{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T12:30:19Z","timestamp":1787056219008,"version":"build-2736575974"},"reference-count":21,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"unspecified","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["IIRPSG-2024-01-02334"],"award-info":[{"award-number":["IIRPSG-2024-01-02334"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,8,6]]},"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Paediatric sepsis remains a formidable challenge in global child health, contributing significantly to morbidity and mortality, especially in resource-constrained settings. Accurate early prognostication of disease trajectory is imperative for effective triage and timely intervention; however, existing biomarkers and clinical scoring systems are often limited by insufficient specificity, operational complexity or limited applicability across diverse clinical settings. One potential avenue for improving early prognostication is investigating novel biomarkers. Cereblon (CRBN), a multifunctional protein implicated in immune modulation, has shown variable associations with outcomes in adult sepsis, while its role in paediatric sepsis remains unexplored. This study aims to assess the potential of CRBN expression as an early prognostic biomarker in paediatric sepsis, thereby informing clinical decision-making and improving patient outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This prospective observational paediatric intensive care unit (PICU)-based study will enrol 240 children aged 2 months to 15 years with sepsis using a consecutive non-probability sampling method. Pediatric Sequential Organ Failure Assessment (pSOFA) scores will be recorded at admission and at 24 hours. Blood samples will be collected at admission to assess CRBN mRNA expression by quantitative real-time PCR and protein levels by ELISA. The primary outcome will be the correlation of CRBN with 28-day mortality. Secondary outcomes will assess its correlation with the pSOFA score, C-reactive protein, duration of mechanical ventilation and duration of PICU stay. CRBN levels will be compared between survivors and non-survivors, and correlations with pSOFA score, inflammatory markers and clinical outcomes will be assessed using Pearson\u2019s or Spearman\u2019s tests as appropriate. Prognostic performance will be assessed using Receiver operating characteristics (ROC) curve and area under curve (AUC) value with Youden-derived cut-offs. Multivariable regression will be performed to adjust for key confounders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval was obtained from the Institutional Ethics Committee, All India Institute of Medical Sciences, Raebareli, prior to study initiation (IEC Code-2024-4-EMP-EXP-9). Written informed consent will be obtained from parents or guardians. The study findings will be disseminated through peer-reviewed publications and scientific conferences. The reporting of study results will adhere to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines to ensure transparency and completeness.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2026-121640","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T11:50:20Z","timestamp":1787053820000},"page":"e121640","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Development of Cereblon (CRBN) as an early prognostic biomarker in Paediatric Sepsis: a Prospective Observational Study Protocol"],"prefix":"10.1136","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8133-013X","authenticated-orcid":false,"given":"Namita","family":"Mishra","sequence":"first","affiliation":[{"name":"Pediatrics, All India Institute of Medical Sciences Raebareli, Raebareli, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0503-2322","authenticated-orcid":false,"given":"Ankit","family":"Gupta","sequence":"additional","affiliation":[{"name":"Biochemistry, All India Institute of Medical Sciences Raebareli, Raebareli, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasna","family":"Gupta","sequence":"additional","affiliation":[{"name":"Pediatrics, All India Institute of Medical Sciences Raebareli, Raebareli, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mritunjay","family":"Kumar","sequence":"additional","affiliation":[{"name":"Pediatrics, All India Institute of Medical Sciences Raebareli, Raebareli, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Shukla","sequence":"additional","affiliation":[{"name":"Pediatrics, All India Institute of Medical Sciences Raebareli, Raebareli, Uttar Pradesh, India"},{"name":"Pediatrics, T.S. Mishra Medical College, Lucknow, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"2026081804501299000_16.8.e121640.1","doi-asserted-by":"crossref","DOI":"10.3389\/fped.2022.829119","article-title":"Pediatric Sepsis Research: Where Are We and Where Are We Going?","volume":"10","author":"Massaud-Ribeiro","year":"2022","journal-title":"Front Pediatr"},{"key":"2026081804501299000_16.8.e121640.2","doi-asserted-by":"crossref","DOI":"10.1186\/s13054-018-2052-7","article-title":"Mortality and morbidity in community-acquired sepsis in European pediatric intensive care units: a prospective cohort study from the European Childhood Life-threatening Infectious Disease Study (EUCLIDS)","volume":"22","author":"Boeddha","year":"2018","journal-title":"Crit Care"},{"key":"2026081804501299000_16.8.e121640.3","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"The Lancet"},{"key":"2026081804501299000_16.8.e121640.4","article-title":"Pediatric emergency triage systems","volume":"41","author":"Simon Junior","year":"2022","journal-title":"Rev paul pediatr"},{"key":"2026081804501299000_16.8.e121640.5","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2021-052565","article-title":"The Current and Future State of Pediatric Sepsis Definitions: An International Survey","volume":"149","author":"Morin","year":"2022","journal-title":"Pediatrics"},{"key":"2026081804501299000_16.8.e121640.6","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2023-325984"},{"key":"2026081804501299000_16.8.e121640.7","doi-asserted-by":"crossref","DOI":"10.3390\/biom14010097","article-title":"Biomarkers for Serious Bacterial Infections in Febrile Children","volume":"14","author":"Bernardi","year":"2024","journal-title":"Biomolecules"},{"key":"2026081804501299000_16.8.e121640.8","article-title":"The Various Scoring Systems in Pediatric Intensive Care Units: A Prospective Observational Study","volume":"15","author":"Jyotsna","year":"2023","journal-title":"Cureus"},{"key":"2026081804501299000_16.8.e121640.9","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/9130608","article-title":"Cereblon: A Protein Crucial to the Multiple Functions of Immunomodulatory Drugs as well as Cell Metabolism and Disease Generation","volume":"2017","author":"Shi","year":"2017","journal-title":"J Immunol Res"},{"key":"2026081804501299000_16.8.e121640.10","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.bbrc.2017.11.098","article-title":"Cereblon deficiency confers resistance against polymicrobial sepsis by the activation of AMP activated protein kinase and heme-oxygenase-1","volume":"495","author":"Gil","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"2026081804501299000_16.8.e121640.11","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2016.226","article-title":"Cereblon negatively regulates TLR4 signaling through the attenuation of ubiquitination of TRAF6","volume":"7","author":"Min","year":"2016","journal-title":"Cell Death Dis"},{"key":"2026081804501299000_16.8.e121640.12","doi-asserted-by":"crossref","first-page":"5215","DOI":"10.2147\/IJGM.S428505","article-title":"The Relationship Between the Expression of CRBN in Peripheral Blood and the Severity and Prognosis of Adult Sepsis","volume":"16","author":"Kuang","year":"2023","journal-title":"Int J Gen Med"},{"key":"2026081804501299000_16.8.e121640.13","first-page":"6081","article-title":"Incidence of cereblon protein in intensive care patients: a cross-sectional study","volume":"27","author":"Ayvat","year":"2023","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"2026081804501299000_16.8.e121640.14","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.0179"},{"key":"2026081804501299000_16.8.e121640.15","doi-asserted-by":"crossref","unstructured":"Abdallah EAA , Mansour HH , El-Shabrawi M , et al . The prevalence, characteristics, and outcome of severe sepsis at three pediatric intensive care units in a limited-resource setting: a prospective cohort study. 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