Evaluation of Ketone Bodies in Blood during Vomiting Episodes for Diagnosing Cyclic Vomiting Syndrome: A Nested Case-Control Study

Evaluation of Ketone Bodies in Blood during Vomiting Episodes for Diagnosing Cyclic Vomiting Syndrome: A Nested Case-Control 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 Short Report Evaluation of Ketone Bodies in Blood during Vomiting Episodes for Diagnosing Cyclic Vomiting Syndrome: A Nested Case-Control Study Yuya Saito, Yukiko Osawa, Toshimasa Obonai This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4290471/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Cyclic vomiting syndrome (CVS) is a very common emergency pediatric condition but can be challenging to diagnose due to the need to ascertain a history of recurrent vomiting episodes. The present study aimed to evaluate the utility of the blood ketone (beta-hydroxybutyric acid) level in diagnosing CVS by investigating ketone bodies in pediatric patients presenting to the emergency department with vomiting symptoms. The study included 395 patients who underwent rapid beta-hydroxybutyric acid testing for vomiting episodes between August 24, 2021 and September 30, 2023. Of these, 21 (5.3%) were diagnosed with CVS while 374 (94.7%) were classified as non-CVS. Additionally, 21 patients with CVS were compared with 63 controls matched for age and fasting duration. The beta-hydroxybutyric acid level was higher (3.6 mmol/L vs. 1.7 mmol/L, P < 0.001) in the CVS group than in the control subjects. The diagnostic probability model for CVS based on age (≥ 8 years) and beta-hydroxybutyric acid level (≥ 2.9 mmol/L) in the present study demonstrated a specificity of 97.1%, sensitivity of 42.9%, and positive likelihood ratio of 14.3. Conclusion : The blood ketone level was higher in pediatric patients with CVS presenting to the emergency department with vomiting symptoms than in matched control subjects. Age and the blood ketone level may have the potential to aid the early diagnosis of cyclic vomiting syndrome. Cyclic Vomiting Syndrome fasting duration blood ketone level hypoglycemia Figures Figure 1 What is known？ ・Infants and young children have lower glycogen stores in muscles and the liver than adults, making them more susceptible to an increase in blood ketone during fasting. ・Children with cyclic vomiting syndrome had higher fatty acid oxidation and ketogenesis than their healthy counterparts on an epinephrine challenge test. What is new ？ ・During vomiting episodes, children with cyclic vomiting syndrome had a higher ketone body level than those who did not have the syndrome despite being older. INTRODUCTION Cyclic vomiting syndrome (CVS), one of the most common emergency pediatric conditions, may require the administration of IV fluids and hospitalization. CVS affects approximately 2% of children aged 5 to 10 years, with the average age at onset being 5.2 years. The frequency of vomiting episodes can decrease the patient’s quality of life, for example by increasing school absences [ 1 ]. Triggers for the vomiting episodes include infection (41%), psychological stress (34%), dietary factors (26%), and menstruation (13%). Although the International Headache Society Classification [ 2 ] and the Rome IV criteria for functional gastrointestinal disorders [ 3 ] include diagnostic criteria for CVS, the multiple visits to the emergency department sometimes required for a definitive diagnosis may cause a delay in treatment [ 4 ]. Various etiologies have been proposed for CVS, including abnormalities of mitochondrial energy production, disorders of fatty acid oxidation, endocrine abnormalities, autonomic nervous system dysfunction, gastrointestinal motility disorders, migraines, and psychosomatic conditions. However, the exact cause remains unclear [ 5 ]. One study investigating the pathophysiology of CVS found that children with this condition had higher fatty acid oxidation and ketogenesis than their healthy counterparts on an epinephrine challenge test [ 6 ]. However, whether the blood ketone level is actually elevated in pediatric patients with CVS during vomiting episodes has not been determined. The present study aimed to investigate the ketone (beta-hydroxybutyrate acid) level in the blood of patients with CVS during vomiting episodes to assess their potential contribution to diagnosing this disease. PATIENTS AND METHODS Study Design Patients with vomiting symptoms visiting the pediatric emergency department at Tama-Hokubu Medical Center have their blood beta-hydroxybutyrate acid level measured using Control Freestyle Precision Neo (Abbott Japan Co., Ltd.). The observation items include sex, age, weight, time from symptom onset to visit, last sugar intake, past vomiting episodes, medical history, treatment details, and hospitalization status. In the present study, all these items were obtained from the patients’ medical records. This study was performed in line with the principles of the Declaration of Helsinki. Opt-out consent was conducted from August 24, 2021 to January 30, 2024 after the study was approved by the Tama-Hokubu Medical Center Ethics Committee (number 3–12). Information about the clinical study was posted on the institutional website, and the subjects were provided an opportunity to prohibit the use of their personal data. The present study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines. CVS was defined by the following criteria: (1) recurrent, intense nausea and vomiting lasting several hours to several days and occurring at least twice every six months; (2) typical vomiting episodes; (3) intervals between episodes of several weeks to several months and good health during periods of asymptomaticity; and (4) other diseases unexplainable by an appropriate evaluation. Participation The inclusion criteria were 1) age ≤ 15 years at the time of consultation, 2) difficulty with oral intake due to vomiting, and 3) history of rapid beta-hydroxybutyrate acid testing. The exclusion criteria were 1) the presence of a metabolic or endocrine disorder and (2) the presence of sepsis or seizures. Outcome The primary outcome was the blood beta-hydroxybutyrate acid level during a vomiting episode. The secondary outcomes were the identification of CVS risk factors and the creation of a diagnostic model for CVS. Statistical analysis The data were analyzed from January 1 through February 29, 2024. The beta-hydroxybutyrate acid and glucose levels in patients with CVS and control subjects matched by age and fasting duration were evaluated using the Mann-Whitney test. The effects of the risk factors of CVS, including blood beta-hydroxybutyrate acid level, blood glucose level, age, body weight, and fasting duration, were estimated using univariate and multivariate logistic regression models. Two-sided p < .05 was considered to indicate statistical significance. All the data were analyzed using Stata version 16 (StataCorp LP, College Station, TX). RESULTS Study Population and blood beta-hydroxybutyrate acid levels The study included 402 patients with vomiting and rapid beta-hydroxybutyrate acid testing conducted between August 24, 2021 and September 30, 2023. Among these, seven patients were excluded, including those with an underlying condition, such as adrenal insufficiency, diabetes mellitus or abnormal ketone body metabolism as well as cases with repeated testing. Of the 395 patients analyzed, there were 21 patients (5.3%) with CVS and 374 patients (94.7%) with non-cyclic vomiting syndrome (non-CVS). Additionally, the 21 patients with CVS were compared with up to three population-based control groups matched by age and fasting duration. Age, sex, weight, fasting duration, time from onset, blood beta-hydroxybutyrate acid level, blood glucose level, history of intravenous drip, and hospitalization status were compared between the CVS and non-CVS groups (Table 1). CVS tended to occur in older individuals with a higher body weight who had a higher beta-hydroxybutyric acid level, lower blood glucose level, and a higher frequency of intravenous drip administration and hospitalization. No significant difference was observed in terms of sex, fasting duration or time after the onset of vomiting. Although a comparison of the CVS group with the matched control subjects failed to reveal any differences in characteristics, the former still had a higher beta-hydroxybutyric acid level (3.6 mmol/L vs. 1.7 mmol/L, P < .001) and lower blood glucose level (73.0 mg/dL vs. 104.5 mg/dL, P < .001) (Fig. 1 ). Factors predicting a diagnosis of CVS Univariate analysis found that of the categories of age ≥ 8 years, body weight ≥ 22 kg, fasting duration ≥ 14 hours, blood beta-hydroxybutyrate acid level ≥ 2.9 mmol/L, and blood glucose ≤ 80mg/dL, all but fasting duration were significantly associated with CVS. Moreover, multivariate analysis found Fthat age (odds ratio: 8.13; 95% confidence interval: 1.84 to 36.0; P = .006) and blood beta-hydroxybutyrate acid level (odds ratio: 6.06; 95% confidence interval: 1.62 to 22.8; P = .008) were significantly associated with CVS. When the patients were aged 8 years or older and the blood beta-hydroxybutyrate acid level was 2.9 mmol/L or higher, the specificity for diagnosing CVS was 97.1%, the sensitivity was 42.9%, and the positive likelihood ratio was 14.5. DISCUSSION The present study found that patients with CVS had a higher blood ketone level than subjects with no CVS. Although CVS cannot be diagnosed solely on the basis of the blood ketone level, it may be diagnosable if age is also considered. Ketone bodies are produced through the beta-oxidation of lipids when glucose is deficient in the body during fasting to provide an alternative energy source [ 7 ]. Due to the depleted glycogen stores in the muscles and liver, young individuals tend to have a higher ketone level while fasting [ 8 ]. In the present study, the older patients with CVS had a lower glucose level along with a higher ketone level. Presumably, younger individuals ware able to maintain the essential energy requirement during acute, illness-associated fasting unlike during a controlled fasting test. Why the ketone level should be higher in patients with CVS than in control subjects matched for age and fasting duration is unclear, but apart from mechanisms such as fatty acid oxidation enhancement under stress-induced epinephrine, it is possible that these patients had poor oral intake from symptom onset to fasting. Fluid replacement and antiemetic medications are effective for managing vomiting episodes in patients with CVS [ 9 ]. Oral rehydration therapy is the first choice for frequent acute gastroenteritis, but CVS, delaying presentation to the emergency department for more than 24 hours or delaying treatment may increase the risk of hospitalization [ 10 ]. Early diagnosis is essential for properly managing patients with CVS during vomiting episodes and for avoiding hospitalization. The diagnostic probability model for CVS based on age and blood ketone level proposed in the present study demonstrated a specificity of 97.1%, suggesting that CVS can be recognized early when the patient is older than 8 years and the blood beta-hydroxybutyrate acid level ≥ 2.9 mmol/L during vomiting episodes. The present study has several limitations. First, the amount of oral intake from symptom onset to fasting was not investigated. Second, underlying conditions in the non-CVS group which may have caused vomiting and poor oral intake were not considered. Last, some of the items in the differential diagnosis of CVS may not have been excluded. The differential diagnosis of CVS is crucial, and although the CVS group in the present study may have had an underlying disease, no significant abnormalities were found in the patients for whom hormonal tests, organic acid analysis, amino acid analysis, and abdominal imaging studies were performed. CONCLUSION CVS is characterized by a high blood ketone level during episodes of vomiting, and age and the blood ketone level may be used to diagnose this condition at an early stage. Abbreviations CVS : Cyclic Vomiting Syndrome non-CVS : non-Cyclic Vomiting Syndrome Declarations Acknowledgement: We thank James Robert Valera for his assistance with editing this manuscript, Megumi Wada and Yuki Kojima for their assistance with collecting the data, and all the clinicians and hospital staff for their dedication to operating the pediatric emergency service daily. Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing interests: The authors have no relevant financial or non-financial interests to disclose. Author Contributions Drafting of the article: Yuya Saito Conception, data collection, and design: Yuya Saito Critical revision: Yukiko Osawa and Toshimasa Obonai Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Tama-Hokubu Medical Center (August 24, 2021/No. 3-12). Consent to participate: Information about the clinical study was posted on the institutional website, and the subjects were provided an opportunity to prohibit the use of their personal data. Data availability: The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request. References Li BUK, Balint JP (2000) Cyclic vomiting syndrome: evolution in our understanding of a brain-gut disorder. Adv Pediatr 47:117–160 Headache Classification Committee of the International Headache Society (IHS) (2013) The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 33:629–808. https://doi.org/10.1177/0333102413485658 Hymas JS, Di Lorenzo C, Saps M, Shulman RJ, Staiano A, van Tilburg M (2016) Functional Disorders: Children and Adolescents. Gastroenterology 150:1456–1468. https://doi.org/10.1053/j.gastro.2016.02.015 Venkatesan T, Tarbell S, Adams K, McKanry J, Barribeau T, Beckmann K, Hogan WJ, Kumar N, Li BUK (2010) A survey of emergency department use in patients with cyclic vomiting syndrome. BCM Emerg Med 10:4. https://doi.org/10.1186/1471-227X-10-4 Li BU, Murray RD, Heitlinger LA, Robbins JL, Hayes JR (1998) Heterogeneity of diagnoses presenting as cyclic vomiting. Pediatrics 102:583–587. https://doi.org/10.1542/peds.102.3.583 Kenshi F, Kihou M, Katsuko S, Chizuko N (1974) Shoni ki ni okeru beta jyuyoutai hannousei kousinn jyoutai [Hyperactive states of beta-receptor reactivity in childhood]. Nihon Rinsho 32:115–126 Ghosh A, Banerjee I, Morris AAM (2016) Recognition, assessment and management of hypoglycaemia in childhood. Arch Dis Child 101:575–580. https://doi.org/10.1136/archdischild-2015-308337 Bonnefont JP, Specola NB, Vassault A, Lombes A, Ogier H, de Klerk JBC et al (1990) The fasting test in paediatrics: application to the diagnosis of pathological hypo-and hyperketotic states. Eur J Pediatr 9:80–85. https://doi.org/10.1007/BF02072043 Gui S, Patel N, Issenman R, Kam AJ (2019) Acute Management of Pediatric Cyclic Vomiting Syndrome: A Systematic Review. J Pediatr 214:158–164e4. https://doi.org/10.1016/j.jpeds.2019.06.057 Abdulkader ZM, Bali N, Vaz K, Yacob D, Di Lorenzo C, Lu PL (2021) Predictors of Hospital Admission for Pediatric Cyclic Vomiting Syndrome. J Pediatr 232:154–158. https://doi.org/10.1016/j.jpeds.2020.11.055 Tables Table 1. Patient Characteristics Characteristics Total, n (%) CVS, n (%) non-CVS, n (%) n = 395 (100%) n = 21 (5.3%) n = 374 (94.7%) p value Age, years 5.1 ± 3.5 8.6 ± 3.2 4.9 ± 3.4 < 0.001 a Sex, n (%) Male 243 (64.5) 11 (52.4) 232 (62.0) Female 152 (35.5) 10 (47.6) 142 (38.0) 0.782 b Body weight, kg 17.9 ± 9.7 24.3 ± 8.3 17.5 ± 9.7 < 0.001 a Fasting duration, hours 10.6 ± 9.7 11.4 ± 7.4 10.5 ± 9.9 0.324 a Time after the start of vomiting, hours 36.8 ± 39.3 27.0 ± 25.2 37.3 ± 39.9 0.877 a Beta-hydroxybutyric acid, mmol/L 2.4 ± 2.0 3.6 ± 1.8 2.3 ± 2.0 0.002 a Glucose, mg/dL 93.7 ± 25.3 73.0 ± 18.5 94.8 ± 25.2 < 0.001 a Intravenous infusion, n (%) 244 (56.7) 20 (95.2) 228 (61.0) 0.001 b hospitalization, n (%) 174 (44.1) 15 (71.4) 159 (42.5) 0.009 b Abbreviations: CVS, cyclic vomiting syndrome; non-CVS, non-cyclic vomiting syndrome Plus–minus values indicate the mean ± SD. a Mann-Whitney test b Chi-square test Additional Declarations No competing interests reported. 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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-4290471","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":299199511,"identity":"4c2a908f-7a77-4428-9b5c-bb940507dc5c","order_by":0,"name":"Yuya Saito","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8ElEQVRIiWNgGAWjYFACxsYHHwwkmNnkDx8A8iRkiNDC3Gw4o8KGnU+CLQGkhYcILext0jxn0vjlJHgMQFzCWgzOH2yTnNl2WJpNuufzqxs1FjwM7IePbsCr5UZis8XHtsPGbDJnt1nnHAM6jCct7QZ+LYyNN4G2JLMx5G4zzmEDapHgMcOv5fzBBmnetsP1bQw5z4xz/hGj5UBiE8j7zGwSOcyPc9uI0CIJ9AsokJnZeI6ZMef2SfCwEfIL3/njD8FRKd/e/Phzzrc6OX72w8fwalE4gGCzSYBJfMpBQL4BwWb+QEj1KBgFo2AUjEwAAG6ES29nMd5IAAAAAElFTkSuQmCC","orcid":"","institution":"Tama-Hokubu Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Yuya","middleName":"","lastName":"Saito","suffix":""},{"id":299199512,"identity":"f147142e-f639-4857-9f8f-13def1b25712","order_by":1,"name":"Yukiko Osawa","email":"","orcid":"","institution":"Tama-Hokubu Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Yukiko","middleName":"","lastName":"Osawa","suffix":""},{"id":299199513,"identity":"f58686f5-dbfb-46b2-be08-394ad775fd96","order_by":2,"name":"Toshimasa Obonai","email":"","orcid":"","institution":"Tama-Hokubu Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Toshimasa","middleName":"","lastName":"Obonai","suffix":""}],"badges":[],"createdAt":"2024-04-19 02:59:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4290471/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4290471/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":56140161,"identity":"d3a5edaf-cc3e-4e82-a11d-f0e09b45816c","added_by":"auto","created_at":"2024-05-09 04:06:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":20674,"visible":true,"origin":"","legend":"\u003cp\u003eBlood Ketone and Glucose Levels in the CVS Group and Matched Controls\u003c/p\u003e\n\u003cp\u003eAbbreviations: CVS, cyclic vomiting syndrome\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4290471/v1/52793ca6469c8211e1be8ba0.png"},{"id":56477187,"identity":"395030c8-56df-477c-9c48-2de690528eb7","added_by":"auto","created_at":"2024-05-14 17:46:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":361179,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4290471/v1/b23f284d-1984-4503-bfbb-042e4a4208ef.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluation of Ketone Bodies in Blood during Vomiting Episodes for Diagnosing Cyclic Vomiting Syndrome: A Nested Case-Control Study","fulltext":[{"header":"What is known？","content":"\u003cp\u003e・Infants and young children have lower glycogen stores in muscles and the liver than adults, making them more susceptible to an increase in blood ketone during fasting.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e・Children with cyclic vomiting syndrome had higher fatty acid oxidation and ketogenesis than their healthy counterparts on an epinephrine challenge test.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is new\u003c/strong\u003e\u003cstrong\u003e？\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e・During vomiting episodes, children with cyclic vomiting syndrome had a higher ketone body level than those who did not have the syndrome despite being older.\u003c/p\u003e"},{"header":"INTRODUCTION","content":"\u003cp\u003eCyclic vomiting syndrome (CVS), one of the most common emergency pediatric conditions, may require the administration of IV fluids and hospitalization. CVS affects approximately 2% of children aged 5 to 10 years, with the average age at onset being 5.2 years. The frequency of vomiting episodes can decrease the patient\u0026rsquo;s quality of life, for example by increasing school absences [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Triggers for the vomiting episodes include infection (41%), psychological stress (34%), dietary factors (26%), and menstruation (13%). Although the International Headache Society Classification [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] and the Rome IV criteria for functional gastrointestinal disorders [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] include diagnostic criteria for CVS, the multiple visits to the emergency department sometimes required for a definitive diagnosis may cause a delay in treatment [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eVarious etiologies have been proposed for CVS, including abnormalities of mitochondrial energy production, disorders of fatty acid oxidation, endocrine abnormalities, autonomic nervous system dysfunction, gastrointestinal motility disorders, migraines, and psychosomatic conditions. However, the exact cause remains unclear [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. One study investigating the pathophysiology of CVS found that children with this condition had higher fatty acid oxidation and ketogenesis than their healthy counterparts on an epinephrine challenge test [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, whether the blood ketone level is actually elevated in pediatric patients with CVS during vomiting episodes has not been determined. The present study aimed to investigate the ketone (beta-hydroxybutyrate acid) level in the blood of patients with CVS during vomiting episodes to assess their potential contribution to diagnosing this disease.\u003c/p\u003e"},{"header":"PATIENTS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003ePatients with vomiting symptoms visiting the pediatric emergency department at Tama-Hokubu Medical Center have their blood beta-hydroxybutyrate acid level measured using Control Freestyle Precision Neo (Abbott Japan Co., Ltd.). The observation items include sex, age, weight, time from symptom onset to visit, last sugar intake, past vomiting episodes, medical history, treatment details, and hospitalization status. In the present study, all these items were obtained from the patients\u0026rsquo; medical records. This study was performed in line with the principles of the Declaration of Helsinki. Opt-out consent was conducted from August 24, 2021 to January 30, 2024 after the study was approved by the Tama-Hokubu Medical Center Ethics Committee (number 3\u0026ndash;12). Information about the clinical study was posted on the institutional website, and the subjects were provided an opportunity to prohibit the use of their personal data. The present study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines.\u003c/p\u003e \u003cp\u003eCVS was defined by the following criteria: (1) recurrent, intense nausea and vomiting lasting several hours to several days and occurring at least twice every six months; (2) typical vomiting episodes; (3) intervals between episodes of several weeks to several months and good health during periods of asymptomaticity; and (4) other diseases unexplainable by an appropriate evaluation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eParticipation\u003c/h2\u003e \u003cp\u003eThe inclusion criteria were 1) age\u0026thinsp;\u0026le;\u0026thinsp;15 years at the time of consultation, 2) difficulty with oral intake due to vomiting, and 3) history of rapid beta-hydroxybutyrate acid testing. The exclusion criteria were 1) the presence of a metabolic or endocrine disorder and (2) the presence of sepsis or seizures.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eOutcome\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was the blood beta-hydroxybutyrate acid level during a vomiting episode. The secondary outcomes were the identification of CVS risk factors and the creation of a diagnostic model for CVS.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe data were analyzed from January 1 through February 29, 2024. The beta-hydroxybutyrate acid and glucose levels in patients with CVS and control subjects matched by age and fasting duration were evaluated using the Mann-Whitney test. The effects of the risk factors of CVS, including blood beta-hydroxybutyrate acid level, blood glucose level, age, body weight, and fasting duration, were estimated using univariate and multivariate logistic regression models. Two-sided p\u0026thinsp;\u0026lt;\u0026thinsp;.05 was considered to indicate statistical significance. All the data were analyzed using Stata version 16 (StataCorp LP, College Station, TX).\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population and blood beta-hydroxybutyrate acid levels\u003c/h2\u003e \u003cp\u003eThe study included 402 patients with vomiting and rapid beta-hydroxybutyrate acid testing conducted between August 24, 2021 and September 30, 2023. Among these, seven patients were excluded, including those with an underlying condition, such as adrenal insufficiency, diabetes mellitus or abnormal ketone body metabolism as well as cases with repeated testing. Of the 395 patients analyzed, there were 21 patients (5.3%) with CVS and 374 patients (94.7%) with non-cyclic vomiting syndrome (non-CVS). Additionally, the 21 patients with CVS were compared with up to three population-based control groups matched by age and fasting duration. Age, sex, weight, fasting duration, time from onset, blood beta-hydroxybutyrate acid level, blood glucose level, history of intravenous drip, and hospitalization status were compared between the CVS and non-CVS groups (Table\u0026nbsp;1). CVS tended to occur in older individuals with a higher body weight who had a higher beta-hydroxybutyric acid level, lower blood glucose level, and a higher frequency of intravenous drip administration and hospitalization. No significant difference was observed in terms of sex, fasting duration or time after the onset of vomiting. Although a comparison of the CVS group with the matched control subjects failed to reveal any differences in characteristics, the former still had a higher beta-hydroxybutyric acid level (3.6 mmol/L vs. 1.7 mmol/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.001) and lower blood glucose level (73.0 mg/dL vs. 104.5 mg/dL, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eFactors predicting a diagnosis of CVS\u003c/h2\u003e \u003cp\u003eUnivariate analysis found that of the categories of age\u0026thinsp;\u0026ge;\u0026thinsp;8 years, body weight\u0026thinsp;\u0026ge;\u0026thinsp;22 kg, fasting duration\u0026thinsp;\u0026ge;\u0026thinsp;14 hours, blood beta-hydroxybutyrate acid level\u0026thinsp;\u0026ge;\u0026thinsp;2.9 mmol/L, and blood glucose\u0026thinsp;\u0026le;\u0026thinsp;80mg/dL, all but fasting duration were significantly associated with CVS. Moreover, multivariate analysis found Fthat age (odds ratio: 8.13; 95% confidence interval: 1.84 to 36.0; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.006) and blood beta-hydroxybutyrate acid level (odds ratio: 6.06; 95% confidence interval: 1.62 to 22.8; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.008) were significantly associated with CVS. When the patients were aged 8 years or older and the blood beta-hydroxybutyrate acid level was 2.9 mmol/L or higher, the specificity for diagnosing CVS was 97.1%, the sensitivity was 42.9%, and the positive likelihood ratio was 14.5.\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe present study found that patients with CVS had a higher blood ketone level than subjects with no CVS. Although CVS cannot be diagnosed solely on the basis of the blood ketone level, it may be diagnosable if age is also considered.\u003c/p\u003e \u003cp\u003eKetone bodies are produced through the beta-oxidation of lipids when glucose is deficient in the body during fasting to provide an alternative energy source [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Due to the depleted glycogen stores in the muscles and liver, young individuals tend to have a higher ketone level while fasting [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In the present study, the older patients with CVS had a lower glucose level along with a higher ketone level. Presumably, younger individuals ware able to maintain the essential energy requirement during acute, illness-associated fasting unlike during a controlled fasting test. Why the ketone level should be higher in patients with CVS than in control subjects matched for age and fasting duration is unclear, but apart from mechanisms such as fatty acid oxidation enhancement under stress-induced epinephrine, it is possible that these patients had poor oral intake from symptom onset to fasting.\u003c/p\u003e \u003cp\u003eFluid replacement and antiemetic medications are effective for managing vomiting episodes in patients with CVS [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Oral rehydration therapy is the first choice for frequent acute gastroenteritis, but CVS, delaying presentation to the emergency department for more than 24 hours or delaying treatment may increase the risk of hospitalization [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Early diagnosis is essential for properly managing patients with CVS during vomiting episodes and for avoiding hospitalization. The diagnostic probability model for CVS based on age and blood ketone level proposed in the present study demonstrated a specificity of 97.1%, suggesting that CVS can be recognized early when the patient is older than 8 years and the blood beta-hydroxybutyrate acid level\u0026thinsp;\u0026ge;\u0026thinsp;2.9 mmol/L during vomiting episodes.\u003c/p\u003e \u003cp\u003eThe present study has several limitations. First, the amount of oral intake from symptom onset to fasting was not investigated. Second, underlying conditions in the non-CVS group which may have caused vomiting and poor oral intake were not considered. Last, some of the items in the differential diagnosis of CVS may not have been excluded. The differential diagnosis of CVS is crucial, and although the CVS group in the present study may have had an underlying disease, no significant abnormalities were found in the patients for whom hormonal tests, organic acid analysis, amino acid analysis, and abdominal imaging studies were performed.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eCVS is characterized by a high blood ketone level during episodes of vomiting, and age and the blood ketone level may be used to diagnose this condition at an early stage.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCVS : Cyclic Vomiting Syndrome\u003c/p\u003e\n\u003cp\u003enon-CVS : non-Cyclic Vomiting Syndrome\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank James Robert Valera for his assistance with editing this manuscript, Megumi Wada and Yuki Kojima for their assistance with collecting the data, and all the clinicians and hospital staff for their dedication to operating the pediatric emergency service daily.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDrafting of the article: Yuya Saito\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConception,\u0026nbsp;data\u0026nbsp;collection, and design: Yuya Saito\u0026nbsp; \u003c/p\u003e\n\u003cp\u003eCritical revision:\u0026nbsp;Yukiko Osawa\u0026nbsp;and\u0026nbsp;Toshimasa Obonai\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of\u0026nbsp;Tama-Hokubu Medical Center\u0026nbsp;(August 24, 2021/No. 3-12).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformation about the clinical study was posted on the institutional website, and the subjects were provided an opportunity to prohibit the use of their personal data. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLi BUK, Balint JP (2000) Cyclic vomiting syndrome: evolution in our understanding of a brain-gut disorder. Adv Pediatr 47:117\u0026ndash;160\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeadache Classification Committee of the International Headache Society (IHS) (2013) The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 33:629\u0026ndash;808. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1177/0333102413485658\u003c/span\u003e\u003cspan address=\"10.1177/0333102413485658\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHymas JS, Di Lorenzo C, Saps M, Shulman RJ, Staiano A, van Tilburg M (2016) Functional Disorders: Children and Adolescents. Gastroenterology 150:1456\u0026ndash;1468. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1053/j.gastro.2016.02.015\u003c/span\u003e\u003cspan address=\"10.1053/j.gastro.2016.02.015\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVenkatesan T, Tarbell S, Adams K, McKanry J, Barribeau T, Beckmann K, Hogan WJ, Kumar N, Li BUK (2010) A survey of emergency department use in patients with cyclic vomiting syndrome. BCM Emerg Med 10:4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/1471-227X-10-4\u003c/span\u003e\u003cspan address=\"10.1186/1471-227X-10-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi BU, Murray RD, Heitlinger LA, Robbins JL, Hayes JR (1998) Heterogeneity of diagnoses presenting as cyclic vomiting. Pediatrics 102:583\u0026ndash;587. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1542/peds.102.3.583\u003c/span\u003e\u003cspan address=\"10.1542/peds.102.3.583\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKenshi F, Kihou M, Katsuko S, Chizuko N (1974) \u003cem\u003eShoni ki ni okeru beta jyuyoutai hannousei kousinn jyoutai\u003c/em\u003e [Hyperactive states of beta-receptor reactivity in childhood]. Nihon Rinsho 32:115\u0026ndash;126\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGhosh A, Banerjee I, Morris AAM (2016) Recognition, assessment and management of hypoglycaemia in childhood. Arch Dis Child 101:575\u0026ndash;580. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1136/archdischild-2015-308337\u003c/span\u003e\u003cspan address=\"10.1136/archdischild-2015-308337\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBonnefont JP, Specola NB, Vassault A, Lombes A, Ogier H, de Klerk JBC et al (1990) The fasting test in paediatrics: application to the diagnosis of pathological hypo-and hyperketotic states. Eur J Pediatr 9:80\u0026ndash;85. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/BF02072043\u003c/span\u003e\u003cspan address=\"10.1007/BF02072043\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGui S, Patel N, Issenman R, Kam AJ (2019) Acute Management of Pediatric Cyclic Vomiting Syndrome: A Systematic Review. J Pediatr 214:158\u0026ndash;164e4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jpeds.2019.06.057\u003c/span\u003e\u003cspan address=\"10.1016/j.jpeds.2019.06.057\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbdulkader ZM, Bali N, Vaz K, Yacob D, Di Lorenzo C, Lu PL (2021) Predictors of Hospital Admission for Pediatric Cyclic Vomiting Syndrome. J Pediatr 232:154\u0026ndash;158. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jpeds.2020.11.055\u003c/span\u003e\u003cspan address=\"10.1016/j.jpeds.2020.11.055\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Patient Characteristics\u003c/div\u003e\n \u003ctable id=\"Tabb\" border=\"1\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eCharacteristics\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eTotal, n (%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eCVS, n (%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003enon-CVS, n (%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003en\u0026thinsp;=\u0026thinsp;395 (100%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003en\u0026thinsp;=\u0026thinsp;21 (5.3%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003en\u0026thinsp;=\u0026thinsp;374 (94.7%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003ep\u003c/span\u003e value\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAge, years\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e5.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e8.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eSex, n (%)\u003c/div\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 \u003cdiv class=\"SimplePara\"\u003eMale\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e243 (64.5)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e11 (52.4)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e232 (62.0)\u003c/div\u003e\n \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 \u003cdiv class=\"SimplePara\"\u003eFemale\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e152 (35.5)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e10 (47.6)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e142 (38.0)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.782\u003csup\u003eb\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eBody weight, kg\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e17.9\u0026thinsp;\u0026plusmn;\u0026thinsp;9.7\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e24.3\u0026thinsp;\u0026plusmn;\u0026thinsp;8.3\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e17.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.7\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eFasting duration, hours\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e10.6\u0026thinsp;\u0026plusmn;\u0026thinsp;9.7\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e11.4\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e10.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.9\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.324\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eTime after the start of vomiting, hours\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e36.8\u0026thinsp;\u0026plusmn;\u0026thinsp;39.3\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e27.0\u0026thinsp;\u0026plusmn;\u0026thinsp;25.2\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e37.3\u0026thinsp;\u0026plusmn;\u0026thinsp;39.9\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.877\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eBeta-hydroxybutyric acid, mmol/L\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.002\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eGlucose, mg/dL\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e93.7\u0026thinsp;\u0026plusmn;\u0026thinsp;25.3\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e73.0\u0026thinsp;\u0026plusmn;\u0026thinsp;18.5\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e94.8\u0026thinsp;\u0026plusmn;\u0026thinsp;25.2\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eIntravenous infusion, n (%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e244 (56.7)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e20 (95.2)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e228 (61.0)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.001\u003csup\u003eb\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003ehospitalization, n (%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e174 (44.1)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e15 (71.4)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e159 (42.5)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.009\u003csup\u003eb\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAbbreviations: CVS, cyclic vomiting syndrome; non-CVS, non-cyclic vomiting syndrome\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cdiv class=\"SimplePara\"\u003ePlus\u0026ndash;minus values indicate the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003csup\u003ea\u003c/sup\u003eMann-Whitney test\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003csup\u003eb\u003c/sup\u003eChi-square test\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Cyclic Vomiting Syndrome, fasting duration, blood ketone level, hypoglycemia","lastPublishedDoi":"10.21203/rs.3.rs-4290471/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4290471/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCyclic vomiting syndrome (CVS) is a very common emergency pediatric condition but can be challenging to diagnose due to the need to ascertain a history of recurrent vomiting episodes. The present study aimed to evaluate the utility of the blood ketone (beta-hydroxybutyric acid) level in diagnosing CVS by investigating ketone bodies in pediatric patients presenting to the emergency department with vomiting symptoms. The study included 395 patients who underwent rapid beta-hydroxybutyric acid testing for vomiting episodes between August 24, 2021 and September 30, 2023. Of these, 21 (5.3%) were diagnosed with CVS while 374 (94.7%) were classified as non-CVS. Additionally, 21 patients with CVS were compared with 63 controls matched for age and fasting duration. The beta-hydroxybutyric acid level was higher (3.6 mmol/L vs. 1.7 mmol/L, P \u0026lt; 0.001) in the CVS group than in the control subjects. The diagnostic probability model for CVS based on age (≥ 8 years) and beta-hydroxybutyric acid level (≥ 2.9 mmol/L) in the present study demonstrated a specificity of 97.1%, sensitivity of 42.9%, and positive likelihood ratio of 14.3.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: The blood ketone level was higher in pediatric patients with CVS presenting to the emergency department with vomiting symptoms than in matched control subjects. Age and the blood ketone level may have the potential to aid the early diagnosis of cyclic vomiting syndrome.\u003c/p\u003e","manuscriptTitle":"Evaluation of Ketone Bodies in Blood during Vomiting Episodes for Diagnosing Cyclic Vomiting Syndrome: A Nested Case-Control Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-09 02:25:51","doi":"10.21203/rs.3.rs-4290471/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"044672ec-c601-4206-9f2c-a5e7f0e11424","owner":[],"postedDate":"May 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-14T17:46:41+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-09 02:25:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4290471","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4290471","identity":"rs-4290471","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}