Early urea-to-creatinine ratio to predict rapid muscle loss in critically ill patients with sepsis: a retrospective observational study

Early urea-to-creatinine ratio to predict rapid muscle loss in critically ill patients with sepsis: a retrospective observational 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 Early urea-to-creatinine ratio to predict rapid muscle loss in critically ill patients with sepsis: a retrospective observational study Jie Jiang, Hui Chen, Shan-shan Meng, Chun Pan, Jian-Feng Xie, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5239381/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Jan, 2025 Read the published version in BMC Anesthesiology → Version 1 posted 4 You are reading this latest preprint version Abstract Background Sepsis patients in the ICU often experience rapid muscle loss. Urea-to-creatinine ratio (UCR) reflects protein metabolism and is often used to assess nutritional metabolic status. This study aimed to investigate whether the UCR can predict the development of rapid muscle loss in patients with sepsis. Methods Our retrospective observational study was performed in a university ICU from 2014 to 2021 on adult (≥ 18 years) sepsis patients. The primary outcome was the incidence of rapid muscle loss during ICU hospitalization. We utilized multivariate logistical regression to characterize the association between UCR/ΔUCR and rapid muscle loss. The area under curve (AUC) of the receiver operating characteristic (ROC) curve was calculated to quantify the performance of UCR/ΔUCR in predicting rapid muscle loss. Results Among all 482 patients, 141 patients (29.2%) had rapid muscle loss during ICU stay. Multivariate logistic regression analysis showed that ΔUCR was associated with an increased risk of rapid muscle loss, the Odds ratio was 1.02 [95% CI: 1.01,1.02]. The predictive ability of ΔUCR for rapid muscle loss was 0.76[95% CI 0.68–0.83]. The threshold was 19.4 for ΔUCR. Conclusion Our findings show that elevated UCR is independently associated with rapid muscle loss, and it can predict rapid muscle loss in sepsis patients. UCR provides a simple bedside marker for early identification and intervention of rapid muscle loss. Sepsis skeletal muscle wasting Urea-to-creatinine ratio ICU acquired weakness Figures Figure 1 Figure 2 Figure 3 1. INTRODUCTION During the first week of hospitalization in the ICU, there may be significant muscle loss of over 10%, which often leads to functional damage and weakness among ICU survivors [ 1 – 2 ] . Skeletal muscle mass is crucial in immune function, glucose processing, protein synthesis, and mobility; therefore, acute loss of skeletal muscle mass can lead to excessive physiological damage [ 3 – 5 ] , and even lead to weakness in the intensive care unit (ICU). ICU acquired weakness (ICUAW) is a serious and recurrent complication originating from critical illness, with an incidence rate ranging from 25–75% [ 6 ] . Compared with other no sepsis patients, the incidence of this disease in sepsis patients has significantly increased [ 7 – 9 ] . The acute loss of skeletal muscle mass leads to long-term dependence on mechanical ventilation and prolonged hospitalization, thereby increasing medical expenses and mortality. In addition, it is associated with sustained impairment of health-related quality of life, which may persist for several years after discharge from the ICU [ 10 – 14 ] . Skeletal muscle mass can be estimated by various techniques and adjusted based on height or BMI [ 15 ] . Magnetic resonance imaging (MRI) and computed tomography (CT) are considered the gold standards for non-invasive assessment of muscle mass. In particular, the CT images of specific lumbar spine markers (L3) are significantly correlated with systemic muscles, which has been proven to be practical and accurate for measuring body composition [ 16 – 18 ] . Therefore, this imaging method has been used to detect muscle mass. However, the high cost, radiation exposure caused by CT, and inconvenience in screening limit the application of CT and MRI. The ratio of urea to creatinine (UCR) reflects protein metabolism, and its sustained increase reflects muscle catabolism, muscle bioenergy depletion, and ongoing muscle atrophy [ 19 ] . Thus, it helps in assessing nutritional metabolic status. Recently, Haines reported [ 20 ] that elevated UCR can be used as a potential biomarker of muscle catabolism after severe trauma and persistent critical illness. Early acute muscle mass loss in sepsis patients is the result of increased catabolism and decreased anabolism, which may lead to increased UCR. However, previous studies have not explored the relationship between UCR levels and acute skeletal muscle wasting. The purpose of this study was to investigate whether early elevated UCR could predict acute skeletal muscle wasting in septic patients. 2. METHODS 2.1 Study population This is a single-center retrospective observational study on septic patients admitted to the ICU of a university hospital from January 2014 to December 2021. Sepsis was diagnosed according to the sepsis-3 criteria [ 21 ] ; in brief, patients with documented or suspected infection and an acute change in total Sequential Organ Failure Assessment (SOFA) score of ≥ 2 points were considered to have sepsis. Patients were eligible if they were 18 years of age or older, and at least 5 days of ICU stay, and availability of at least two serial CT datasets including the abdomen during hospitalization. We excluded patients if (1) they had creatinine > 354umol/l on ICU admission, (2) received renal replacement therapy (RRT), (3) failed to match to complete data records, (4) transferred from another ICU, and (5) the interval between two serial CT datasets shorter than 5 days. The study was approved by the ethics committees of Zhongda Hospital, Southeast University (Number 2021ZDSYLL225-P01) and performed in accordance with STROBE [ 22 ] guideline for observational research. 2.2 Data collection For all patients, the following demographic and clinical data were collected from electronic health records: sex, age, height and weight, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE) II score, chronic comorbidities, admission diagnosis, and infection site. We recorded the creatine kinase, myoglobin, hemoglobin, albumin (ALB), prognostic nutritional indicators (PNI), blood glucose, lymphocyte count, procalcitonin (PCT), and lactate on day 1 after ICU admission. Urea nitrogen, and creatinine were extracted on day 1 and day 3. In addition, we collected the mode of nutritional support, daily caloric capacity, neuromuscular blockers use, Richmond agitation-sedation scale (RASS) score, and insulin dose. PNI was calculated as 10 × serum ALB level (g/L) + 0.005 × total lymphocyte count (/mm3). 2.3 L3 skeletal muscle area analysis CT images of the third lumbar vertebra (L3) were evaluated. For all patients included, skeletal muscle area at L3 slices (L3SMA) includes the psoas, erector spine, quadratus lumborum, transverse abdominous, external and internal obliques, and rectus abdominous. Images were analyzed by a trained specialist (J.J) with Image J software [ 23 ] version 1.48 ( https://imagej.nih.gov/ij/index.html ; NIH, Bethesda, MD, USA), which used predetermined thresholds (-29 to + 150 Hounsfield units) to demarcate skeletal muscle tissues [ 6 ] . Tissue boundaries were manually corrected if needed. L3SMA was calculated automatically by summing the skeletal muscle-tissue pixels and multiplying them by the surface area of each pixel. Figure 1 shows the before and after changes in L3SMA (red) on transverse CT images in the same patient. L3SMA was adjusted by the square of the height (SMA/height2), which was referred to as the skeletal muscle index (L3SMI). L3SMI = L3SMA/ height 2. L3SMA was assessed on ICU admission and at least one more in-ICU follow-up CT. If the patient had more than twice upper abdominal CT scans during the ICU stay, only the first and second CT scan results were evaluated. According to previous research, in the first week of critical illness, patients lose approximately 2% of their muscle mass per day, so we define rapid muscle loss as △L3SMA > 2% per day obtained from admission CT L3 muscle area and follow-up CT L3 muscle area [ 24 ] , as follows: $$\:△\:\text{L}3\text{S}\text{M}\text{A}=\frac{\text{a}\text{d}\text{m}\text{i}\text{s}\text{s}\text{i}\text{o}\text{n}\:\text{C}\text{T}\:\text{L}3\text{S}\text{M}\text{A}\:-\:\:\text{F}\text{o}\text{l}\text{l}\text{o}\text{w}\:\text{u}\text{p}\:\text{C}\text{T}\:\text{L}3\text{S}\text{M}\text{A}\:}{\text{a}\text{d}\text{m}\text{i}\text{s}\text{s}\text{i}\text{o}\text{n}\:\text{C}\text{T}\:\text{L}3\text{S}\text{M}\text{A}}$$ 2.4 Primary exposures and Outcomes The primary exposures were UCR on day 1 (UCR_D1), which was calculated as [urea nitrogen*1000/ creatinine], UCR on day 3 (UCR_D3), and the difference in UCR between day 3 and day 1 (ΔUCR). The primary outcome was the incidence of rapid muscle loss during ICU hospitalization. The secondary outcomes included ICU and hospital length of stay, ICU mortality, 28-day mortality, hospital mortality, and ventilation-free days (VFDs) on day 28. 2.5 Statistical analysis Values are presented as the mean (standard deviation) or median [interquartile range (IQR)] for continuous variables as appropriate and as the total number (percentage) for categorical variables. Comparisons between rapid muscle loss and no rapid muscle loss patients were made using the X2 test or Fisher’s exact test for categorical variables and Student’s t-test or Mann-Whitney U test for continuous variables as appropriate. We first employed three multivariate logistic regression models to explore the association between UCR/ΔUCR and rapid muscle loss. Variables based on previous studies and clinical correlations including age, gender, BMI, SOFA score, Lactate, PCT, L3SMA, and PNI were entered into the model. We calculated the area under curve (AUC) of the receiver operating characteristic (ROC) curve to quantify the performance of UCR/ΔUCR in predicting rapid muscle loss. The optimal cut-off value of UCR/ΔUCR was determined by the Youden Index (sensitivity + specificity − 1). We also calculated the AUROCs after adjusting for the above confounders. The AUCs were compared by using the bootstrap test for each two ROC curves. Several subgroup analyses were performed according to sex, age (≥ 60, < 60), Diabetes mellitus, BMI (≥ 24, < 24), SOFA score (≥ 8, < 8), PNI (≥ 34, < 34), L3SMI (≥ 40, < 40), use of mechanical ventilation, insulin, nutrition supports, neuromuscular blocker and vasopressor. We used Stata software version 15.0 (Stata Corp) and R software (IBM, Armonk, NY version 4.0.3) for all analyses. 2-tailed P < 0 .05 was considered to be statistically significant. 3. RESULT 3.1 Baseline characteristics and clinical outcomes A total of 482 patients were included in the final analysis. The flow diagram of study patients was presented in Fig. 2 . The median (IQR) age of the included patients was 62.0 (51.0, 74.0) years, with 350 males and 132 females (Table 1 ). Patients had a median SOFA score of 8 (6, 11) and a median APACHE II score of 19(14, 24). Among them, 141 patients (29.2%) had Rapid muscle loss during ICU stay. There was no significant difference in L3SMA between the two groups upon admission, and subsequently, L3SMA in both groups tended to decrease. However, the rapid muscle loss group showed a greater decrease in L3SMA, Δ L3SMA is (20.65 [0.55], 14.54 [0.47], P < 0.01) (Figure S1 and Table S1 ). In CT re-examination within one week group, the decline rate was faster than in CT re-examination out of one week group (1.89 [0.87], 1.56 [0.56], P < 0.01) (Table S2). Tables 1 and S3 summarize the clinical characteristics of the rapid muscle loss group and the group without rapid muscle loss. Compared with the group without rapid muscle loss, patients with rapid muscle loss had a lower average age (56.00 [50.00, 71.00], 64.00 [51.00, 75.00], P = 0.02), the proportion of male patients is higher (118 [83.69%], 232 [68%], P < 0.01), UCR-D3 and Δ UCR significantly increased. There was no significant difference between the two groups in terms of 28-day mortality, ICU mortality, and length of hospitalization. Table 1 Baseline characteristics and clinical outcomes of patients. BMI, body mass index; APACHE II, acute physiology and chronic health evaluation II; SOFA, sequential organ failure assessment; UCR, urea-to-creatinine ratio; PCT, procalcitonin; RR, Respiratory rate; MAP, mean arterial pressure; L3SMA, skeletal muscle area at L3 slices; VFDs-28-day, mechanical ventilation free days to day28. * p < 0 .05. Characteristics All patients (N = 482) Rapid muscle loss group(N = 141) Non rapid muscle loss group (N = 341) p Age (year) (median [IQR]) 62.00 (51.00, 74.00) 56.00 (50.00, 71.00) 64.00 (51.00, 75.00) 0.02* Male (n) (%) 350 (72.61) 118 (83.69) 232 (68) < 0.01* Infection site Respiratory (n) (%) 295 (61.20) 81 (57.41) 214 (62.76) 0.28 Abdominal (n) (%) 127 (26.35) 44 (31.21) 83 (24.34) 0.12 Genitourinary (n) (%) 13 (2.70) 4 (2.84) 9 (2.64) 0.9 Skin/soft tissue (n) (%) 7 (1.45) 1 (0.71) 6 (1.76) 0.38 Bloodstream (n) (%) 22 (4.56) 6 (4.26) 16 (4.69) 0.83 Central nervous system (n) (%) 15 (3.11) 4 (2.84) 11 (3.22) 0.82 Other (n) (%) 3 (0.62) 1 (0.71) 2 (0.59) 0.88 BMI (median [IQR]) 23.74 (21.72, 26.06) 24.46 (22.86, 27.34) 23.44 (20.96, 25.25) 0.21 APACHE II (median [IQR]) 19.00 (14.00, 24.00) 18.00 (13.00, 23.00) 19.00 (14.00, 24.00) 0.63 SOFA (median [IQR]) 8.00 (6.00, 11.00) 8.00(6.00, 11.00) 8.00 (6.00, 11.00) 0.59 Shock (n) (%) 276 (57.38) 157 (57.93) 119 (56.39) 0.74 Comorbid conditions Hypertension (n) (%) 213 (44.19) 52 (36.88) 161 (47.21) 0.04* Coronary artery disease (n) (%) 62 (12.86) 14 (9.93) 48 (14.07) 0.22 Heart failure (n) (%) 60 (12.45) 15 (10.64) 45 (13.19) 0.44 Chronic obstructive pulmonary disease (n) (%) 27 (5.60) 8 (5.67) 19 (5.57) 0.96 Diabetes mellitus (n) (%) 119 (24.69) 33 (23.4) 86 (25.21) 0.67 Solid malignant tumors (n) (%) 71 (14.73) 14 (9.93) 57 (16.72) 0.05 Hematologic cancer (n) (%) 6 (1.25) 1 (0.71) 5 (1.47) 0.49 Cirrhosis (n) (%) 7 (1.45) 2 (1.42) 5 (1.47) 0.97 Other (n) (%) 11 (2.28) 3 (2.13) 8 (2.35) 0.91 Admission vital signs Temperature (°C) (median [IQR]) 37.2 (36.5, 38.5) 37.4 (36.5, 38.3) 37.2 (36.5, 38.5) 0.69 RR (median [IQR]) 21(12, 28) 20(12, 28) 21(13, 28) 0.66 Heart rate (beats/min) (median [IQR]) 111(73, 126) 111(80, 125) 111(72, 127) 0.90 MAP (mmHg) (median [IQR]) 75.00 (71.00, 78.00) 76.00 (72.00, 78.00) 75.00 (70.00, 78.50) 0.54 Admission blood tests (median [IQR]) Creatinine (umol/L) (median [IQR]) 78.00 (59, 107) 82.00 (63, 109) 77.00 (56, 103) 0.73 Urea (umol/L) (median [IQR]) 6900(4700, 10400) 6800 (5100, 9200) 6900(4600, 10700) 0.17 Urea: creatinine (median [IQR]) 88.55 (61.42, 123.08) 84.21 (62.50, 110.53) 92.50 (61.43, 132.71) 0.02* Lactate (mmol/L) (median [IQR]) 1.60 (1.10, 2.50) 1.50 (1.10, 2.30) 1.60 (1.10, 2.60) 0.86 PCT (ng/ml) (median [IQR]) 0.89 (0.14, 4.82) 1.02 (0.2, 3.18) 0.88 (0.13, 5.68) 0.23 Albumin (g/L) (median [IQR]) 30.20 (27.00, 34.00) 29.90 (27.00, 33.80) 30.20 (26.90, 34.00) 0.68 Lymphocyte count (×10 9 /L) (median [IQR]) 0.70 (0.47, 1.09) 0.74 (0.52, 1.15) 0.69 (0.46, 1.07) 0.21 Hemoglobin (g/L) (median [IQR]) 106.00 (91.00, 123.00) 105.00 (89.00, 125.00) 106.00 (92.00, 122.00) 0.93 Admission L3SMA (cm 2 ) mean (SD) 118.96 (32.28) 141.66 (30.11) 109.58 (28.26) < 0.01* Hospital length of stay (day) (mean [SD]) 31.40 (20.59) 28.82 (17.13) 32.47 (21.8) 0.08* ICU length of stay (day) (median [IQR]) 16 (11, 26) 15 (10, 24) 17 (11,26) 0.13 Hospital mortality (n) (%) 105 (21.78) 24 (17.02) 81 (23.75) 0.10 ICU mortality (n) (%) 92 (19.09) 20 (14.19) 72 (21.11) 0.08 28-day mortality (day) (%) 76 (15.77) 21 (14.89) 55 (16.13) 0.74 Alive and VFDs-28-day (day) (median [IQR]) 20.35 (7.56141) 20.46 (7.27) 20.3 (7.68) 0.85 In addition, a separate analysis of 176 patients who underwent CT re-examination within one week revealed that 67 patients (38.1%) had rapid muscle loss. There was no significant difference in 28-day mortality or ICU mortality between patients with and without rapid muscle loss, but the length of hospitalization was longer than in patients without rapid muscle loss (28.5 [2.1], 21.9 [1.16], P < 0.01) (Table S4). BMI, body mass index; APACHE II, acute physiology and chronic health evaluation II; SOFA, sequential organ failure assessment; UCR, urea-to-creatinine ratio; PCT, procalcitonin; RR, Respiratory rate; MAP, mean arterial pressure; L3SMA, skeletal muscle area at L3 slices; VFDs-28-day, mechanical ventilation free days to day28. * p < 0 .05. 3.2 Association between UCR and rapid muscle loss The multivariate logistic regression analysis showed that UCR_D1 and UCR_D3 were not associated with an increased risk of rapid muscle loss, while there was a significant association between ΔUCR and rapid muscle loss, with an OR of 1.02 [95% CI: 1.01,1.02] (Table 2 ). The comparisons were similiar after adjusing for confounders. Table 2 Multivariate logistic regression exploring the impact of UCR on the risk of rapid muscle loss. Adjusted for UCR_D1 Adjusted for UCR_D3 Adjusted for ΔUCR OR (95% CI) P value OR (95% CI) P value OR (95% CI) P value Age 0.99 (0.97,1.00) 0.03* 0.99 (0.99,1.00) 0.02* 0.99 (0.99,0.99) 0.02* Male 0.95 (0.58,1.56) 0.85 0.99 (0.61,1.63) 0.98 0.95 (0.58,1.56) 0.99 BMI 0.96 (0.89,1.03) 0.25 0.96 (0.90,1.03) 0.29 0.96 (0.89,1.03) 0.31 SOFA 0.99 (0.94,1.06) 0.86 0.99 (0.93,1.05) 0.79 0.99 (0.94,1.06) 0.65 L3SMA on Day 1 1.00 (0.99,1.01) 0.76 1.00 (0.99,1.01) 0.86 1.00 (0.98,1.01) 0.89 Lactate 1.00 (0.92,1.09) 0.96 1.02 (0.93,1.11) 0.69 1.00 (0.91,1.09) 0.69 PCT 0.98 (0.95,1.01) 0.16 0.98 (0.95,1.01) 0.22 0.98 (0.95,1.01) 0.13 PNI 0.99 (0.97,1.02) 0.68 0.99 (0.97,1.02) 0.68 0.99 (0.68,1.02) 0.75 UCR_D1 1.00 (0.99,1.01) 0.07 — — — — UCR_D3 — — 1.00 (0.99,1.00) 0.61 — — ΔUCR — — — — 1.02 (1.01,1.02) < 0.01* The reference group was non rapid muscle loss. OR, odds ratio; CI, Confidence interval; SOFA, sequential organ failure assessment; BMI, body mass index; PCT, procalcitonin; PNI, prognostic nutritional index; L3SMA, skeletal muscle area at L3 slices; UCR, urea-to-creatinine ratio; UCR_D1, urea-to-creatinine ratio on day1; UCR_D3, urea-to-creatinine ratio on day3; ΔUCR, difference in UCR between day 3 and day 1. *: p < 0 .01. In patients who underwent CT re-examination within one week, ΔUCR is still associated with rapid muscle loss (Table S5). Analysis of the predictive values of UCR_D1, UCR_D3 and ΔUCR for rapid muscle loss showed that UCR_D1 and UCR_D3 had poor predictive accuracy (AUROC 0.46 and 0.57). ΔUCR had the highest predictive accuracy (AUROC 0.76) (Figure. 3). ΔUCR had an optimal threshold of 19.4 for the prediction of rapid muscle loss, with sensitivity and specificity of 60% (49–83) % and 84% (61–95) %, respectively. The positive predictive value was 70% (67–93) % and the negative predictive value was 77% (68–85) %. The Youden index was 0.44 (Table 3 ). Table 3 The accuracy of UCR to predict rapid muscle loss in CT re-examination within one week group. AUROC, area under the receiver operating characteristic; UCR, urea-to-creatinine ratio; UCR_D1, urea-to-creatinine ratio on day1; UCR_D3, urea-to-creatinine ratio on day3; ΔUCR, difference in UCR between day 3 and day 1. AUROC Threshold Sensitivity, % Specifcity, % Positive predictive value, % Negative predictive value, % UCR_D1 0.46 (0.37–0.54) > 48 0.88 (0.76–0.97) 0.17 (0.12–0.37) 0.39 (0.31–0.69) 0.68 (0.52–0.75) UCR_D3 0.57 (0.49–0.66) > 70.7 0.84 (0.49–0.91) 0.37 (0.29–0.73) 0.45(0.36–0.54) 0.78 (0.69–0.83) ΔUCR 0.76 (0.68–0.83) > 19.4 0.60 (0.49–0.83) 0.84 (0.61–0.95) 0.70 (0.67–0.93) 0.77 (0.68–0.85) AUROC, area under the receiver operating characteristic; UCR, urea-to-creatinine ratio; UCR_D1, urea-to-creatinine ratio on day1; UCR_D3, urea-to-creatinine ratio on day3; ΔUCR, difference in UCR between day 3 and day 1. 3.3 Subgroup analyses Regardless of the subgroup, ΔUCR was associated with a higher probability of rapid muscle loss. No significant differences were observed among the subgroups. However, subgroup analysis in patients who underwent CT re-examination within one week showed that in the age subgroup, the AUROC of rapid muscle loss predicted by Δ UCR was significantly higher in patients aged ≥ 60 years than in patients aged < 60 years (0.82 [95% CI 0.74–0.91] vs. 0.67 [95% CI 0.55–0.79], P = 0.04). In the nutritional support subgroup, the AUROC of rapid muscle loss predicted by Δ UCR was significantly higher in patients without nutritional support than in patients with nutritional support (0.79 [95% CI 0.72–0.87 vs 0.58 [95% CI 0.39–0.78], P = 0.04) (Table S6 and Figure S2). 4. DISCUSSION In this study, we found that 29.2% of patients experienced rapid muscle loss during their ICU stay. The rate of decline was faster in the early stages of ICU (within a week) than in the later stages. Patients who showed rapid muscle loss within one week of ICU admission had longer hospitalization. UCR was confirmed to be independently associated with rapid muscle loss by analyzing patients' abdominal CT scans and biochemical markers. An early elevated UCR helped predict the development of rapid muscle loss. in patients with sepsis. The pronounced muscle wasting that contributed to the weakness of myogenic origin in sepsis patients was explained by the catabolic state of critical illness, with decreased anabolic effector hormones and increased catabolic hormones [ 25 , 26 ] , as well as the mechanical unloading brought on by immobilization or denervation. This metabolic disorder led to an increase in protein catabolism and a decrease in anabolism [ 1 ] . Increased protein catabolism led to increased urea production, and increased catabolism brought about a decrease in total muscle mass and a decrease in creatinine levels; which eventually increased UCR. Therefore, an early increase in the UCR would help predict the occurrence of rapid muscle loss in sepsis patients. Haines reported [ 20 ] that in patients after major trauma with ICU stay ≥ 10 days, UCR on day 10 had increased by 133%. Elevated UCR was a biochemical marker indicating persistent critical illness after major trauma and was seen in association with the wasting of skeletal muscle. In other investigations on nutrient metabolism, the UCR had also been found to be a usable clinical biomarker of muscle catabolism conditions in critical diseases [ 27 – 29 ] . We conducted a separate analysis on patients who underwent CT re-examination within one week of staying in the ICU. The results showed that early increase in the UCR had a higher accuracy in predicting rapid muscle loss in CT re-examination within one week group. This result can be explained in subgroup analysis. Subgroup analysis showed that the implementation of enteral nutrition would reduce the value of UCR in predicting rapid muscle loss. With the extension of ICU stay time, including the implementation of nutritional support and protein intake, the body has shifted from early catabolism to a complex state of coexistence of catabolism and synthetic metabolism, masking the early protein metabolism disorder in sepsis patients. Therefore, the predictive value of UCR as a marker reflecting protein breakdown metabolism will decrease. Critically ill patients may develop rapid muscle loss as early as the day after admission to ICU [ 30 ] , and the incidence increases as the length of ICU stay increases. 24%-55% of patients develop ICUAW when the length of ICU stays is extended to 5–7 days, and the incidence can further increase to 75% [ 31 ] when the length of ICU stay exceeds 10 days. The incidence of rapid muscle loss of critically ill patients with sepsis in this study is similar to that in the above studies. In terms of prognosis, we discovered that in the rapid muscle loss group patients had longer hospital stays, which is consistent with other relevant studies [ 10 ] . Previous studies [13–14,32−34] have shown that rapid muscle loss affects not only the short-term prognosis of patients but also the long-term quality of survival after discharge; yet, the present study failed to follow up on the long-term prognosis of the patients. The study has several limitations. First, the effects of rapid muscle loss on long-term survival and quality of survival were not evaluated. Second, patients who underwent RRT were excluded from this study because it was considered that the removal of urea and creatinine by RRT would interfere with the study results, which may lead to population bias. Third, this study only evaluated muscle loss and did not assess changes in patient muscle strength, so it cannot be determined whether the patient has developed ICUAW. Finally, this was a retrospective observational study, and no clear causal conclusion could be drawn. 5. CONCLUSION Approximately one-third (29.2%) of critically ill patients with sepsis will experience rapid muscle loss. Elevated UCR is independently associated with rapid muscle loss, and it can predict rapid muscle loss in sepsis patients. UCR provides a simple bedside marker for early identification and intervention of rapid muscle loss. Abbreviations CT：computed tomography; ICUAW：Intensive care unit-acquired weakness; SOFA：sequential organ failure score; RRT：renal replacement therapy; UCR：urea-to-creatinine ratio; ΔUCR d3-d1：UCR on day 3 minus UCR on day 1; ΔUCR d5-d1： UCR on day 5 minus UCR on day 1; SMI：skeletal muscle index; L3：third lumbar spine; L3SMA：skeletal muscle area at the third lumbar vertebra slices; L3SMI：skeletal muscle index at the third lumbar vertebra slices; APACHE II: Acute Physiology and Chronic Health Evaluation II; ICU: Intensive care unit; LOS: Length of stay; IQR: Interquartile range; OR: Odds ratio; PCT：procalcitonin; PNI：prognostic nutritional indicators; RASS score：Richmond Agitation-Sedation Scale score; CRP：C-reactive protein; BMI：Body Mass Index; VFDs：mechanical ventilation free days; AUROC：area under the receiver operating characteristic; CI：confidence interval. Declarations Ethics approval This study was approved by the Ethics Committees for Clinical Research of Zhongda Hospital, Southeast University (Number 2021ZDSYLL225-P01). All participants or their legal representatives have signed informed consent. The study complied with the Declaration of Helsinki and its amendments. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author Contribution F.G.: Designed the study. J.J.:Writing a manuscript. J.X., P.C. and H.C.: Assist in editing and reviewing manuscripts. S.M.: Help for data collection and analysis. All authors have contributed to the article and agree to the submitted version. Acknowledgements Not applicable. Availability of data The datasets generated and analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request. References Puthucheary ZA, et al. Acute skeletal muscle wasting in critical illness. JAMA. 2013;310(15):1591–600. Derde S, et al. Muscle atrophy and preferential loss of myosin in prolonged critically ill patients. Crit Care Med. 2012;40(1):79–89. Looijaard WGPM, Molinger J, Weijs PJM. Measuring and monitoring lean body mass in critical illness. Curr Opin Crit Care. 2018;24(4):241–7. Wieske L, et al. Neurofilaments as a plasma biomarker for ICU-acquired weakness: An observational pilot study. Crit Care. 2014;18:1–9. Gunst J, et al. Impact of early parenteral nutrition on metabolism and kidney injury. J Am Soc Nephrol. 2013;24(6):995–1005. Gomez-Perez SL, et al. Measuring Abdominal Circumference and Skeletal Muscle From a Single Cross-Sectional Computed Tomography Image: A Step-by-Step Guide for Clinicians Using National Institutes of Health ImageJ. JPEN J Parenter Enter Nutr. 2016;40(3):308–18. Schefold JC, Bierbrauer J, Weber-Carstens S. Intensive care unit-acquired weakness (ICUAW) and muscle wasting in critically ill patients with severe sepsis and septic shock. J Cachexia Sarcopenia Muscle. 2010;1(2):147–57. Thille AW, et al. Role of ICU-acquired weakness on extubation outcome among patients at high risk of reintubation. Crit Care. 2020;24(1):86. Shepherd SJ, Newman R, Brett SJ, Griffith DM. Enhancing rehabilitation after critical illness programme study investigators. Pharmacological therapy for the prevention and treatment of weakness after critical illness: A systematic review. Crit Care Med. 2016;44(6):1198–205. Vanhorebeek I, Latronico N, Van den Berghe G. ICU-acquired weakness. Intensive Care Med. 2020;46(4):637–53. Soares MN, et al. Skeletal muscle alterations in patients with acute Covid-19 and post-acute sequelae of Covid-19. J Cachexia Sarcopenia Muscle. 2022;13(1):11–22. Menges D, et al. Systematic early versus late mobilization or standard early mobilization in mechanically ventilated adult ICU patients: systematic review and meta-analysis. Crit Care. 2021;25(1):16. Kress JP. Hall JB.ICU-acquired weakness and recovery from critical illness. N Engl J Med. 2014;370(17):1626–35. Van Aerde N, et al. Five-year impact of ICU-acquired neuromuscular complications: a prospective, observational study. Intensive Care Med. 2020;46(6):1184–93. Amini B, Boyle SP, Boutin RD, Lenchik L. Approaches to Assessment of Muscle Mass and Myosteatosis on Computed Tomography: A Systematic Review. J Gerontol Biol Sci Med Sci. 2019;74:1671–8. Kim KM, Jang HC, Lim S. Differences among skeletal muscle mass indices derived from height-, weight-, and body mass index-adjusted models in assessing sarcopenia. Korean J Intern Med. 2016;31:643–50. Schweitzer L, et al. What is the best reference site for a single MRI slice to assess whole-body skeletal muscle and adipose tissue volumes in healthy adults? Am J Clin Nutr. 2015;102:58–65. Yip C, et al. Imaging body composition in cancer patients: visceral obesity, sarcopenia and sarcopenic obesity may impact on clinical outcome. Insights Imaging. 2015;6:489–97. Gunst J, et al. Impact of early parenteral nutrition on metabolism and kidney injury. J Am Soc Nephrol. 2013;24(6):995–1005. Haines RW, et al. Elevated UCR provides a biochemical signature of muscle catabolism and persistent critical illness after major trauma. Intensive Care Med. 2019;45(12):1718–31. Seymour CW, et al. Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):762–74. Von Elm E, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453–7. Gomez-Perez SL, et al. Measuring Abdominal Circumference and Skeletal Muscle From a Single Cross-Sectional Computed Tomography Image: A Step-by-Step Guide for Clinicians Using National Institutes of Health ImageJ. JPEN J Parenter Enter Nutr. 2016;40(3):308–18. Fazzini B, et al. The rate and assessment of muscle wasting during critical illness: a systematic review and meta-analysis. Crit Care. 2023;27(1):2. Vankrunkelsven W, et al. Obesity attenuates inflammation, protein catabolism, dyslipidaemia, and muscle weakness during sepsis, independent of leptin. J Cachexia Sarcopenia Muscle. 2022;13(1):418–33. Van den Berghe G. On the neuroendocrinopathy of critical illness. perspectives for feeding and novel treatments. Am J Respir Crit Care Med. 2016;194(11):1337–48. Flower L, et al. Effect of intermittent or continuous feeding and amino acid concentration on UCR in critical illness. JPEN J Parenter Enter Nutr. 2022;46(4):789–97. Page A, Flower L, Prowle J, Puthucheary Z. Novel methods to identify and measure catabolism. Curr Opin Crit Care. 2021;27(4):361–6. Haines RW, et al. Catabolism in Critical Illness: A Reanalysis of the REducing Deaths due to OXidative Stress (REDOXS) trial. Crit Care Med. 2022;50(7):1072–82. Tennilä A, et al. Early signs of critical illness polyneuropathy in ICU patients with systemic inflammatory response syndrome or sepsis. Intensive Care Med. 2000;26(9):1360–3. Paolo F, et al. The possible predictive value of muscle ultrasound in the diagnosis of ICUAW in long-term critically ill patients. J Crit Care. 2022;71:154104. De Jonghe B, et al. Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA. 2002;288(22):2859–67. Viertel M, Bock C, Reich M, Löser S, Plauth M. Performance of CT-based low skeletal muscle index, low mean muscle attenuation, and bioelectric impedance derived low phase angle in the detection of an increased risk of nutrition related mortality. Clin Nutr. 2019;38(5):2375–80. Toledo DO, et al. The use of computed tomography images as a prognostic marker in critically ill cancer patients. Clin Nutr ESPEN. 2018;25:114–20. Additional Declarations No competing interests reported. Supplementary Files Additionalfile1.docx Cite Share Download PDF Status: Published Journal Publication published 11 Jan, 2025 Read the published version in BMC Anesthesiology → Version 1 posted Editorial decision: Revision requested 14 Oct, 2024 Editor assigned by journal 12 Oct, 2024 Submission checks completed at journal 12 Oct, 2024 First submitted to journal 10 Oct, 2024 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. 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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-5239381","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":365941719,"identity":"81406b2d-7f12-4f3a-8394-0dd38269ae21","order_by":0,"name":"Jie Jiang","email":"","orcid":"","institution":"Zhongda Hospital, Southeast University","correspondingAuthor":false,"prefix":"","firstName":"Jie","middleName":"","lastName":"Jiang","suffix":""},{"id":365941720,"identity":"e041125b-cc1a-4849-99ad-33c9be56ead3","order_by":1,"name":"Hui Chen","email":"","orcid":"","institution":"Zhongda Hospital, Southeast University","correspondingAuthor":false,"prefix":"","firstName":"Hui","middleName":"","lastName":"Chen","suffix":""},{"id":365941721,"identity":"f71c2a6a-da98-477e-a4ac-1e7f428c659e","order_by":2,"name":"Shan-shan Meng","email":"","orcid":"","institution":"Zhongda Hospital, Southeast University","correspondingAuthor":false,"prefix":"","firstName":"Shan-shan","middleName":"","lastName":"Meng","suffix":""},{"id":365941722,"identity":"457c8578-1b26-4ff4-8aac-a44d2188b6d6","order_by":3,"name":"Chun Pan","email":"","orcid":"","institution":"Zhongda Hospital, Southeast University","correspondingAuthor":false,"prefix":"","firstName":"Chun","middleName":"","lastName":"Pan","suffix":""},{"id":365941723,"identity":"cc3da633-d943-432a-aeff-908badf092c2","order_by":4,"name":"Jian-Feng Xie","email":"","orcid":"","institution":"Zhongda Hospital, Southeast University","correspondingAuthor":false,"prefix":"","firstName":"Jian-Feng","middleName":"","lastName":"Xie","suffix":""},{"id":365941724,"identity":"edada4da-7095-4a2e-ab8c-6d5d84e2ec06","order_by":5,"name":"Feng-Mei Guo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIiWNgGAWjYBAC9gYQWSEhx9je2PjwAzFaeA6AyDM2xsw9h5uNJYjWwtiWltg+I71NgIcoLWLHr0l8YDvM2DvzYRuDBIOdnG4DIS3SOWWSM3gOM0vOTmx7UMCQbGx2gIAWe+mcNGkeicNshrMT2w0kGA4kbiOkhQesxeAwj/3Ng20SPMRpST8mzZOQJsE4g5FoLTnMljMO2Bgw9iQCA9mACL8AbXl44+M/ifrG9uMPH36osJMjqAWoyQCJY4BTGTJgf0CUslEwCkbBKBjBAAD6AUHm2WC43wAAAABJRU5ErkJggg==","orcid":"","institution":"Zhongda Hospital, Southeast University","correspondingAuthor":true,"prefix":"","firstName":"Feng-Mei","middleName":"","lastName":"Guo","suffix":""}],"badges":[],"createdAt":"2024-10-10 11:53:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5239381/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5239381/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12871-025-02892-8","type":"published","date":"2025-01-11T15:57:57+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":71480695,"identity":"002905a0-42e1-44ea-bfe2-14d693f67471","added_by":"auto","created_at":"2024-12-16 05:58:35","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1140406,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTypical transverse CT images at L3 of the same patient.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ea, ICU admission；b, the tenth day after ICU admission. The total skeletal muscle area (red).\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5239381/v1/15400b303a169c92ad62a71b.png"},{"id":71480694,"identity":"eb1ebd7c-20de-4824-97b3-779425a68138","added_by":"auto","created_at":"2024-12-16 05:58:34","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":87959,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlowchart of the patients included in the study.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRRT, renal purification therapy; CT,computerized tomography; ICU, intensive care unit.\u003c/p\u003e","description":"","filename":"figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5239381/v1/3443d86a78e88c834e17704c.png"},{"id":71479531,"identity":"bb6c7f97-437a-4d31-b33c-40a80270bb4e","added_by":"auto","created_at":"2024-12-16 05:42:34","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":37539,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAUROC of predicting rapid muscle loss in sepsis patients.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA, AUROC curves for UCR/ΔUCR after adjusing for confounders.B, AUROC curves for UCR, ΔUCR.AUROC, area under the receiver operating characteristic; CI, confidence interval; UCR, urea-to-creatinine ratio; ΔUCR, difference in UCR between day 3 and day 1.\u003c/p\u003e","description":"","filename":"figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5239381/v1/e01bfdd46c1d6659a87032ec.png"},{"id":73694059,"identity":"2aba8727-66cb-4d87-86e2-840a2dda10d3","added_by":"auto","created_at":"2025-01-13 16:10:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2497415,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5239381/v1/77f31b6e-cdfd-43d9-8a7f-d70566db2f46.pdf"},{"id":71479534,"identity":"9bccc03c-32ba-4c2e-ac98-8f6bea10f17a","added_by":"auto","created_at":"2024-12-16 05:42:34","extension":"docx","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":465347,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5239381/v1/ab7e039dd4c1157679e0dba6.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Early urea-to-creatinine ratio to predict rapid muscle loss in critically ill patients with sepsis: a retrospective observational study","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eDuring the first week of hospitalization in the ICU, there may be significant muscle loss of over 10%, which often leads to functional damage and weakness among ICU survivors \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Skeletal muscle mass is crucial in immune function, glucose processing, protein synthesis, and mobility; therefore, acute loss of skeletal muscle mass can lead to excessive physiological damage \u003csup\u003e[\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e, and even lead to weakness in the intensive care unit (ICU). ICU acquired weakness (ICUAW) is a serious and recurrent complication originating from critical illness, with an incidence rate ranging from 25\u0026ndash;75% \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Compared with other no sepsis patients, the incidence of this disease in sepsis patients has significantly increased \u003csup\u003e[\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. The acute loss of skeletal muscle mass leads to long-term dependence on mechanical ventilation and prolonged hospitalization, thereby increasing medical expenses and mortality. In addition, it is associated with sustained impairment of health-related quality of life, which may persist for several years after discharge from the ICU \u003csup\u003e[\u003cspan additionalcitationids=\"CR11 CR12 CR13\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSkeletal muscle mass can be estimated by various techniques and adjusted based on height or BMI \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. Magnetic resonance imaging (MRI) and computed tomography (CT) are considered the gold standards for non-invasive assessment of muscle mass. In particular, the CT images of specific lumbar spine markers (L3) are significantly correlated with systemic muscles, which has been proven to be practical and accurate for measuring body composition \u003csup\u003e[\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. Therefore, this imaging method has been used to detect muscle mass. However, the high cost, radiation exposure caused by CT, and inconvenience in screening limit the application of CT and MRI.\u003c/p\u003e \u003cp\u003eThe ratio of urea to creatinine (UCR) reflects protein metabolism, and its sustained increase reflects muscle catabolism, muscle bioenergy depletion, and ongoing muscle atrophy \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. Thus, it helps in assessing nutritional metabolic status. Recently, Haines reported \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e that elevated UCR can be used as a potential biomarker of muscle catabolism after severe trauma and persistent critical illness. Early acute muscle mass loss in sepsis patients is the result of increased catabolism and decreased anabolism, which may lead to increased UCR.\u003c/p\u003e \u003cp\u003eHowever, previous studies have not explored the relationship between UCR levels and acute skeletal muscle wasting. The purpose of this study was to investigate whether early elevated UCR could predict acute skeletal muscle wasting in septic patients.\u003c/p\u003e"},{"header":"2. METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study population\u003c/h2\u003e \u003cp\u003eThis is a single-center retrospective observational study on septic patients admitted to the ICU of a university hospital from January 2014 to December 2021. Sepsis was diagnosed according to the sepsis-3 criteria \u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e; in brief, patients with documented or suspected infection and an acute change in total Sequential Organ Failure Assessment (SOFA) score of \u0026ge;\u0026thinsp;2 points were considered to have sepsis. Patients were eligible if they were 18 years of age or older, and at least 5 days of ICU stay, and availability of at least two serial CT datasets including the abdomen during hospitalization. We excluded patients if (1) they had creatinine\u0026thinsp;\u0026gt;\u0026thinsp;354umol/l on ICU admission, (2) received renal replacement therapy (RRT), (3) failed to match to complete data records, (4) transferred from another ICU, and (5) the interval between two serial CT datasets shorter than 5 days. The study was approved by the ethics committees of Zhongda Hospital, Southeast University (Number 2021ZDSYLL225-P01) and performed in accordance with STROBE \u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e guideline for observational research.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Data collection\u003c/h2\u003e \u003cp\u003eFor all patients, the following demographic and clinical data were collected from electronic health records: sex, age, height and weight, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE) II score, chronic comorbidities, admission diagnosis, and infection site. We recorded the creatine kinase, myoglobin, hemoglobin, albumin (ALB), prognostic nutritional indicators (PNI), blood glucose, lymphocyte count, procalcitonin (PCT), and lactate on day 1 after ICU admission. Urea nitrogen, and creatinine were extracted on day 1 and day 3. In addition, we collected the mode of nutritional support, daily caloric capacity, neuromuscular blockers use, Richmond agitation-sedation scale (RASS) score, and insulin dose. PNI was calculated as 10 \u0026times; serum ALB level (g/L)\u0026thinsp;+\u0026thinsp;0.005 \u0026times; total lymphocyte count (/mm3).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 L3 skeletal muscle area analysis\u003c/h2\u003e \u003cp\u003eCT images of the third lumbar vertebra (L3) were evaluated. For all patients included, skeletal muscle area at L3 slices (L3SMA) includes the psoas, erector spine, quadratus lumborum, transverse abdominous, external and internal obliques, and rectus abdominous. Images were analyzed by a trained specialist (J.J) with Image J software \u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e version 1.48 (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://imagej.nih.gov/ij/index.html\u003c/span\u003e\u003cspan address=\"https://imagej.nih.gov/ij/index.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e; NIH, Bethesda, MD, USA), which used predetermined thresholds (-29 to +\u0026thinsp;150 Hounsfield units) to demarcate skeletal muscle tissues \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Tissue boundaries were manually corrected if needed. L3SMA was calculated automatically by summing the skeletal muscle-tissue pixels and multiplying them by the surface area of each pixel. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the before and after changes in L3SMA (red) on transverse CT images in the same patient. L3SMA was adjusted by the square of the height (SMA/height2), which was referred to as the skeletal muscle index (L3SMI). L3SMI\u0026thinsp;=\u0026thinsp;L3SMA/ height 2. L3SMA was assessed on ICU admission and at least one more in-ICU follow-up CT. If the patient had more than twice upper abdominal CT scans during the ICU stay, only the first and second CT scan results were evaluated. According to previous research, in the first week of critical illness, patients lose approximately 2% of their muscle mass per day, so we define rapid muscle loss as △L3SMA\u0026thinsp;\u0026gt;\u0026thinsp;2% per day obtained from admission CT L3 muscle area and follow-up CT L3 muscle area\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e, as follows:\u003c/p\u003e \u003cp\u003e \u003cdiv id=\"Equa\" class=\"Equation\"\u003e \u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\:△\\:\\text{L}3\\text{S}\\text{M}\\text{A}=\\frac{\\text{a}\\text{d}\\text{m}\\text{i}\\text{s}\\text{s}\\text{i}\\text{o}\\text{n}\\:\\text{C}\\text{T}\\:\\text{L}3\\text{S}\\text{M}\\text{A}\\:-\\:\\:\\text{F}\\text{o}\\text{l}\\text{l}\\text{o}\\text{w}\\:\\text{u}\\text{p}\\:\\text{C}\\text{T}\\:\\text{L}3\\text{S}\\text{M}\\text{A}\\:}{\\text{a}\\text{d}\\text{m}\\text{i}\\text{s}\\text{s}\\text{i}\\text{o}\\text{n}\\:\\text{C}\\text{T}\\:\\text{L}3\\text{S}\\text{M}\\text{A}}$$\u003c/div\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Primary exposures and Outcomes\u003c/h2\u003e \u003cp\u003eThe primary exposures were UCR on day 1 (UCR_D1), which was calculated as [urea nitrogen*1000/ creatinine], UCR on day 3 (UCR_D3), and the difference in UCR between day 3 and day 1 (ΔUCR). The primary outcome was the incidence of rapid muscle loss during ICU hospitalization. The secondary outcomes included ICU and hospital length of stay, ICU mortality, 28-day mortality, hospital mortality, and ventilation-free days (VFDs) on day 28.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Statistical analysis\u003c/h2\u003e \u003cp\u003eValues are presented as the mean (standard deviation) or median [interquartile range (IQR)] for continuous variables as appropriate and as the total number (percentage) for categorical variables. Comparisons between rapid muscle loss and no rapid muscle loss patients were made using the X2 test or Fisher\u0026rsquo;s exact test for categorical variables and Student\u0026rsquo;s t-test or Mann-Whitney U test for continuous variables as appropriate.\u003c/p\u003e \u003cp\u003eWe first employed three multivariate logistic regression models to explore the association between UCR/ΔUCR and rapid muscle loss. Variables based on previous studies and clinical correlations including age, gender, BMI, SOFA score, Lactate, PCT, L3SMA, and PNI were entered into the model. We calculated the area under curve (AUC) of the receiver operating characteristic (ROC) curve to quantify the performance of UCR/ΔUCR in predicting rapid muscle loss. The optimal cut-off value of UCR/ΔUCR was determined by the Youden Index (sensitivity\u0026thinsp;+\u0026thinsp;specificity \u0026minus;\u0026thinsp;1). We also calculated the AUROCs after adjusting for the above confounders. The AUCs were compared by using the bootstrap test for each two ROC curves.\u003c/p\u003e \u003cp\u003eSeveral subgroup analyses were performed according to sex, age (\u0026ge;\u0026thinsp;60, \u0026lt;\u0026thinsp;60), Diabetes mellitus, BMI (\u0026ge;\u0026thinsp;24, \u0026lt;\u0026thinsp;24), SOFA score (\u0026ge;\u0026thinsp;8, \u0026lt;\u0026thinsp;8), PNI (\u0026ge;\u0026thinsp;34, \u0026lt;\u0026thinsp;34), L3SMI (\u0026ge;\u0026thinsp;40, \u0026lt;\u0026thinsp;40), use of mechanical ventilation, insulin, nutrition supports, neuromuscular blocker and vasopressor.\u003c/p\u003e \u003cp\u003eWe used Stata software version 15.0 (Stata Corp) and R software (IBM, Armonk, NY version 4.0.3) for all analyses. 2-tailed P\u0026thinsp;\u0026lt;\u0026thinsp;0 .05 was considered to be statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. RESULT","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n \u003ch2\u003e3.1 Baseline characteristics and clinical outcomes\u003c/h2\u003e\n \u003cp\u003eA total of 482 patients were included in the final analysis. The flow diagram of study patients was presented in Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. The median (IQR) age of the included patients was 62.0 (51.0, 74.0) years, with 350 males and 132 females (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Patients had a median SOFA score of 8 (6, 11) and a median APACHE II score of 19(14, 24). Among them, 141 patients (29.2%) had Rapid muscle loss during ICU stay. There was no significant difference in L3SMA between the two groups upon admission, and subsequently, L3SMA in both groups tended to decrease. However, the rapid muscle loss group showed a greater decrease in L3SMA, \u0026Delta; L3SMA is (20.65 [0.55], 14.54 [0.47], P\u0026thinsp;\u0026lt;\u0026thinsp;0.01) (Figure \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003e and Table \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003e). In CT re-examination within one week group, the decline rate was faster than in CT re-examination out of one week group (1.89 [0.87], 1.56 [0.56], P\u0026thinsp;\u0026lt;\u0026thinsp;0.01) (Table S2). Tables \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and S3 summarize the clinical characteristics of the rapid muscle loss group and the group without rapid muscle loss. Compared with the group without rapid muscle loss, patients with rapid muscle loss had a lower average age (56.00 [50.00, 71.00], 64.00 [51.00, 75.00], P\u0026thinsp;=\u0026thinsp;0.02), the proportion of male patients is higher (118 [83.69%], 232 [68%], P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), UCR-D3 and \u0026Delta; UCR significantly increased. There was no significant difference between the two groups in terms of 28-day mortality, ICU mortality, and length of hospitalization.\u003c/p\u003e\n \u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBaseline characteristics and clinical outcomes of patients. BMI, body mass index; APACHE II, acute physiology and chronic health evaluation II; SOFA, sequential organ failure assessment; UCR, urea-to-creatinine ratio; PCT, procalcitonin; RR, Respiratory rate; MAP, mean arterial pressure; L3SMA, skeletal muscle area at L3 slices; VFDs-28-day, mechanical ventilation free days to day28. * \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0 .05.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAll patients\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;482)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRapid\u0026nbsp;muscle loss\u003c/p\u003e\n \u003cp\u003egroup(N\u0026thinsp;=\u0026thinsp;141)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNon rapid\u0026nbsp;muscle loss group (N\u0026thinsp;=\u0026thinsp;341)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (year) (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.00 (51.00, 74.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56.00 (50.00, 71.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64.00 (51.00, 75.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.02*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e350 (72.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e118 (83.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e232 (68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInfection site\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRespiratory (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e295 (61.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81 (57.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e214 (62.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAbdominal (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e127 (26.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44 (31.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83 (24.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGenitourinary (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (2.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (2.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (2.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSkin/soft tissue (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (1.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (1.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBloodstream (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22 (4.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (4.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16 (4.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCentral nervous system (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (3.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (2.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (3.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOther (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (0.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (0.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.74 (21.72, 26.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.46 (22.86, 27.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.44 (20.96, 25.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAPACHE II (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.00 (14.00, 24.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.00 (13.00, 23.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.00 (14.00, 24.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSOFA (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.00 (6.00, 11.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.00(6.00, 11.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.00 (6.00, 11.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eShock (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e276 (57.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e157 (57.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e119 (56.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eComorbid conditions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypertension (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e213 (44.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52 (36.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e161 (47.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.04*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCoronary artery disease (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62 (12.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (9.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48 (14.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHeart failure (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60 (12.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (10.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45 (13.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic obstructive pulmonary disease (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27 (5.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (5.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19 (5.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes mellitus (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e119 (24.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33 (23.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86 (25.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSolid malignant tumors (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71 (14.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (9.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57 (16.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHematologic cancer (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (1.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (1.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCirrhosis (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (1.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (1.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (1.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOther (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (2.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (2.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (2.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAdmission vital signs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTemperature (\u0026deg;C) (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37.2 (36.5, 38.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37.4 (36.5, 38.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37.2 (36.5, 38.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRR (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(12, 28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20(12, 28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(13, 28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHeart rate (beats/min) (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e111(73, 126)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e111(80, 125)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e111(72, 127)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.90\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMAP (mmHg) (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.00 (71.00, 78.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.00 (72.00, 78.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.00 (70.00, 78.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAdmission blood tests (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCreatinine (umol/L) (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78.00 (59, 107)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e82.00 (63, 109)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.00 (56, 103)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUrea (umol/L) (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6900(4700, 10400)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6800 (5100, 9200)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6900(4600, 10700)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUrea: creatinine (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88.55 (61.42, 123.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e84.21 (62.50, 110.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92.50 (61.43, 132.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.02*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLactate (mmol/L) (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.60 (1.10, 2.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.50 (1.10, 2.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.60 (1.10, 2.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePCT (ng/ml) (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.89 (0.14, 4.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.02 (0.2, 3.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.88 (0.13, 5.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlbumin (g/L) (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.20 (27.00, 34.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.90 (27.00, 33.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.20 (26.90, 34.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLymphocyte count (\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L) (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.70 (0.47, 1.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.74 (0.52, 1.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.69 (0.46, 1.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHemoglobin (g/L) (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e106.00 (91.00, 123.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e105.00 (89.00, 125.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e106.00 (92.00, 122.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAdmission L3SMA (cm\u003csup\u003e2\u003c/sup\u003e) mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e118.96 (32.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e141.66 (30.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e109.58 (28.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHospital length of stay (day) (mean [SD])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31.40 (20.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.82 (17.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32.47 (21.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.08*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eICU length of stay (day) (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16 (11, 26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (10, 24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (11,26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHospital mortality (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e105 (21.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24 (17.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81 (23.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eICU mortality (n) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92 (19.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20 (14.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72 (21.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28-day mortality (day) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76 (15.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (14.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55 (16.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlive and VFDs-28-day (day) (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.35 (7.56141)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.46 (7.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.3 (7.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003eIn addition, a separate analysis of 176 patients who underwent CT re-examination within one week revealed that 67 patients (38.1%) had rapid muscle loss. There was no significant difference in 28-day mortality or ICU mortality between patients with and without rapid muscle loss, but the length of hospitalization was longer than in patients without rapid muscle loss (28.5 [2.1], 21.9 [1.16], P\u0026thinsp;\u0026lt;\u0026thinsp;0.01) (Table S4).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003eBMI, body mass index; APACHE II, acute physiology and chronic health evaluation II; SOFA, sequential organ failure assessment; UCR, urea-to-creatinine ratio; PCT, procalcitonin; RR, Respiratory rate; MAP, mean arterial pressure; L3SMA, skeletal muscle area at L3 slices; VFDs-28-day, mechanical ventilation free days to day28. * \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0 .05.\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n \u003ch2\u003e3.2 Association between UCR and rapid muscle loss\u003c/h2\u003e\n \u003cp\u003eThe multivariate logistic regression analysis showed that UCR_D1 and UCR_D3 were not associated with an increased risk of rapid muscle loss, while there was a significant association between \u0026Delta;UCR and rapid muscle loss, with an OR of 1.02 [95% CI: 1.01,1.02] (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). The comparisons were similiar after adjusing for confounders.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMultivariate logistic regression exploring the impact of UCR on the risk of rapid muscle loss.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"7\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAdjusted for UCR_D1\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAdjusted for UCR_D3\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAdjusted for \u0026Delta;UCR\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99 (0.97,1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.03*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99 (0.99,1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.02*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99 (0.99,0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.02*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.95 (0.58,1.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99 (0.61,1.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.95 (0.58,1.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.96 (0.89,1.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.96 (0.90,1.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.96 (0.89,1.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSOFA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99 (0.94,1.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99 (0.93,1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99 (0.94,1.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eL3SMA on Day 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 (0.99,1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 (0.99,1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 (0.98,1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLactate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 (0.92,1.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.02 (0.93,1.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 (0.91,1.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.98 (0.95,1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.98 (0.95,1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.98 (0.95,1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePNI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99 (0.97,1.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99 (0.97,1.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99 (0.68,1.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUCR_D1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 (0.99,1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUCR_D3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 (0.99,1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026Delta;UCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.02 (1.01,1.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eThe reference group was non rapid muscle loss. OR, odds ratio; CI, Confidence interval; SOFA, sequential organ failure assessment; BMI, body mass index; PCT, procalcitonin; PNI, prognostic nutritional index; L3SMA, skeletal muscle area at L3 slices; UCR, urea-to-creatinine ratio; UCR_D1, urea-to-creatinine ratio on day1; UCR_D3, urea-to-creatinine ratio on day3; \u0026Delta;UCR, difference in UCR between day 3 and day 1. *: \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0 .01.\u003c/p\u003e\n \u003cp\u003eIn patients who underwent CT re-examination within one week, \u0026Delta;UCR is still associated with rapid muscle loss (Table S5). Analysis of the predictive values of UCR_D1, UCR_D3 and \u0026Delta;UCR for rapid muscle loss showed that UCR_D1 and UCR_D3 had poor predictive accuracy (AUROC 0.46 and 0.57). \u0026Delta;UCR had the highest predictive accuracy (AUROC 0.76) (Figure. 3). \u0026Delta;UCR had an optimal threshold of 19.4 for the prediction of rapid muscle loss, with sensitivity and specificity of 60% (49\u0026ndash;83) % and 84% (61\u0026ndash;95) %, respectively. The positive predictive value was 70% (67\u0026ndash;93) % and the negative predictive value was 77% (68\u0026ndash;85) %. The Youden index was 0.44 (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab6\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe accuracy of UCR to predict rapid muscle loss in CT re-examination within one week group. AUROC, area under the receiver operating characteristic; UCR, urea-to-creatinine ratio; UCR_D1, urea-to-creatinine ratio on day1; UCR_D3, urea-to-creatinine ratio on day3; \u0026Delta;UCR, difference in UCR between day 3 and day 1.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"7\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAUROC\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eThreshold\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSensitivity, %\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSpecifcity, %\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePositive predictive value, %\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNegative predictive value, %\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUCR_D1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.46 (0.37\u0026ndash;0.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.88 (0.76\u0026ndash;0.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.17 (0.12\u0026ndash;0.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.39 (0.31\u0026ndash;0.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.68 (0.52\u0026ndash;0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUCR_D3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.57 (0.49\u0026ndash;0.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;70.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.84 (0.49\u0026ndash;0.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.37 (0.29\u0026ndash;0.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.45(0.36\u0026ndash;0.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.78 (0.69\u0026ndash;0.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026Delta;UCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.76 (0.68\u0026ndash;0.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;19.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.60 (0.49\u0026ndash;0.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.84 (0.61\u0026ndash;0.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.70 (0.67\u0026ndash;0.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.77 (0.68\u0026ndash;0.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eAUROC, area under the receiver operating characteristic; UCR, urea-to-creatinine ratio; UCR_D1, urea-to-creatinine ratio on day1; UCR_D3, urea-to-creatinine ratio on day3; \u0026Delta;UCR, difference in UCR between day 3 and day 1.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003e3.3 Subgroup analyses\u003c/h2\u003e\n \u003cp\u003eRegardless of the subgroup, \u0026Delta;UCR was associated with a higher probability of rapid muscle loss. No significant differences were observed among the subgroups. However, subgroup analysis in patients who underwent CT re-examination within one week showed that in the age subgroup, the AUROC of rapid muscle loss predicted by \u0026Delta; UCR was significantly higher in patients aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years than in patients aged\u0026thinsp;\u0026lt;\u0026thinsp;60 years (0.82 [95% CI 0.74\u0026ndash;0.91] vs. 0.67 [95% CI 0.55\u0026ndash;0.79], P\u0026thinsp;=\u0026thinsp;0.04). In the nutritional support subgroup, the AUROC of rapid muscle loss predicted by \u0026Delta; UCR was significantly higher in patients without nutritional support than in patients with nutritional support (0.79 [95% CI 0.72\u0026ndash;0.87 vs 0.58 [95% CI 0.39\u0026ndash;0.78], P\u0026thinsp;=\u0026thinsp;0.04) (Table S6 and Figure S2).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"4. DISCUSSION","content":"\u003cp\u003eIn this study, we found that 29.2% of patients experienced rapid muscle loss during their ICU stay. The rate of decline was faster in the early stages of ICU (within a week) than in the later stages. Patients who showed rapid muscle loss within one week of ICU admission had longer hospitalization. UCR was confirmed to be independently associated with rapid muscle loss by analyzing patients' abdominal CT scans and biochemical markers.\u003c/p\u003e \u003cp\u003eAn early elevated UCR helped predict the development of rapid muscle loss. in patients with sepsis. The pronounced muscle wasting that contributed to the weakness of myogenic origin in sepsis patients was explained by the catabolic state of critical illness, with decreased anabolic effector hormones and increased catabolic hormones \u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e, as well as the mechanical unloading brought on by immobilization or denervation. This metabolic disorder led to an increase in protein catabolism and a decrease in anabolism \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Increased protein catabolism led to increased urea production, and increased catabolism brought about a decrease in total muscle mass and a decrease in creatinine levels; which eventually increased UCR. Therefore, an early increase in the UCR would help predict the occurrence of rapid muscle loss in sepsis patients. Haines reported \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e that in patients after major trauma with ICU stay\u0026thinsp;\u0026ge;\u0026thinsp;10 days, UCR on day 10 had increased by 133%. Elevated UCR was a biochemical marker indicating persistent critical illness after major trauma and was seen in association with the wasting of skeletal muscle. In other investigations on nutrient metabolism, the UCR had also been found to be a usable clinical biomarker of muscle catabolism conditions in critical diseases \u003csup\u003e[\u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWe conducted a separate analysis on patients who underwent CT re-examination within one week of staying in the ICU. The results showed that early increase in the UCR had a higher accuracy in predicting rapid muscle loss in CT re-examination within one week group. This result can be explained in subgroup analysis. Subgroup analysis showed that the implementation of enteral nutrition would reduce the value of UCR in predicting rapid muscle loss. With the extension of ICU stay time, including the implementation of nutritional support and protein intake, the body has shifted from early catabolism to a complex state of coexistence of catabolism and synthetic metabolism, masking the early protein metabolism disorder in sepsis patients. Therefore, the predictive value of UCR as a marker reflecting protein breakdown metabolism will decrease.\u003c/p\u003e \u003cp\u003eCritically ill patients may develop rapid muscle loss as early as the day after admission to ICU \u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e, and the incidence increases as the length of ICU stay increases. 24%-55% of patients develop ICUAW when the length of ICU stays is extended to 5\u0026ndash;7 days, and the incidence can further increase to 75% \u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e when the length of ICU stay exceeds 10 days. The incidence of rapid muscle loss of critically ill patients with sepsis in this study is similar to that in the above studies. In terms of prognosis, we discovered that in the rapid muscle loss group patients had longer hospital stays, which is consistent with other relevant studies \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Previous studies \u003csup\u003e[13\u0026ndash;14,32\u0026minus;34]\u003c/sup\u003e have shown that rapid muscle loss affects not only the short-term prognosis of patients but also the long-term quality of survival after discharge; yet, the present study failed to follow up on the long-term prognosis of the patients.\u003c/p\u003e \u003cp\u003eThe study has several limitations. First, the effects of rapid muscle loss on long-term survival and quality of survival were not evaluated. Second, patients who underwent RRT were excluded from this study because it was considered that the removal of urea and creatinine by RRT would interfere with the study results, which may lead to population bias. Third, this study only evaluated muscle loss and did not assess changes in patient muscle strength, so it cannot be determined whether the patient has developed ICUAW. Finally, this was a retrospective observational study, and no clear causal conclusion could be drawn.\u003c/p\u003e"},{"header":"5. CONCLUSION","content":"\u003cp\u003eApproximately one-third (29.2%) of critically ill patients with sepsis will experience rapid muscle loss. Elevated UCR is independently associated with rapid muscle loss, and it can predict rapid muscle loss in sepsis patients. UCR provides a simple bedside marker for early identification and intervention of rapid muscle loss.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCT：computed tomography; ICUAW：Intensive care unit-acquired weakness; SOFA：sequential organ failure score; RRT：renal replacement therapy; UCR：urea-to-creatinine ratio; \u0026Delta;UCR d3-d1：UCR on day 3 minus UCR on day 1; \u0026Delta;UCR d5-d1： UCR on day 5 minus UCR on day 1; SMI：skeletal muscle index; L3：third lumbar spine; L3SMA：skeletal muscle area at the third lumbar vertebra slices; L3SMI：skeletal muscle index at the third lumbar vertebra slices; APACHE II: Acute Physiology and Chronic Health Evaluation II; ICU: Intensive care unit; LOS: Length of stay; IQR: Interquartile range; OR: Odds ratio; PCT：procalcitonin; PNI：prognostic nutritional indicators; RASS score：Richmond Agitation-Sedation Scale score; CRP：C-reactive protein; BMI：Body Mass Index; VFDs：mechanical ventilation free days; AUROC：area under the receiver operating characteristic; CI：confidence interval.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval\u003c/strong\u003e \u003cp\u003e This study was approved by the Ethics Committees for Clinical Research of Zhongda Hospital, Southeast University (Number 2021ZDSYLL225-P01). All participants or their legal representatives have signed informed consent. The study complied with the Declaration of Helsinki and its amendments.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eF.G.: Designed the study. J.J.:Writing a manuscript. J.X., P.C. and H.C.: Assist in editing and reviewing manuscripts. S.M.: Help for data collection and analysis. All authors have contributed to the article and agree to the submitted version.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eAvailability of data\u003c/h2\u003e \u003cp\u003eThe datasets generated and analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePuthucheary ZA, et al. Acute skeletal muscle wasting in critical illness. JAMA. 2013;310(15):1591\u0026ndash;600.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDerde S, et al. Muscle atrophy and preferential loss of myosin in prolonged critically ill patients. Crit Care Med. 2012;40(1):79\u0026ndash;89.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLooijaard WGPM, Molinger J, Weijs PJM. Measuring and monitoring lean body mass in critical illness. Curr Opin Crit Care. 2018;24(4):241\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWieske L, et al. Neurofilaments as a plasma biomarker for ICU-acquired weakness: An observational pilot study. Crit Care. 2014;18:1\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGunst J, et al. Impact of early parenteral nutrition on metabolism and kidney injury. J Am Soc Nephrol. 2013;24(6):995\u0026ndash;1005.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGomez-Perez SL, et al. Measuring Abdominal Circumference and Skeletal Muscle From a Single Cross-Sectional Computed Tomography Image: A Step-by-Step Guide for Clinicians Using National Institutes of Health ImageJ. JPEN J Parenter Enter Nutr. 2016;40(3):308\u0026ndash;18.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchefold JC, Bierbrauer J, Weber-Carstens S. Intensive care unit-acquired weakness (ICUAW) and muscle wasting in critically ill patients with severe sepsis and septic shock. J Cachexia Sarcopenia Muscle. 2010;1(2):147\u0026ndash;57.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThille AW, et al. Role of ICU-acquired weakness on extubation outcome among patients at high risk of reintubation. Crit Care. 2020;24(1):86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShepherd SJ, Newman R, Brett SJ, Griffith DM. Enhancing rehabilitation after critical illness programme study investigators. Pharmacological therapy for the prevention and treatment of weakness after critical illness: A systematic review. Crit Care Med. 2016;44(6):1198\u0026ndash;205.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVanhorebeek I, Latronico N, Van den Berghe G. ICU-acquired weakness. Intensive Care Med. 2020;46(4):637\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSoares MN, et al. Skeletal muscle alterations in patients with acute Covid-19 and post-acute sequelae of Covid-19. J Cachexia Sarcopenia Muscle. 2022;13(1):11\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMenges D, et al. Systematic early versus late mobilization or standard early mobilization in mechanically ventilated adult ICU patients: systematic review and meta-analysis. Crit Care. 2021;25(1):16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKress JP. Hall JB.ICU-acquired weakness and recovery from critical illness. N Engl J Med. 2014;370(17):1626\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan Aerde N, et al. Five-year impact of ICU-acquired neuromuscular complications: a prospective, observational study. Intensive Care Med. 2020;46(6):1184\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmini B, Boyle SP, Boutin RD, Lenchik L. Approaches to Assessment of Muscle Mass and Myosteatosis on Computed Tomography: A Systematic Review. J Gerontol Biol Sci Med Sci. 2019;74:1671\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim KM, Jang HC, Lim S. Differences among skeletal muscle mass indices derived from height-, weight-, and body mass index-adjusted models in assessing sarcopenia. Korean J Intern Med. 2016;31:643\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchweitzer L, et al. What is the best reference site for a single MRI slice to assess whole-body skeletal muscle and adipose tissue volumes in healthy adults? Am J Clin Nutr. 2015;102:58\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYip C, et al. Imaging body composition in cancer patients: visceral obesity, sarcopenia and sarcopenic obesity may impact on clinical outcome. Insights Imaging. 2015;6:489\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGunst J, et al. Impact of early parenteral nutrition on metabolism and kidney injury. J Am Soc Nephrol. 2013;24(6):995\u0026ndash;1005.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaines RW, et al. Elevated UCR provides a biochemical signature of muscle catabolism and persistent critical illness after major trauma. Intensive Care Med. 2019;45(12):1718\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSeymour CW, et al. Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):762\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVon Elm E, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGomez-Perez SL, et al. Measuring Abdominal Circumference and Skeletal Muscle From a Single Cross-Sectional Computed Tomography Image: A Step-by-Step Guide for Clinicians Using National Institutes of Health ImageJ. JPEN J Parenter Enter Nutr. 2016;40(3):308\u0026ndash;18.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFazzini B, et al. The rate and assessment of muscle wasting during critical illness: a systematic review and meta-analysis. Crit Care. 2023;27(1):2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVankrunkelsven W, et al. Obesity attenuates inflammation, protein catabolism, dyslipidaemia, and muscle weakness during sepsis, independent of leptin. J Cachexia Sarcopenia Muscle. 2022;13(1):418\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan den Berghe G. On the neuroendocrinopathy of critical illness. perspectives for feeding and novel treatments. Am J Respir Crit Care Med. 2016;194(11):1337\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFlower L, et al. Effect of intermittent or continuous feeding and amino acid concentration on UCR in critical illness. JPEN J Parenter Enter Nutr. 2022;46(4):789\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePage A, Flower L, Prowle J, Puthucheary Z. Novel methods to identify and measure catabolism. Curr Opin Crit Care. 2021;27(4):361\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaines RW, et al. Catabolism in Critical Illness: A Reanalysis of the REducing Deaths due to OXidative Stress (REDOXS) trial. Crit Care Med. 2022;50(7):1072\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTennil\u0026auml; A, et al. Early signs of critical illness polyneuropathy in ICU patients with systemic inflammatory response syndrome or sepsis. Intensive Care Med. 2000;26(9):1360\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePaolo F, et al. The possible predictive value of muscle ultrasound in the diagnosis of ICUAW in long-term critically ill patients. J Crit Care. 2022;71:154104.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Jonghe B, et al. Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA. 2002;288(22):2859\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eViertel M, Bock C, Reich M, L\u0026ouml;ser S, Plauth M. Performance of CT-based low skeletal muscle index, low mean muscle attenuation, and bioelectric impedance derived low phase angle in the detection of an increased risk of nutrition related mortality. Clin Nutr. 2019;38(5):2375\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eToledo DO, et al. The use of computed tomography images as a prognostic marker in critically ill cancer patients. Clin Nutr ESPEN. 2018;25:114\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Sepsis, skeletal muscle wasting, Urea-to-creatinine ratio, ICU acquired weakness","lastPublishedDoi":"10.21203/rs.3.rs-5239381/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5239381/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eSepsis patients in the ICU often experience rapid muscle loss. Urea-to-creatinine ratio (UCR) reflects protein metabolism and is often used to assess nutritional metabolic status. This study aimed to investigate whether the UCR can predict the development of rapid muscle loss in patients with sepsis.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eOur retrospective observational study was performed in a university ICU from 2014 to 2021 on adult (\u0026ge;\u0026thinsp;18 years) sepsis patients. The primary outcome was the incidence of rapid muscle loss during ICU hospitalization. We utilized multivariate logistical regression to characterize the association between UCR/ΔUCR and rapid muscle loss. The area under curve (AUC) of the receiver operating characteristic (ROC) curve was calculated to quantify the performance of UCR/ΔUCR in predicting rapid muscle loss.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong all 482 patients, 141 patients (29.2%) had rapid muscle loss during ICU stay. Multivariate logistic regression analysis showed that ΔUCR was associated with an increased risk of rapid muscle loss, the Odds ratio was 1.02 [95% CI: 1.01,1.02]. The predictive ability of ΔUCR for rapid muscle loss was 0.76[95% CI 0.68\u0026ndash;0.83]. The threshold was 19.4 for ΔUCR.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOur findings show that elevated UCR is independently associated with rapid muscle loss, and it can predict rapid muscle loss in sepsis patients. UCR provides a simple bedside marker for early identification and intervention of rapid muscle loss.\u003c/p\u003e","manuscriptTitle":"Early urea-to-creatinine ratio to predict rapid muscle loss in critically ill patients with sepsis: a retrospective observational study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-16 05:42:29","doi":"10.21203/rs.3.rs-5239381/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-10-14T17:02:22+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-12T06:01:11+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-12T05:59:12+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Anesthesiology","date":"2024-10-10T11:48:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ae64a021-d0b3-4c3a-a4a1-155b664c81f3","owner":[],"postedDate":"December 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-01-13T16:04:22+00:00","versionOfRecord":{"articleIdentity":"rs-5239381","link":"https://doi.org/10.1186/s12871-025-02892-8","journal":{"identity":"bmc-anesthesiology","isVorOnly":false,"title":"BMC Anesthesiology"},"publishedOn":"2025-01-11 15:57:57","publishedOnDateReadable":"January 11th, 2025"},"versionCreatedAt":"2024-12-16 05:42:29","video":"","vorDoi":"10.1186/s12871-025-02892-8","vorDoiUrl":"https://doi.org/10.1186/s12871-025-02892-8","workflowStages":[]},"version":"v1","identity":"rs-5239381","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5239381","identity":"rs-5239381","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}