiro ML, Komisarow J. The Obesity Paradox and Effects of Early Nutrition: Is There a Paradox, or Is There Not? Crit Care Med. 2017;45(5):918\\u0026ndash;9.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eDickerson RN, Andromalos L, Brown JC, Correia M, Pritts W, Ridley EJ, et al. Obesity and critical care nutrition: current practice gaps and directions for future research. Crit Care. 2022;26(1):283.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSinger P, Blaser AR, Berger MM, Alhazzani W, Calder PC, Casaer MP, et al. ESPEN guideline on clinical nutrition in the intensive care unit. Clin Nutr. 2019;38(1):48\\u0026ndash;79.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMoonen HPFX, Beckers KJH, van Zanten ARH. Energy expenditure and indirect calorimetry in critical illness and convalescence: current evidence and practical considerations. J Intensive Care. 2021;9(1):8.\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Critically ill patients, Acute gastrointestinal injury, Body mass index, Feeding strategies, Nutrition\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-6005098/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-6005098/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003eObjective\\u003c/h2\\u003e \\u003cp\\u003eNutritional support is crucial for critically ill patients. Body mass index (BMI) represents nutritional reserves to some extent, but it is unclear whether the U-shaped relationship between caloric delivery during the acute phase of critical illness and prognosis applies to patients across all BMI categories.\\u003c/p\\u003e\\u003ch2\\u003eMethods\\u003c/h2\\u003e \\u003cp\\u003eThis secondary analysis of a multicenter prospective observational study, which included patients who were admitted to the intensive care unit (ICU) for at least 3 days. The patients were divided into two subgroups based on BMI: normal BMI and overweight (BMI\\u0026thinsp;\\u0026gt;\\u0026thinsp;25 kg/m\\u0026sup2;). We used univariate and multivariate Cox regression analyses to investigate the relationship between calorie delivery within the first 72 hours of ICU admission and 28-day mortality, and to explore whether a non-linear relationship exists between the two.\\u003c/p\\u003e\\u003ch2\\u003eResults\\u003c/h2\\u003e \\u003cp\\u003eA total of 361 patients were included in the final analysis, including 272 in the normal BMI subgroup and 89 in the overweight subgroup. In the normal BMI subgroup Cox regression, there was a significant non-linear relationship (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.003) and association (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.002) between daily delivered calories and 28-day mortality. Increasing the daily delivered calories from 0 to 18 kcal/kg/day was associated with decreasing mortality (hazard ratio (HR) 0.892, 95% CI 0.816\\u0026ndash;0.975), while the daily delivered calories\\u0026thinsp;\\u0026gt;\\u0026thinsp;18 kcal/kg/day was associated with increasing mortality (HR 1.116, 95% CI 1.016\\u0026ndash;1.227)); In the overweight subgroup, higher daily delivered calories was also observed to increase mortality (HR 1.124, 95% CI 1.043\\u0026ndash;1.211, \\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.003), but this non-linear relationship disappeared (P\\u0026thinsp;=\\u0026thinsp;0.466). After adjustment, the above results still hold up.\\u003c/p\\u003e\\u003ch2\\u003eConclusions\\u003c/h2\\u003e \\u003cp\\u003eThe U-shaped relationship between daily delivered calories within the first 72 hours of ICU admission and 28-day mortality in critically ill patients applies only to those with BMI\\u0026thinsp;\\u0026lt;\\u0026thinsp;25 kg/m\\u0026sup2;, and no such U-shaped curve was observed in patients with BMI\\u0026thinsp;\\u0026gt;\\u0026thinsp;25 kg/m\\u0026sup2;. Further research is still needed to validate this conclusion.\\u003c/p\\u003e\",\"manuscriptTitle\":\"The U-shaped Curve of Energy Supply in the First 72 Hours of Critical Illness May Apply Only to Patients with Normal Body Mass Index: A Post-hoc Analysis of a Prospective Observational Multicenter Study\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-02-14 13:29:36\",\"doi\":\"10.21203/rs.3.rs-6005098/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"4170f2c6-63cc-4214-8353-5c3fe0dba325\",\"owner\":[],\"postedDate\":\"February 14th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2025-04-28T14:08:28+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2025-02-14 13:29:36\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-6005098\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-6005098\",\"identity\":\"rs-6005098\",\"version\":[\"v1\"]},\"buildId\":\"8U1c8b4HqxoKbykW_rLl7\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}