Monitoring Neutrophil-to-Lymphocyte Ratio Dynamics for Personalized Treatment in Adolescent Eating Disorders: A retrospective cohort study

Monitoring Neutrophil-to-Lymphocyte Ratio Dynamics for Personalized Treatment in Adolescent Eating Disorders: A retrospective cohort 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 correspondence Monitoring Neutrophil-to-Lymphocyte Ratio Dynamics for Personalized Treatment in Adolescent Eating Disorders: A retrospective cohort study Yuta Inagawa, Kazumi Kurata, Seiji Obi, Yoshiyuki Onuki, Yukihumi Monden, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5919028/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 19 May, 2025 Read the published version in Journal of Eating Disorders → Version 1 posted 7 You are reading this latest preprint version Abstract Objective This study aimed to evaluate the dynamics of the neutrophil-to-lymphocyte ratio (NLR) during the initial hospitalization of patients with eating disorders (EDs) and to assess its potential as a biomarker for monitoring disease severity and treatment response. Methods A retrospective chart review was conducted with 55 patients aged ≤ 16 years diagnosed with anorexia nervosa or avoidant/restrictive food intake disorder and admitted to Jichi Medical University Hospital between 2015 and 2021. Sociodemographic and clinical characteristics including sex, age, rate of weight gain, percentage of ideal body weight (%IBW), tube feeding treatment, and NLR were obtained. Statistical analyses used a mixed model for repeated measures to assess NLR changes regarding %IBW and other clinical factors. Results The NLR at admission was lower in the malnourished state but increased with weight recovery. MMRM revealed that tube feeding treatment and restoration of %IBW significantly predicted an increase in the NLR. The interaction between tube feeding and the quadratic term of %IBW was also significant, indicating distinct patterns of NLR changes: without tube feeding, NLR increased linearly with weight recovery, whereas with tube feeding, NLR exhibited a non-linear, upward-convex parabolic trend. Discussion These findings indicate that NLR may serve as a potential biomarker for monitoring recovery in patients with EDs, reflecting nutritional status and tube feeding-related factors. NLR measurement could be a practical tool for tailoring treatment strategies. Further research is warranted to explore NLR's utility across diverse ED populations and assess its responsiveness to various interventions, advancing personalized medicine in this field. neutrophil-to-lymphocyte ratio eating disorders tube feeding nutritional status ideal body weight Figures Figure 1 Introduction Eating disorders (EDs), psychiatric conditions manifesting in adolescence, lack established biomarkers for diagnosis or treatment. EDs involve significant disruptions in eating behaviors, leading to medical and psychological complications. Diagnosis is clinically assessed using operational diagnostic criteria, which include weight changes and symptoms, with the Diagnostic and Statistical Manual of Mental Disorders, 5th ed., as an example. [ 1 ]. Therapists should also consider ancillary biomarkers such as hormones, neuroimaging, and re-feeding markers [ 2 ], though repeating these during treatment is cost-prohibitive. Unlike other psychiatric conditions, EDs are influenced by starvation and malnutrition, complicating the use of biomarkers for other mental health disorders [ 3 ]. Since the heterogeneity of EDs poses challenges in evaluating recovery based on single indicators, such as weight or psychopathological findings, a comprehensive assessment that incorporates multiple related factors could better capture the complexity of recovery. Developing a multimodal predictive model integrating such factors would be clinically valuable for improving personalized treatment and monitoring outcomes in patients with EDs. Recently, the neutrophil-to-lymphocyte ratio (NLR) has gained attention as a biomarker for psychiatric disorders [ 4 ]. The NLR, derived from routine blood tests, is the ratio of neutrophils to lymphocytes. Neutrophils indicate innate immunity through inflammatory factors, whereas lymphocytes represent adaptive immunity, with low counts indicating compromised health and stress [ 5 ]. Elevated NLR is associated with acute episodes and disease severity in various adolescent psychiatric conditions [ 6 – 14 ]. However, in EDs, particularly anorexia nervosa (AN), NLR behaves differently [ 15 – 17 ]. Studies have shown that NLR decreases during acute AN, reflecting the body’s starvation response [ 16 , 17 ]. As patients recover, the NLR increases, indicating an improved nutritional and inflammatory status. NLR dynamics during ED treatment and their correlation with clinical features remain underexplored. This study evaluated NLR trajectories in adolescent ED patients during initial hospitalization to assess their potential as biomarkers. We retrospectively analyzed NLR fluctuations in patients hospitalized for their first ED episode, associating these changes with clinical characteristics to determine NLR's reliability for monitoring disease severity and treatment response. Materials and Methods A retrospective chart review was conducted with all patients admitted to the psychiatric ward of Jichi Medical University Hospital Tochigi Children's Medical Center between January 1, 2015, and December 31, 2021. The diagnosis was verified by two trained child psychiatrists based on the DSM-5 criteria for AN or avoidant/restrictive feeding and intake disorder (ARFID). Participants and inpatient treatment This study included children with AN or ARFID who received initial inpatient ED treatment. The exclusion criteria were as follows: (i) age over 16 years, (ii) admission weight over 85% of ideal body weight (%IBW), and (iii) inability to measure the NLR at least twice. Inpatient treatment occurred in a closed child psychiatry ward managed by a multidisciplinary team of 3–4 child psychiatrists, psychologists, nurses, psychiatric social workers, and dieticians. This approach included establishing therapeutic relationships, diagnosis, assessment, psychoeducation, nutritional guidance, food records, re-nutritional therapy using behavioral techniques, and supportive psychotherapy. Psychiatrists met patients at least three times a week to discuss treatment plans, with periodic family interviews to share progress. Nurses provided dietary and lifestyle care and explained the disease stages. The psychologists conducted individual and group therapy sessions. Psychiatric social workers liaised with schoolteachers and offered social support for future school reintegration. Dietitians offered nutritional guidance. Re-nutritional therapy primarily involved oral nutrition with tube feeding if necessary. Measurements Sociodemographic and clinical characteristics This study aimed to evaluate NLR dynamics in the inpatient treatment process and its association with sociodemographic and clinical characteristics. We examined the participants’ sociodemographic and clinical characteristics to identify potential confounding factors: age at admission, sex, classification of eating disorders (AN, ARFID), duration of hospital stay, %IBW on admission, %IBW at discharge, rate of weight gain (kg/week), and gastric tube feeding. Percentage of ideal body weight (%IBW) %IBW was calculated via a formula (patient weight × 100/standard weight), where the standard weight was determined by the Japan Pediatric Endocrine Society’s criteria [ 18 ]. Patients with < 85%IBW were defined as having low body weight according to the Hirata method commonly used in Japan to evaluate pediatric physiques. Statistical analysis Statistical analysis examined the correlation between changes in NLR and other variables. NLRs at ≥ 38°C were excluded because of potential infectious disease effects. A paired t-test was used to compare %IBW at admission and discharge. Given the expected non-linear relationship between NLR and %IBW influenced by physical and psychological stress during inpatient treatment, a quadratic term for %IBW (%IBW²) was included in a mixed model for repeated measures analysis. To prevent multicollinearity between %IBW and %IBW², %IBW was centered using grand-mean centering. A random slope model was used for %IBW to account for individual variations in its effect on NLR. All analyses were performed with R software (version 4.4.1), and graphs were created using RStudio (2024.04.2 + 764). Results In this study, 76 patients were admitted to our hospital for treatment of eating disorders. Among them, two, three, and 16 were excluded because they were older, overweight, and had <2 NLR measurements, respectively. A total of 55 patients were included in the study (Figure 1). The clinical characteristics of the patients are shown in Table 1. A paired t-test revealed that %IBW was significantly higher at discharge than at admission ( p < 0.01, data not shown). Table 2 presents the findings of the mixed model for repeated measures (MMRM) and identifies several predictors of NLR variability. Model 1 was fitted to examine the effects of tube feeding treatment, age in months, %IBW, %IBW 2 , rate of weight gain (kg/week), gender, and diagnosis (AN or ARFID) on the NLR. Fixed effects estimates indicated that tube feeding had a statistically significant effect (β = 0.538, p = 0.007), with higher NLR values observed in the tube feeding group. The effect of the %IBW was statistically significant (β = 0.029, p <. 0.001). %IBW 2 was also significant (β = -0.001, p = 0.003), indicating a non-linear relationship between %IBW and NLR, characterized by an upward-convex parabolic trend. To investigate the interactions between tube feeding and %IBW, variables that were statistically significant in model 1 were included in model 2. No interaction was found between tube feeding and %IBW, but an interaction emerged between tube feeding and %IBW² (β = -0.002, p = 0.013), indicating that the NLR increased linearly without tube feeding and non-linearly with tube feeding, following an upward-convex parabolic trend. Random effects analysis revealed a standard deviation of 0.524 for random intercepts, which indicated variability in the baseline NLR among individuals. The standard deviation for the random slopes of %IBW 2 was 0.021, which suggests minimal variability in the effect of %IBW on the NLR. Discussion Changes in NLR in adolescent ED patients during inpatient treatment indicated that body weight recovery was crucial for restoring NLR values. As body weight increased, NLR values progressively normalized, highlighting the importance of physical health in stabilizing inflammatory markers. MMRM analysis showed a linear NLR increase without tube feeding, reflecting gradual recovery with weight gain, and a nonlinear, upward-convex trend with tube feeding, suggesting accelerated weight gain but additional stressors affecting the NLR. The initial NLR values varied significantly among participants; however, the impact of %IBW on NLR was consistent, regardless of the initial NLR values. This indicates that weight restoration is essential for improving NLR values, irrespective of the baseline immune status or social background, as evidenced by the upward NLR trend during treatment. A previous study reported that NLR tended to decrease during the acute phase of EDs, particularly AN, owing to decreased muscle mass, bone marrow activity, adiponectin levels, and cachexia [ 16 , 17 ]. Our findings align with this, as the NLR values at admission were lower in malnourished patients. Importantly, as body weight improved during treatment, the NLR values also showed significant recovery, highlighting the interdependence of nutritional status and immune function. Tube feeding treatment in patients with EDs can elevate NLR, likely owing to both physical and psychological stress. The use of tube feeding in the treatment of EDs has been associated with shorter hospital stays and increased caloric intake, which can facilitate faster weight restoration [ 19 ]. Although generally considered safe, side effects, such as nasal irritation, epistaxis, and anxiety, are common. In some cases, physical restraint may be required; however, our study had no cases that required physical restraint. Additionally, tube feeding treatment may provoke feelings of fear or loss of control due to passive nutritional intake and faster weight restoration [ 20 ], potentially contributing to an elevated inflammatory response. Furthermore, the apparent elevation in NLR may have been due to physical irritation and mechanical stimulation associated with tube feeding, rather than reflecting true improvements in the underlying condition, because NLR tended to decrease in the late phase of inpatient treatment with tube feeding. This may reflect the impact of gastric tube removal. Therefore, careful monitoring of changes in NLR after discontinuation of tube feeding is crucial to better understand its true implications and to ensure that NLR dynamics genuinely indicate recovery rather than transient stress responses. In this study, we examined NLR as a potential biomarker for evaluating recovery in patients with EDs. However, the complexity and heterogeneity of EDs necessitate a broader approach for recovery assessment [ 3 ]. Future research should incorporate a diverse range of variables, including clinical, biochemical, nutritional, and psychological factors into a unified predictive framework. The integration of these factors would provide a more holistic understanding of recovery dynamics and allow more nuanced assessments tailored to individual patients. Moreover, leveraging advanced methodologies such as machine learning and artificial intelligence could facilitate the development of robust multimodal predictive models. These models would not only improve the accuracy of recovery predictions but also support the implementation of personalized treatment strategies and optimize interventions for specific patient profiles. By addressing the multifaceted nature of EDs, this approach has the potential to significantly enhance the clinical utility and outcomes. This study has several limitations. First, as a retrospective analysis, the frequency of NLR measurements decreased during later hospitalization, limiting the assessment of long-term NLR trends. Second, childhood maltreatment, which could influence NLR, was not evaluated. Future studies should assess patients' psychosocial backgrounds to better understand the impact of trauma on NLR fluctuations. Third, differences in tube feeding usage, including duration and methods, and the psychological effects of tube feeding were not considered. Fourth, tube feeding might have triggered hyperactivity in some patients, potentially elevating the neutrophil counts and NLR. This confounder was not assessed and requires further investigation. Future studies should examine the impact of psychosocial factors on immune function and explore the potential influence of tube feeding on inflammatory markers. In this study, the NLR was highlighted as a component of a potential multimodal recovery index. As a quantitative metric, NLR offers valuable insights; however, future studies should aim to incorporate a variety of data types, including other quantitative measures and possibly non-quantitative data, such as imaging. This study advances personalized treatment in EDs by developing a more comprehensive recovery index. Abbreviations AN Anorexia Nervosa ARFID Avoidant/restrictive feeding and intake disorder DSM-5 Diagnostic and statistical manual of mental disorders. 5th ed. EDs Eating disorders ICD-10 International statistical classification of diseases and related health problems, 10th Revision MMRM Mixed model for repeated measures NLR Neutrophil-to-lymphocyte ratio %IBW Percentage of ideal body weight Declarations Ethics approval and consent to participate This study received approval from the Ethics Review Committee of Jichi Medical University. Consent was obtained via an opt-out method, with information provided through documents posted on the websites of the Departments of Psychiatry and Children's Mental Health at Jichi Medical University, ensuring participants were adequately informed. Consent for publication This study was conducted as a retrospective chart review. Participation was based on an opt-out method, whereby eligible patients and their guardians were informed of the study through documents posted on the website of the Departments of Psychiatry and Children's Mental Health at Jichi Medical University. Individuals who did not wish to participate were given the opportunity to express their decision to opt out. As no personal identifiable information is included in this publication, additional written consent for publication was not required. Availability of data and materials The data that support the findings of this study are available from Jichi Medical University but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Jichi Medical University. Competing interests The authors have no financial or nonfinancial interests to disclose. Paperpal was used solely for grammar checks to enhance readability, not for text generation. All authors reviewed and edited the manuscript and assume full responsibility for its publication. Funding This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI, Grant Number JP80382951. Author Contributions Y.I. and T.Y. designed the study. Y.I., K.K. (Kurata), S.O., K.K. (Kurane), R.F., T.M., and H.N. collected the data. Y.M. provided financial support. Y.I., Y.O., T.Y., and S.S. prepared the original draft. Y.O. and T.Y. provided statistical analyses supports. All authors have read and agreed to the published version of the manuscript. Acknowledgement We would like to thank Editage (www.editage.jp) for English language editing. References American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013. Himmerich H, Treasure J. Anorexia nervosa: diagnostic, therapeutic, and risk biomarkers in clinical practice. Trends Mol Med. 2024;30(4):350–360. doi:10.1016/j.molmed.2024.03.010. Wu YK, Watson HJ, Del Re AC, et al. Peripheral biomarkers of anorexia nervosa: a meta-analysis. Nutrients. 2024;16(3):e350. doi:10.3390/nu16030350. Brinn A, Stone J. Neutrophil-lymphocyte ratio across psychiatric diagnoses: a cross-sectional study using electronic health records. BMJ Open. 2020;10:e45678. doi:10.1136/bmjopen-2020-045678. Bhikram T, Sandor P. Neutrophil-lymphocyte ratios as inflammatory biomarkers in psychiatric patients. Brain Behav Immun. 2022;105:237–246. doi:10.1016/j.bbi.2022.02.015. Avcil S. Evaluation of the neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and mean platelet volume as inflammatory markers in children with attention-deficit hyperactivity disorder. Psychiatry Clin Neurosci. 2018;72(6):522–530. doi:10.1111/pcn.12679. Binici NC, Güney SA, Neslihan F, Emiroğlu İ. Neutrophil-lymphocyte and platelet-lymphocyte ratios among adolescents with bipolar disorder: a preliminary study. Psychiatry Res. 2018;268:65–71. doi:10.1016/j.psychres.2018.08.065. Bustan Y, Baruch Y, Shoval G, et al. Elevated neutrophil-to-lymphocyte ratio in non-affective psychotic adolescent inpatients: evidence for early association between inflammation and psychosis. Psychiatry Res. 2018;268:102–108. doi:10.1016/j.psychres.2018.02.002. Drapisz A, Golec A, Świerczyńska E, et al. Association between neutrophil-to-lymphocyte ratio and mood polarity in adolescents admitted to an inpatient psychiatric ward. Int Clin Psychopharmacol. 2022;37(4):242–246. doi:10.1097/YIC.0000000000000380. Karatoprak S, Uzun N, Akıncı MA, Dönmez YE. Neutrophil-lymphocyte and platelet-lymphocyte ratios among adolescents with substance use disorder: a preliminary study. Clin Psychopharmacol Neurosci. 2021;19(4):669–676. doi:10.9758/cpn.2021.19.4.669. Önder A, Gizli Çoban Ö, Sürer Adanır A. Elevated neutrophil-to-lymphocyte ratio in children and adolescents with attention-deficit/hyperactivity disorder. Int J Psychiatry Clin Pract. 2021;25(1):43–48. doi:10.1080/13651501.2020.1835965. Önen Ö, Erkuran HÖ, Bağ Ö, Abacıgil F. Blood count parameters as inflammation indicators in children and adolescents diagnosed with depressive disorder. Psychiatry Clin Psychopharmacol. 2021;31(4):425–433. doi:10.5152/pcp.2021.21052. Özyurt G, Binici NC. Increased neutrophil-lymphocyte ratios in depressive adolescents is correlated with the severity of depression. Psychiatry Res. 2018;268:426–431. doi:10.1016/j.psychres.2018.07.033. Özyurt G, Binici NC. The neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in adolescent obsessive-compulsive disorder: does comorbid anxiety disorder affect inflammatory response? Psychiatry Res. 2019;272:311–315. doi:10.1016/j.psychres.2019.01.027. Bou Khalil R, Caldiroli D, Ünver E. Neutrophil-to-lymphocyte ratio variations in relationship with childhood maltreatment in patients with anorexia nervosa: a retrospective cohort study. Eat Weight Disord. 2022;27(7):2201–2212. doi:10.1007/s40519-021-01285-2. Caldiroli A, Galluzzi S, Villa C, et al. Clinical and peripheral biomarkers in female patients affected by anorexia: does the neutrophil/lymphocyte ratio affect severity? Nutrients. 2023;15(3):e456. doi:10.3390/nu15030456. Ünver H, Gökçe Ceylan B, Erdoğdu Yıldırım AB, Perdahlı Fiş N. Serum peripheral markers for inflammation in adolescents with anorexia nervosa. Int J Psychiatry Clin Pract. 2024. doi:10.1080/13651501.2024.2343482. Ikiuo K, Hashimoto R, Murata M. Discussion on the new physical fitness definition in school health program: on the comparison between a new and a previous definition for the physical fitness of school-aged children and the secular trend of the prevalence of obesity and thinness in them from 1980 to 2006. J Child Health. 2010;69(1):6–13. (Article in Japanese). Parker EK, Nagata JM, Austin SB, et al. Higher caloric refeeding is safe in hospitalised adolescent patients with restrictive eating disorders. J Nutr Metab. 2016;2016:e123456. doi:10.1155/2016/123456. Hindley K, Fenton C, McIntosh J. A systematic review of enteral feeding by nasogastric tube in young people with eating disorders. J Eat Disord. 2021;9:34. doi:10.1186/s40337-021-00392-7. Tables Table 1 Clinical characteristics of 55 patients with EDs. variables N (%) Sex Female 50 (90.9) Male 5 (9.1) Diagnosis (AN) AN 47 (85.5) ARFID 8 (14.5) Tube feeding treatment (Yes) Yes 22 (40.0) No 33 (60.0) Race Japanese 55 (100) Mean (SD) Age on admission (months) 154.5 (21.2) Length of hospital stay (days) 104.8 (53.8) %IBW on admission 71.9 (6.2) %IBW at discharge 87.1 (10.0) rate of weight gain (kg/week) 0.489 (0.331) NLR on admission 1.44 (0.68) Table 2. Mixed model for repeated measure. Model 1 Fixed effect Parameters Estimate SE t p-value Intercept 0.380 0.741 0.513 0.608 Tube feeding (No) 0.538 0.190 2.834 0.007 %IBW 0.029 0.008 3.750 <0.001 %IBW 2 -0.001 0.0004 -2.962 0.003 Age (months) 0.006 0.004 1.304 0.198 Gender (Women) 0.457 0.365 1.252 0.216 Diagnosis (AN) -0.040 0.306 -0.130 0.897 Weight gain rate (kg/week) 0.459 0.275 1.666 0.102 Random effect Parameters SD Correlation Intercept 0.510 %IBW 0.026 0.036 Residual 0.797 Model 2 Fixed effect Parameters Estimate SE t p-value Intercept 1.579 0.112 14.042 <0.001 Tube feeding (Yes) 0.434 0.176 2.463 0.017 %IBW 0.023 0.009 2.475 0.014 %IBW 2 -0.0003 0.0005 -0.662 0.508 Tube feeding × %IBW 0.008 0.014 0.557 0.578 Tube feeding × %IBW 2 -0.002 0.001 -2.484 0.013 Random effect Parameters SD Correlation Intercept 0.524 %IBW 0.021 0.352 Residual 0.798 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 19 May, 2025 Read the published version in Journal of Eating Disorders → Version 1 posted Editorial decision: Revision requested 31 Mar, 2025 Reviews received at journal 09 Mar, 2025 Reviewers agreed at journal 26 Feb, 2025 Reviewers invited by journal 16 Feb, 2025 Editor assigned by journal 29 Jan, 2025 Submission checks completed at journal 29 Jan, 2025 First submitted to journal 28 Jan, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5919028","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"correspondence","associatedPublications":[],"authors":[{"id":408673778,"identity":"c6fdd8a1-4e17-4612-b5c2-efe9047fc541","order_by":0,"name":"Yuta 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16:13:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":668240,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5919028/v1/93c61598-94c2-47e6-ad17-fe901948ec31.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Monitoring Neutrophil-to-Lymphocyte Ratio Dynamics for Personalized Treatment in Adolescent Eating Disorders: A retrospective cohort study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEating disorders (EDs), psychiatric conditions manifesting in adolescence, lack established biomarkers for diagnosis or treatment. EDs involve significant disruptions in eating behaviors, leading to medical and psychological complications. Diagnosis is clinically assessed using operational diagnostic criteria, which include weight changes and symptoms, with the Diagnostic and Statistical Manual of Mental Disorders, 5th ed., as an example. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Therapists should also consider ancillary biomarkers such as hormones, neuroimaging, and re-feeding markers [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], though repeating these during treatment is cost-prohibitive. Unlike other psychiatric conditions, EDs are influenced by starvation and malnutrition, complicating the use of biomarkers for other mental health disorders [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Since the heterogeneity of EDs poses challenges in evaluating recovery based on single indicators, such as weight or psychopathological findings, a comprehensive assessment that incorporates multiple related factors could better capture the complexity of recovery. Developing a multimodal predictive model integrating such factors would be clinically valuable for improving personalized treatment and monitoring outcomes in patients with EDs.\u003c/p\u003e \u003cp\u003eRecently, the neutrophil-to-lymphocyte ratio (NLR) has gained attention as a biomarker for psychiatric disorders [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The NLR, derived from routine blood tests, is the ratio of neutrophils to lymphocytes. Neutrophils indicate innate immunity through inflammatory factors, whereas lymphocytes represent adaptive immunity, with low counts indicating compromised health and stress [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Elevated NLR is associated with acute episodes and disease severity in various adolescent psychiatric conditions [\u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11 CR12 CR13\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, in EDs, particularly anorexia nervosa (AN), NLR behaves differently [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Studies have shown that NLR decreases during acute AN, reflecting the body\u0026rsquo;s starvation response [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. As patients recover, the NLR increases, indicating an improved nutritional and inflammatory status. NLR dynamics during ED treatment and their correlation with clinical features remain underexplored.\u003c/p\u003e \u003cp\u003eThis study evaluated NLR trajectories in adolescent ED patients during initial hospitalization to assess their potential as biomarkers. We retrospectively analyzed NLR fluctuations in patients hospitalized for their first ED episode, associating these changes with clinical characteristics to determine NLR's reliability for monitoring disease severity and treatment response.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e A retrospective chart review was conducted with all patients admitted to the psychiatric ward of Jichi Medical University Hospital Tochigi Children's Medical Center between January 1, 2015, and December 31, 2021. The diagnosis was verified by two trained child psychiatrists based on the DSM-5 criteria for AN or avoidant/restrictive feeding and intake disorder (ARFID).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eParticipants and inpatient treatment\u003c/h2\u003e \u003cp\u003eThis study included children with AN or ARFID who received initial inpatient ED treatment. The exclusion criteria were as follows: (i) age over 16 years, (ii) admission weight over 85% of ideal body weight (%IBW), and (iii) inability to measure the NLR at least twice.\u003c/p\u003e \u003cp\u003eInpatient treatment occurred in a closed child psychiatry ward managed by a multidisciplinary team of 3\u0026ndash;4 child psychiatrists, psychologists, nurses, psychiatric social workers, and dieticians. This approach included establishing therapeutic relationships, diagnosis, assessment, psychoeducation, nutritional guidance, food records, re-nutritional therapy using behavioral techniques, and supportive psychotherapy. Psychiatrists met patients at least three times a week to discuss treatment plans, with periodic family interviews to share progress. Nurses provided dietary and lifestyle care and explained the disease stages. The psychologists conducted individual and group therapy sessions. Psychiatric social workers liaised with schoolteachers and offered social support for future school reintegration. Dietitians offered nutritional guidance. Re-nutritional therapy primarily involved oral nutrition with tube feeding if necessary.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eMeasurements\u003c/h3\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSociodemographic and clinical characteristics\u003c/h2\u003e \u003cp\u003eThis study aimed to evaluate NLR dynamics in the inpatient treatment process and its association with sociodemographic and clinical characteristics. We examined the participants\u0026rsquo; sociodemographic and clinical characteristics to identify potential confounding factors: age at admission, sex, classification of eating disorders (AN, ARFID), duration of hospital stay, %IBW on admission, %IBW at discharge, rate of weight gain (kg/week), and gastric tube feeding.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePercentage of ideal body weight (%IBW)\u003c/h3\u003e\n\u003cp\u003e%IBW was calculated via a formula (patient weight \u0026times; 100/standard weight), where the standard weight was determined by the Japan Pediatric Endocrine Society\u0026rsquo;s criteria [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Patients with \u0026lt;\u0026thinsp;85%IBW were defined as having low body weight according to the Hirata method commonly used in Japan to evaluate pediatric physiques.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis examined the correlation between changes in NLR and other variables. NLRs at \u0026ge;\u0026thinsp;38\u0026deg;C were excluded because of potential infectious disease effects. A paired t-test was used to compare %IBW at admission and discharge. Given the expected non-linear relationship between NLR and %IBW influenced by physical and psychological stress during inpatient treatment, a quadratic term for %IBW (%IBW\u0026sup2;) was included in a mixed model for repeated measures analysis. To prevent multicollinearity between %IBW and %IBW\u0026sup2;, %IBW was centered using grand-mean centering. A random slope model was used for %IBW to account for individual variations in its effect on NLR. All analyses were performed with R software (version 4.4.1), and graphs were created using RStudio (2024.04.2\u0026thinsp;+\u0026thinsp;764).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eIn this study, 76 patients were admitted to our hospital for treatment of eating disorders. Among them, two, three, and 16 were excluded because they were older, overweight, and had \u0026lt;2 NLR measurements, respectively. A total of 55 patients were included in the study (Figure 1). The clinical characteristics of the patients are shown in Table 1. A paired t-test revealed that %IBW was significantly higher at discharge than at admission (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.01, data not shown).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2 presents the findings of the mixed model for repeated measures (MMRM) and identifies several predictors of NLR variability. Model 1 was fitted to examine the effects of tube feeding treatment, age in months, %IBW, %IBW\u003csup\u003e2\u003c/sup\u003e, rate of weight gain (kg/week), gender, and diagnosis (AN or ARFID) on the NLR. Fixed effects estimates indicated that tube feeding had a statistically significant effect (β = 0.538, \u003cem\u003ep\u003c/em\u003e = 0.007), with higher NLR values observed in the tube feeding group. The effect of the %IBW was statistically significant (β = 0.029, \u003cem\u003ep\u003c/em\u003e \u0026lt;.\u0026nbsp;0.001). %IBW\u003csup\u003e2\u003c/sup\u003e was also significant (β = -0.001, \u003cem\u003ep\u003c/em\u003e = 0.003), indicating a non-linear relationship between %IBW and NLR, characterized by an upward-convex parabolic trend.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo investigate the interactions between tube feeding and %IBW, variables that were statistically significant in model 1 were included in model 2. No interaction was found between tube feeding and %IBW, but an interaction emerged between tube feeding and %IBW² (β = -0.002, \u003cem\u003ep\u003c/em\u003e = 0.013), indicating that the NLR increased linearly without tube feeding and non-linearly with tube feeding, following an upward-convex parabolic trend. Random effects analysis revealed a standard deviation of 0.524 for random intercepts, which indicated variability in the baseline NLR among individuals. The standard deviation for the random slopes of %IBW\u003csup\u003e2\u003c/sup\u003e was 0.021, which suggests minimal variability in the effect of %IBW on the NLR.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eChanges in NLR in adolescent ED patients during inpatient treatment indicated that body weight recovery was crucial for restoring NLR values. As body weight increased, NLR values progressively normalized, highlighting the importance of physical health in stabilizing inflammatory markers. MMRM analysis showed a linear NLR increase without tube feeding, reflecting gradual recovery with weight gain, and a nonlinear, upward-convex trend with tube feeding, suggesting accelerated weight gain but additional stressors affecting the NLR. The initial NLR values varied significantly among participants; however, the impact of %IBW on NLR was consistent, regardless of the initial NLR values. This indicates that weight restoration is essential for improving NLR values, irrespective of the baseline immune status or social background, as evidenced by the upward NLR trend during treatment.\u003c/p\u003e \u003cp\u003eA previous study reported that NLR tended to decrease during the acute phase of EDs, particularly AN, owing to decreased muscle mass, bone marrow activity, adiponectin levels, and cachexia [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Our findings align with this, as the NLR values at admission were lower in malnourished patients. Importantly, as body weight improved during treatment, the NLR values also showed significant recovery, highlighting the interdependence of nutritional status and immune function. Tube feeding treatment in patients with EDs can elevate NLR, likely owing to both physical and psychological stress. The use of tube feeding in the treatment of EDs has been associated with shorter hospital stays and increased caloric intake, which can facilitate faster weight restoration [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Although generally considered safe, side effects, such as nasal irritation, epistaxis, and anxiety, are common. In some cases, physical restraint may be required; however, our study had no cases that required physical restraint. Additionally, tube feeding treatment may provoke feelings of fear or loss of control due to passive nutritional intake and faster weight restoration [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], potentially contributing to an elevated inflammatory response. Furthermore, the apparent elevation in NLR may have been due to physical irritation and mechanical stimulation associated with tube feeding, rather than reflecting true improvements in the underlying condition, because NLR tended to decrease in the late phase of inpatient treatment with tube feeding. This may reflect the impact of gastric tube removal. Therefore, careful monitoring of changes in NLR after discontinuation of tube feeding is crucial to better understand its true implications and to ensure that NLR dynamics genuinely indicate recovery rather than transient stress responses.\u003c/p\u003e \u003cp\u003eIn this study, we examined NLR as a potential biomarker for evaluating recovery in patients with EDs. However, the complexity and heterogeneity of EDs necessitate a broader approach for recovery assessment [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Future research should incorporate a diverse range of variables, including clinical, biochemical, nutritional, and psychological factors into a unified predictive framework. The integration of these factors would provide a more holistic understanding of recovery dynamics and allow more nuanced assessments tailored to individual patients. Moreover, leveraging advanced methodologies such as machine learning and artificial intelligence could facilitate the development of robust multimodal predictive models. These models would not only improve the accuracy of recovery predictions but also support the implementation of personalized treatment strategies and optimize interventions for specific patient profiles. By addressing the multifaceted nature of EDs, this approach has the potential to significantly enhance the clinical utility and outcomes.\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, as a retrospective analysis, the frequency of NLR measurements decreased during later hospitalization, limiting the assessment of long-term NLR trends. Second, childhood maltreatment, which could influence NLR, was not evaluated. Future studies should assess patients' psychosocial backgrounds to better understand the impact of trauma on NLR fluctuations. Third, differences in tube feeding usage, including duration and methods, and the psychological effects of tube feeding were not considered. Fourth, tube feeding might have triggered hyperactivity in some patients, potentially elevating the neutrophil counts and NLR. This confounder was not assessed and requires further investigation. Future studies should examine the impact of psychosocial factors on immune function and explore the potential influence of tube feeding on inflammatory markers. In this study, the NLR was highlighted as a component of a potential multimodal recovery index. As a quantitative metric, NLR offers valuable insights; however, future studies should aim to incorporate a variety of data types, including other quantitative measures and possibly non-quantitative data, such as imaging. This study advances personalized treatment in EDs by developing a more comprehensive recovery index.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAN\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Anorexia Nervosa\u003c/p\u003e\n\u003cp\u003eARFID\u0026nbsp; \u0026nbsp;Avoidant/restrictive feeding and intake disorder\u003c/p\u003e\n\u003cp\u003eDSM-5\u0026nbsp; \u0026nbsp;Diagnostic and statistical manual of mental disorders. 5th ed.\u003c/p\u003e\n\u003cp\u003eEDs\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Eating disorders\u003c/p\u003e\n\u003cp\u003eICD-10\u0026nbsp; \u0026nbsp;International statistical classification of diseases and related health problems, 10th Revision\u003c/p\u003e\n\u003cp\u003eMMRM\u0026nbsp;Mixed model for repeated measures\u003c/p\u003e\n\u003cp\u003eNLR\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Neutrophil-to-lymphocyte ratio\u003c/p\u003e\n\u003cp\u003e%IBW \u0026nbsp; \u0026nbsp;Percentage of ideal body weight\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study received approval from the Ethics Review Committee of Jichi Medical University. Consent was obtained via an opt-out method, with information provided through documents posted on the websites of the Departments of Psychiatry and Children's Mental Health at Jichi Medical University, ensuring participants were adequately informed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted as a retrospective chart review. Participation was based on an opt-out method, whereby eligible patients and their guardians were informed of the study through documents posted on the website of the Departments of Psychiatry and Children's Mental Health at Jichi Medical University. Individuals who did not wish to participate were given the opportunity to express their decision to opt out. As no personal identifiable information is included in this publication, additional written consent for publication was not required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from Jichi Medical University but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Jichi Medical University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no financial or nonfinancial interests to disclose. Paperpal was used solely for grammar checks to enhance readability, not for text generation. All authors reviewed and edited the manuscript and assume full responsibility for its publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI, Grant Number JP80382951.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eY.I. and T.Y. designed the study. Y.I., K.K. (Kurata), S.O., K.K. (Kurane), R.F., T.M., and H.N. collected the data. Y.M. provided financial support. Y.I., Y.O., T.Y., and S.S. prepared the original draft. Y.O. and T.Y. provided statistical analyses supports. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Editage (www.editage.jp) for English language editing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAmerican Psychiatric Association. \u003cem\u003eDiagnostic and Statistical Manual of Mental Disorders.\u003c/em\u003e 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.\u003c/li\u003e\n\u003cli\u003eHimmerich H, Treasure J. Anorexia nervosa: diagnostic, therapeutic, and risk biomarkers in clinical practice. \u003cem\u003eTrends Mol Med.\u003c/em\u003e 2024;30(4):350\u0026ndash;360. doi:10.1016/j.molmed.2024.03.010.\u003c/li\u003e\n\u003cli\u003eWu YK, Watson HJ, Del Re AC, et al. 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Clinical and peripheral biomarkers in female patients affected by anorexia: does the neutrophil/lymphocyte ratio affect severity? \u003cem\u003eNutrients.\u003c/em\u003e 2023;15(3):e456. doi:10.3390/nu15030456.\u003c/li\u003e\n\u003cli\u003e\u0026Uuml;nver H, G\u0026ouml;k\u0026ccedil;e Ceylan B, Erdoğdu Yıldırım AB, Perdahlı Fiş N. Serum peripheral markers for inflammation in adolescents with anorexia nervosa. \u003cem\u003eInt J Psychiatry Clin Pract.\u003c/em\u003e 2024. doi:10.1080/13651501.2024.2343482.\u003c/li\u003e\n\u003cli\u003eIkiuo K, Hashimoto R, Murata M. Discussion on the new physical fitness definition in school health program: on the comparison between a new and a previous definition for the physical fitness of school-aged children and the secular trend of the prevalence of obesity and thinness in them from 1980 to 2006. \u003cem\u003eJ Child Health.\u003c/em\u003e 2010;69(1):6\u0026ndash;13. (Article in Japanese).\u003c/li\u003e\n\u003cli\u003eParker EK, Nagata JM, Austin SB, et al. Higher caloric refeeding is safe in hospitalised adolescent patients with restrictive eating disorders. \u003cem\u003eJ Nutr Metab.\u003c/em\u003e 2016;2016:e123456. doi:10.1155/2016/123456.\u003c/li\u003e\n\u003cli\u003eHindley K, Fenton C, McIntosh J. A systematic review of enteral feeding by nasogastric tube in young people with eating disorders. \u003cem\u003eJ Eat Disord.\u003c/em\u003e 2021;9:34. doi:10.1186/s40337-021-00392-7.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 Clinical characteristics of 55 patients with EDs.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"321\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003evariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e50 (90.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e5 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eDiagnosis (AN)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eAN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e47 (85.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eARFID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e8 (14.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eTube feeding treatment (Yes)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e22 (40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e33 (60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eRace\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eJapanese\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e55 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eAge on admission (months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e154.5 (21.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eLength of hospital stay (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e104.8 (53.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e%IBW on admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e71.9 (6.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e%IBW at discharge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e87.1 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003erate of weight gain (kg/week)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.489 (0.331)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eNLR on admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e1.44 (0.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTable 2. Mixed model for repeated measure.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 567px;\"\u003e\n \u003cp\u003eModel 1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 567px;\"\u003e\n \u003cp\u003eFixed effect\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eParameters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003eEstimate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003eSE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eIntercept\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.380\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.741\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.513\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.608\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eTube feeding (No)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.538\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.190\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e2.834\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e%IBW\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.029\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e3.750\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e%IBW\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e-0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.0004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e-2.962\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eAge (months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e1.304\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.198\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eGender (Women)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.457\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.365\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e1.252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.216\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eDiagnosis (AN)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e-0.040\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.306\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e-0.130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.897\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eWeight gain rate (kg/week)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.459\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.275\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e1.666\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.102\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 567px;\"\u003e\n \u003cp\u003eRandom effect\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eParameters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003eCorrelation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eIntercept\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.510\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e%IBW\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eResidual\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.797\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 567px;\"\u003e\n \u003cp\u003eModel 2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 567px;\"\u003e\n \u003cp\u003eFixed effect\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eParameters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003eEstimate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003eSE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eIntercept\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e1.579\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.112\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e14.042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eTube feeding (Yes)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.434\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.176\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e2.463\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.017\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e%IBW\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e2.475\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e%IBW\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e-0.0003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.0005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e-0.662\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.508\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eTube feeding \u0026times; %IBW\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.557\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.578\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eTube feeding \u0026times; %IBW\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e-0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e-2.484\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 567px;\"\u003e\n \u003cp\u003eRandom effect\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eParameters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003eCorrelation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eIntercept\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.524\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e%IBW\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.352\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eResidual\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.798\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\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":"journal-of-eating-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joed","sideBox":"Learn more about [Journal of Eating Disorders](http://jeatdisord.biomedcentral.com)","snPcode":"40337","submissionUrl":"https://submission.nature.com/new-submission/40337/3","title":"Journal of Eating Disorders","twitterHandle":"@JEatDisord","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"neutrophil-to-lymphocyte ratio, eating disorders, tube feeding, nutritional status, ideal body weight","lastPublishedDoi":"10.21203/rs.3.rs-5919028/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5919028/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThis study aimed to evaluate the dynamics of the neutrophil-to-lymphocyte ratio (NLR) during the initial hospitalization of patients with eating disorders (EDs) and to assess its potential as a biomarker for monitoring disease severity and treatment response.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective chart review was conducted with 55 patients aged\u0026thinsp;\u0026le;\u0026thinsp;16 years diagnosed with anorexia nervosa or avoidant/restrictive food intake disorder and admitted to Jichi Medical University Hospital between 2015 and 2021. Sociodemographic and clinical characteristics including sex, age, rate of weight gain, percentage of ideal body weight (%IBW), tube feeding treatment, and NLR were obtained. Statistical analyses used a mixed model for repeated measures to assess NLR changes regarding %IBW and other clinical factors.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe NLR at admission was lower in the malnourished state but increased with weight recovery. MMRM revealed that tube feeding treatment and restoration of %IBW significantly predicted an increase in the NLR. The interaction between tube feeding and the quadratic term of %IBW was also significant, indicating distinct patterns of NLR changes: without tube feeding, NLR increased linearly with weight recovery, whereas with tube feeding, NLR exhibited a non-linear, upward-convex parabolic trend.\u003c/p\u003e\u003ch2\u003eDiscussion\u003c/h2\u003e \u003cp\u003eThese findings indicate that NLR may serve as a potential biomarker for monitoring recovery in patients with EDs, reflecting nutritional status and tube feeding-related factors. NLR measurement could be a practical tool for tailoring treatment strategies. Further research is warranted to explore NLR's utility across diverse ED populations and assess its responsiveness to various interventions, advancing personalized medicine in this field.\u003c/p\u003e","manuscriptTitle":"Monitoring Neutrophil-to-Lymphocyte Ratio Dynamics for Personalized Treatment in Adolescent Eating Disorders: A retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-04 09:04:11","doi":"10.21203/rs.3.rs-5919028/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-03-31T15:40:53+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-03-09T13:59:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"143090902181511936094531707531307567892","date":"2025-02-26T07:32:59+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-02-16T15:07:45+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-01-29T14:05:09+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-01-29T09:27:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Eating Disorders","date":"2025-01-28T13:25:34+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-eating-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joed","sideBox":"Learn more about [Journal of Eating Disorders](http://jeatdisord.biomedcentral.com)","snPcode":"40337","submissionUrl":"https://submission.nature.com/new-submission/40337/3","title":"Journal of Eating Disorders","twitterHandle":"@JEatDisord","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"790a2203-569c-41e2-84aa-44fec12e4bef","owner":[],"postedDate":"February 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-05-26T16:09:54+00:00","versionOfRecord":{"articleIdentity":"rs-5919028","link":"https://doi.org/10.1186/s40337-025-01282-2","journal":{"identity":"journal-of-eating-disorders","isVorOnly":false,"title":"Journal of Eating Disorders"},"publishedOn":"2025-05-19 15:58:04","publishedOnDateReadable":"May 19th, 2025"},"versionCreatedAt":"2025-02-04 09:04:11","video":"","vorDoi":"10.1186/s40337-025-01282-2","vorDoiUrl":"https://doi.org/10.1186/s40337-025-01282-2","workflowStages":[]},"version":"v1","identity":"rs-5919028","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5919028","identity":"rs-5919028","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}