RESUMO
BACKGROUND: Acute appendicitis (AA) is the most common emergency general surgical condition worldwide. Diagnosis is challenging and incorporates clinical, biochemical and radiological investigations. Our aim was to provide data from routine practice investigating widely utilised diagnostic methods from a single centre within the United Kingdom. METHODS: We conducted a retrospective observational cohort study of patients who underwent a laparoscopic appendicectomy for AA between April 2022 and March 2023. AA was defined as the presence of transmural polymorphonuclear leukocytes in histology. Subgroup analysis was performed on paediatric patients. Factors associated with AA were investigated, and the diagnostic utility of biochemical and radiological investigations was examined. RESULTS: A total of 330 appendicectomies were analysed. We found an overall negative appendicectomy rate (NAR) of 38% and 48% in paediatric patients. Independent factors associated with AA on the multivariate analysis included elevated neutrophil counts (>7 × 109/L) (OR 4.04), elevated CRP (>5 mg/L) (OR 3.04) and a radiological diagnosis (OR 8.0). Computerised tomography (CT) and ultrasound had sensitivity/specificity of 98%/47% and 35%/86%, respectively. The positive-predictive values were 85% for CT and 50% for ultrasound, and the negative-predictive values were 86% for CT and 77% for ultrasound. CONCLUSION: Our study has highlighted the importance of utilising a combination of factors to improve the diagnostic certainty of AA. However, our routine practice data have shown different sensitivities and specificities of imaging in comparison to existing literature, resulting in a high NAR. Further real-world data are needed to understand whether these differences from the existing data are seen in other clinical settings.
RESUMO
BACKGROUND: Obesity drives maladaptive changes in the white adipose tissue (WAT) which can progressively cause insulin resistance, type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated liver disease (MASLD). Obesity-mediated loss of WAT homeostasis can trigger liver steatosis through dysregulated lipid pathways such as those related to polyunsaturated fatty acid (PUFA)-derived oxylipins. However, the exact relationship between oxylipins and metabolic syndrome remains elusive and cross-tissue dynamics of oxylipins are ill-defined. METHODS: We quantified PUFA-related oxylipin species in the omental WAT, liver biopsies and plasma of 88 patients undergoing bariatric surgery (female N = 79) and 9 patients (female N = 4) undergoing upper gastrointestinal surgery, using UPLC-MS/MS. We integrated oxylipin abundance with WAT phenotypes (adipogenesis, adipocyte hypertrophy, macrophage infiltration, type I and VI collagen remodelling) and the severity of MASLD (steatosis, inflammation, fibrosis) quantified in each biopsy. The integrative analysis was subjected to (i) adjustment for known risk factors and, (ii) control for potential drug-effects through UPLC-MS/MS analysis of metformin-treated fat explants ex vivo. FINDINGS: We reveal a generalized down-regulation of cytochrome P450 (CYP)-derived diols during obesity conserved between the WAT and plasma. Notably, epoxide:diol ratio, indicative of soluble epoxide hydrolyse (sEH) activity, increases with WAT inflammation/fibrosis, hepatic steatosis and T2DM. Increased 12,13-EpOME:DiHOME in WAT and liver is a marker of worsening metabolic syndrome in patients with obesity. INTERPRETATION: These findings suggest a dampened sEH activity and a possible role of fatty acid diols during metabolic syndrome in major metabolic organs such as WAT and liver. They also have implications in view of the clinical trials based on sEH inhibition for metabolic syndrome. FUNDING: Wellcome Trust (PS3431_WMIH); Duke-NUS (Intramural Goh Cardiovascular Research Award (Duke-NUS-GCR/2022/0020); National Medical Research Council (OFLCG22may-0011); National Institute of Environmental Health Sciences (Z01 ES025034); NIHR Imperial Biomedical Research Centre.