RESUMO
Introduction: Hypoxic-ischaemic brain injury (HIBI), is a common sequalae following out-of-hospital cardiac arrest (OOHCA), it is reported as the cause of death in 68% of patients who survive to ICU admission, while other patients can be left with permanent neurological disability. Prediction of neurological outcome follows a multimodal approach, including use of the biomarker, neurone specific enolase (NSE). There is however no definitive cut-off value for poor neurological outcome, and little research has analysed NSE and long-term outcomes in survivors. We investigated an NSE threshold for poor short-term neurological outcome and the relationship between NSE and poor neurological outcome in survivors. Methods: A retrospective study was conducted of all adult OOHCA patients admitted to the Royal County Sussex Hospital ICU between April 2017 and November 2018. NSE levels, Targeted Temperature Management (TTM), cross-sectional imaging, mortality and GCS on ICU discharge were recorded. Assessment of neurological function after a median of 19 months (range 14-32 months) post ICU discharge was undertaken following ICU discharge and related to NSE. Results: NSE levels were measured in 59 patients; of these 36 (61%) had a poor neurological outcome due to hypoxic ischaemic brain injury. Youden's index and ROC analysis established an NSE cut-off value of 64.5 µg/L, with AUC of 0.901, sensitivity of 77.8% and specificity of 100%. Follow-up of 26 survivors after 19 months did not show a significant relationship between NSE after OOHCA and long-term neurological outcome. Conclusion: Our results show that NSE >64.5 µg/L has a poor short-term neurological outcome with 100% specificity. Whilst limited by a low sample size, NSE in survivors showed no relationship with neurological outcome post OOHCA in the long term.
RESUMO
We have previously reported that overexpression of human insulin-like growth factor binding protein (IGFBP)-1 in mice leads to vascular insulin sensitization, increased nitric oxide bioavailability, reduced atherosclerosis, and enhanced vascular repair, and in the setting of obesity improves glucose tolerance. Human studies suggest that low levels of IGFBP-1 are permissive for the development of diabetes and cardiovascular disease. Here we seek to determine whether loss of IGFBP-1 plays a causal role in the predisposition to cardiometabolic disease. Metabolic phenotyping was performed in transgenic mice with homozygous knockout of IGFBP-1. This included glucose, insulin, and insulin-like growth factor I tolerance testing under normal diet and high-fat feeding conditions. Vascular phenotyping was then performed in the same mice using vasomotor aortic ring studies, flow cytometry, vascular wire injury, and angiogenesis assays. These were complemented with vascular phenotyping of IGFBP-1 overexpressing mice. Metabolic phenotype was similar in IGFBP-1 knockout and wild-type mice subjected to obesity. Deletion of IGFBP-1 inhibited endothelial regeneration following injury, suggesting that IGFBP-1 is required for effective vascular repair. Developmental angiogenesis was unaltered by deletion or overexpression of IGFBP-1. Recovery of perfusion following hind limb ischemia was unchanged in mice lacking or overexpressing IGFBP-1; however, overexpression of IGFBP-1 stimulated hindlimb perfusion and angiogenesis in insulin-resistant mice. These findings provide new insights into the role of IGFBP-1 in metabolic and vascular pathophysiology. Irrespective of whether loss of IGFBP-1 plays a causal role in the development of cardiometabolic disorders, increasing IGFBP-1 levels appears effective in promoting neovascularization in response to ischemia.
