Changes in Adipose Tissue Structure and Function in the Context of Sepsis
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Difference in adipocyte cytokine secretion between patients with sepsis, and patients without sepsis, and between SAT and VAT samples
研究概览
简要总结
Obesity has been shown to increase adverse outcomes in some critically ill patients e.g. those with COVID-19. For patients with sepsis this association is less clear cut but there is evidence that body fat distribution, resulting from impaired subcutaneous adipose tissue function, is associated with adverse clinical outcomes in critical care. The investigators aim to study subcutaneous adipose tissue function in lean and obese sepsis patients in critical care and compare that to healthy controls.
First, the study will investigate differences in adipose tissue function (inflammation and mitochondrial function) related to obesity. Second, the investigators will examine whether lean critically ill patients with sepsis have enhanced adipose tissue inflammation and mitochondrial dysfunction compared to lean controls and whether this is further exacerbated by obesity.
Patients will be either undergoing emergency abdominal surgery, or will have been admitted to a critical care unit with a diagnosis of sepsis.
The investigators will collect blood and adipose tissue biopsies from the patients, and these will be analysed for markers of inflammation and of mitochondrial function.
The aim is to better understand the relationship between obesity, inflammation, mitochondrial dysfunction and sepsis. The investigators hope that this may improve the understanding of the pathophysiology of sepsis and allow more targeted interventions for patients based on differences in their baseline metabolic state.
详细描述
Hypothesis The hypothesis is that adipose tissue from patients who are critically ill with sepsis will show changes in structure, increased inflammatory function, and increased mitochondrial dysfunction in comparison to control patients without sepsis. The investigators also hypothesise that that increased inflammatory function will be more pronounced in VAT than in SAT.
Aims The investigators aim to investigate potential differences in adipose tissue structure, inflammatory function, and mitochondrial dysfunction between individuals with and without sepsis, and between SAT and VAT.
Study design
There will be two patient cohorts:
- Patients undergoing emergency surgery with a diagnosis of sepsis
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For patients in a critical care unit:
- •Diagnosis of sepsis by the criteria set out in the Sepsis-3 guidelines:
- •Suspected diagnosis of infection
- •Acute change in Sequential Organ Failure Assessment (SOFA) of ≥2
- •For patients undergoing an operation:
- •Undergoing emergency abdominal surgery
- •Diagnosis of sepsis by the criteria set out in the Sepsis-3 guidelines:
- •Suspected diagnosis of infection
- •Acute change in Sequential Organ Failure Assessment (SOFA) of ≥2
排除标准
- •Patient moribund and death is perceived to be imminent
- •≥48 hours from diagnosis with sepsis
- •Pregnancy
- •Prisoners
- •Receiving treatment-dose anticoagulant medication
- •Declined consent
结局指标
主要结局
Difference in adipocyte cytokine secretion between patients with sepsis, and patients without sepsis, and between SAT and VAT samples
时间窗: Within 72 hours of admission to ICU
Cytokine quantitation from adipose tissue samples will be carried out using using magnetic bead multiple arrays or by commercial ELISA to investigate for any possible differences between patients with and without sepsis, and between SAT and VAT samples
次要结局
- Differences in adipocyte pro-inflammatory gene expression(Within 72 hours of admission to ICU)
- Differences in SVF cytokine secretion(Within 72 hours of admission to ICU)
- Differences in adipocyte size(Within 72 hours of admission to ICU)
- Differences in capacity of pre-adipocytes to differentiate into mature adipocytes(Within 72 hours of admission to ICU)
- Differences in mitochondrial morphology(Within 72 hours of admission to ICU)
- Differences in adipocyte mitochondrial number(Within 72 hours of admission to ICU)
- Differences in adipocyte mitochondrial viability(Within 72 hours of admission to ICU)