The gastrointestinal tract is an important digestive, endocrine and immune organ in the human body and is also the largest bacterial reservoir in the human body [7]. AGI secondary to pDOC, in addition to affecting the absorption and utilization of nutrients, will also lead to the translocation of toxins in the intestinal flora due to the destruction of the gastrointestinal mucosal barrier, aggravate the systemic immune inflammatory response, and eventually lead to septic shock and multiorgan failure [8]. Therefore, it is particularly important to predict the AGI of pDOC patients and intervene early. However, there is still a lack of clinical tools for the early prediction of secondary AGI in pDOC patients.
After exclusion according to the exclusion criteria, a total of 165 patients were included, and the results showed that AGI occurred in up to 55.15% of patients. According to previous research [9,10,11] and our clinical experience, this study selected 35 risk factors, covering many aspects, such as the degree of organ damage and treatment factors, in patients with chronic disorder of consciousness. Logistic regression analysis confirmed that CRS-R score, DAO, PCT, ALB, and I-FABP were risk factors for AGI in patients with pDOC.
The Brain Injury-Interdisciplinary Special Interest Group, Disorders of Consciousness Task Force [12] completed an evidence-based retrospective study of the behavioral scale for patients with consciousness disorders in 2010, and believed that the CRS-R was the most acceptable of all scales. The CRS-R is currently considered to be effective for assessing pDOC [13,14,15]. Therefore, in this study, CRS-R was used to evaluate the state of consciousness of patients.Research suggests that there is a bidirectional neuromodulation pathway between the brain and the gut, that is, the brain-gut axis (BGA). It is mediated by immune factors [16, 17]. When the brain is damaged by irreversible ischemia and hypoxia, the function of the cerebral cortex decreases, resulting in a decline in the ability of the central nervous system to regulate the enteric nervous system, and the function of the enteric nervous system is relatively independent. This increased sensitivity is more likely to cause gastrointestinal dysfunction. This study found that there is a significant correlation between the CRS-R score and AGI at admission, and multivariate logistic regression analysis showed that CRS-R score is one of the independent predictors of AGI in pDOC patients. Gastrointestinal dysfunction is likely to occur in these patients.
I-FABP is a group of low-molecular-weight proteins that are highly specifically distributed in mature small intestinal mucosal epithelial cells. Under normal circumstances, serum I-FABP levels are very low, but in early intestinal ischemia, epithelial cells are damaged. When the permeability increases (≤ 2 h), I-FABP can be released into the blood through the cell membrane surface and has high stability, so it is suitable as a marker of early damage to intestinal mucosal cells [18]. As an oxidase in the cytoplasm of villous epithelial cells, DAO is highly active. Its activity is closely related to the nucleic acid and protein synthesis of mucosal cells. It can reflect the integrity and repair ability of intestinal epithelial cells and is sensitive to the assessment of early intestinal mucosal damage [19]. Therefore, the increase in blood I-FABP and DAO levels is closely related to the occurrence of AGI. This study concluded that for every 1 μg/L increase in I-FABP, the possibility of AGI in patients with chronic disorder of consciousness increased by 0.223, and for every 1 mmol/L increase in DAO, the possibility of AGI in pDOC patients increased by 3.561 times, which deserves early clinical attention.
PCT is the calcitonin polypeptide precursor produced by thyroid C cells. Under pathological conditions, such as trauma, bacterial infection, and cardiogenic shock, organs and tissues other than the thyroid are stimulated to produce PCT in the blood, which can be detected within 2 h. It has high sensitivity and specificity and is a commonly used clinical indicator of inflammation. Patients with chronic disorder of consciousness often have low immune function. Once AGI occurs, intestinal ischemia and hypoxia, endotoxin release, and intestinal bacterial translocation lead to infection, all of which can lead to an increase in PCT. A study [20] showed that with the increase in AGI grade, the level of PCT increased significantly, and AGI may be a precipitating and stimulating factor of SIRS and MODS. This study found that there is a significant correlation between PCT and AGI, and multivariate logistic regression analysis showed that PCT is one of the independent predictors of AGI in patients with pDOC. For every 1 ng/mL increase in PCT, the possibility of AGI increases by 5.144 times.
Serum ALB levels are a common indicator reflecting the nutritional status of the body, and ALB helps to maintain intravascular osmotic pressure, promotes the transport of substances, and scavenges free radicals. ALB is reduced in acute inflammation, and hypoalbuminemia is associated with systemic inflammatory responses [11]. A systematic review of 4190 critically ill patients [21] found that reduced serum ALB levels were associated with all-cause mortality. Plasma colloid osmotic pressure decreases due to hypoalbuminemia, resulting in edema of tissues and organs. When mucosal edema occurs in the gastrointestinal tract, it easily causes acute gastrointestinal dysfunction.
Previous studies [22] have shown that logistic regression models fitting multiple indicators to establish a prediction model can significantly improve the predictive ability of the target outcome. Risk factors were used to establish a joint prediction model to predict the occurrence probability of AGI in pDOC patients. The ROC curve analysis showed that the AUC of the joint prediction model was 0.931, which was higher than the AUC of any single independent influencing factor, with a sensitivity of 83.5% and a specificity of 93.2%, which proved that the joint prediction model had high predictive value and was superior to any single predictor. The data were subjected to the H–L test, all P > 0.05, and a calibration curve was drawn based on the test results, indicating that the prediction model had good goodness-of-fit and good prediction stability.
In conclusion, the occurrence of AGI in pDOC patients involves many aspects, such as intestinal ischemia and hypoxia, immune response imbalance, and mucosal barrier damage, which is the result of the combined effect of multiple factors. The AGI prediction model for pDOC patients established in this study can be used in the clinic and helps to predict the occurrence of AGI in pDOC patients. For patients with potential risk of AGI, relevant intervention measures should be taken early, such as early enteral nutrition, post-pyloric feeding, and avoiding the use of drugs that impair gastrointestinal function.Nevertheless, this study also has certain limitations. First, as a single-center retrospective study, the sample size of this study was relatively small, and the results of the study may be affected by potential confounding factors and selection bias. Further research with multicenter and large samples is needed. For age-stratified studies, the predictive power of the prediction model in pDOC patients of different ages remains to be further validated.