Akshata Pandiri, (2022) Single Centre, Prospective Observational study to Evaluate Association Between Circulating Citrullinated Histone H3 and Sepsis Induced Complications in Paediatric Patients with Clinical Sepsis. Masters thesis, Christian Medical College, Vellore.
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Abstract
INTRODUCTION: It has been postulated that sepsis triggers citrullination of histone H3(CitH3) and leads to Neutrophil extracellular trap formation and release of CitH3 into circulation. This can induce Disseminated intravascular coagulation (DIC), subsequent organ failure and death. Many studies in adult population and murine studies have substantiated and proposed, CitH3 as a diagnostic and prognostic marker in sepsis. AIM OF THE STUDY: To evaluate whether CitH3 can be used as a prognostic indicator in paediatric patients with clinical sepsis OBJECTIVES: 1. To compare CitH3 levels between sepsis patients and non-sepsis controls. 2. To evaluate whether CitH3 levels in clinical sepsis have an impact on survival in children with clinical sepsis. 3. To compare the CitH3 levels in patients with and without disseminated intravascular coagulation (DIC), number of organ failures. METHODS: Paediatric patients with clinical sepsis were recruited along with preoperative children as controls. Clinical and lab data were collected and analysed. Complications associated with sepsis if any, were identified. Using a sandwich ELISA technique, levels of CitH3 in plasma of cases and controls were measured. The relationship between CitH3 levels and mortality, DIC, organ failure was analysed. RESULTS: CitH3 levels [Median(minimum-maximum)] were significantly higher in 90 children with clinical sepsis [ 1.275ng/ml (0.01-23.10)] when compared to 38 controls [0.35ng/ml (0.15-0.94); p<0.0002)]. The area under curve (95% CI) for distinguishing sepsis from non-sepsis patients using CitH3 was 0.70 (0.61-0.80). The median Cit H3 values with Scrub typhus infection (2.480ng/ml (0.53-8.62)) and Paediatric Inflammatory Multisystem Syndrome-Temporally associated with SARSCoV-2 (1.36ng/ml (0.16-19.6)) were significantly higher than those with controls (0.35ng/ml (0.15-0.94) and other gram-negative infections (0.24ng/ml (0.14-2.50) (p 0.0042). There was no significant difference between circulating histone H3 levels in survivors and non-survivors, patients with and without DIC or number of organ failures (p>0.05). In the logistic regression analysis, fibrinogen <242 mg/dL [odds ratio (OR) 12.388; 95% confidence interval (CI) 1.335-114.980; p = 0.027] and INR >1.43 (OR 15.740; 95% CI 1.236–200.426; p= 0.034), within the first 24 h of admission were independently associated with mortality of sepsis. However, other variables including total count, lactate, APTT and DIC score were not significant predictors of sepsis mortality. CONCLUSION: 1. Citrullinated histone H3 levels measured at admission within 24 hours were higher in children with clinical sepsis than controls. 2. Paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-PIMS-TS currently known as Multisystem inflammatory syndrome of children (MIS-C) is associated with raised circulating citrullinated Histone H3 levels when compared to controls. This suggests a role of NETosis in the pathophysiology of this novel entity. 3. Citrullinated histone H3 levels were highest in scrub typhus, followed by PIMSTS. The levels in scrub typhus were significantly higher than controls and other gram-negative infections. 4. Circulating histone levels were not associated with coagulopathy, Multi-Organ Dysfunction and do not predict mortality therefore cannot be used as a prognostication marker in paediatric sepsis patients. 5. Baseline raised INR > 1.43 and low fibrinogen levels < 242mg/dl in paediatric clinical sepsis patients were independent predictors of mortality in a multivariate analysis.
| Item Type: | Thesis (Masters) |
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| Additional Information: | 201931051 |
| Uncontrolled Keywords: | Single Centre, Prospective Observational study, Evaluate Association, Circulating Citrullinated Histone H3, Sepsis Induced Complications, Paediatric Patients, Clinical Sepsis. |
| Subjects: | MEDICAL > Immunohaematology Blood Transfusion > MEDICAL > Immunohaematology Blood Transfusion |
| Depositing User: | Subramani R |
| Date Deposited: | 27 Jun 2021 01:48 |
| Last Modified: | 03 Mar 2024 06:06 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/17821 |
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