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Title: The diagnostic role of complement cascade biomarkers in acute appendicitis in adults presenting with right iliac fossa pain
Author: Marshall, Morwena J.
ISNI:       0000 0004 7231 7664
Awarding Body: Exeter and Plymouth Peninsula Medical School
Current Institution: Exeter and Plymouth Peninsula Medical School
Date of Award: 2017
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Acute appendicitis (AA) is the most common cause for emergency abdominal surgery in the Western world. Diagnostic error results in unnecessary operations in up to thirty per cent of patients with associated morbidity and economic cost. Conventional biomarkers of inflammation, white cell count (WCC) and C-reactive protein (CRP), aid diagnosis but are slow and non-specific. We hypothesised that the complement (C) cascade would be more rapidly triggered by acute inflammation of the appendix, allowing for discrimination between AA and other conditions (non-AA). Aim The aim of this thesis was to: “explore the potential role of the C cascade in the diagnosis ofAA in adults presenting with right iliac fossa (RIF) pain”. Methods A prospective pilot observational study recruited adults with right iliac fossa (RIF) pain admitted to hospital with a clinical suspicion of AA. Admission and serial plasma C4, C3, iC3b and TCC assays and admission urine C3a ELISA results were compared with reference standards for AA to assess diagnostic performance by receiver operating characteristic (ROC) curves. The effect of biomarker interpretation on diagnostic accuracy was studied through varying thresholds of test positivity derived from population, study cohort and individualised patient trend data. The time dependent nature of biomarkers was explored through the effect of duration of symptoms and trend analysis. Results Seventy-four adults were recruited to the study, 26 (35%) were male with a median age of 33 years (range 18 to 84). Twenty-two (30%) patients were diagnosed with AA. Isolated admission C proteins did not discriminate between AA and non-AA. Admission WCC and CRP performed well but their diagnostic performance was enhanced when added to clinical characteristics in the Alvarado score (ROC area under curve (AUC) 0.85 (95% Cl 0.76-0.94). The Alvarado score performed exceptionally in females of reproductive age, with a ROC AUC of 0.92 (95% Cl 0.82-1.00). Trend analysis of TCC over four hours produced the most accurate C cascade biomarker in our study with a ROC AUC of 0.84 (0.69-0.99). Urine C3a was detected in fourteen patients (27%) with RIF pain. Conclusion Our study corroborates the diagnostic role of the Alvarado score in AA in adults with RIF pain and suggests new candidates from the C cascade for further validation. A proposed care pathway incorporating the Alvarado score, CRP and TCC A4 is presented for further evaluation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available