PAPE is one of the most dangerous complications following operations, and it is necessary to predict the prognosis of patients early. To the best of our knowledge, this is the first study to investigate predictors and establish a nomogram of 30-day mortality among patients with PAPE following noncardiac surgery. The primary findings of our study were that the NLR was significantly higher in non-surviving patients than in survivors and that plasma albumin was significantly lower in those who died than in survivors; both the NLR and albumin were independent predictors for 30-day mortality among patients with PAPE following noncardiac surgery. Moreover, the nomogram based on the NLR and albumin showed good performance in predicting 30-day mortality in patients with PAPE.
In our research, 101 patients were included, and 24 patients died within 30 days, corresponding to a 30-day mortality rate of 23.8%. According to previous studies, the mortality rate of APE patients ranges from 8.1%-25.3%[12, 18-20]. Our results showed that the mortality of our cohort was within this range. In our research, the NLR was identified as an effective prognostic biomarker for PAPE patients. The NLR is the comprehensive presentation of systemic inflammation and the balance between neutrophils and lymphocytes in CBCs. Previous studies have shown that an elevated NLR is associated with an increased rate of hospital mortality among patients with acute pulmonary embolism[13], acute exacerbation of chronic obstructive pulmonary disease[21], and acute type A aortic dissection[22]; of 30-day mortality among patients with acute pulmonary embolism[19], acute kidney injury[23], ST-elevation myocardial infarction[24], and intracerebral hemorrhage[25, 26]; and of long-term mortality among patients with ST-elevation myocardial infarction[27], breast cancer[28] and epithelial ovarian cancer[29].
The link between inflammation and pulmonary embolism has been well investigated, although the underlying mechanism is not completely understood. The relationship between them may be linked by cytokines, proinflammatory cytokines, and acute-phase proteins, such as CRP, IL-8, and tumor necrosis factor, which promote the procoagulant state and play an important role in the progression of venous thromboembolism by inducing the expression of tissue factors. In addition, it has recently been reported that inflammatory mediators, such as polyphosphates and bradykinin, can directly activate contact systems and initiate external coagulation pathways[30-32]. In our research, we found that the NLR was an independent predictor of 30-day mortality in patients with PAPE, and the area under the curve of the NLR was 0.823. Therefore, we concluded that the NLR is a simple and effective prognostic predictor for patients with PAPE.
We also found that albumin was significantly lower in those who died than in survivors. To our knowledge, this is the first study to indicate the relationship between albumin and mortality in patients with PAPE. Albumin is an indicator of the nutritional status of patients and can regulate the anticoagulation system to some extent. Hypoproteinemia has been confirmed to be associated with mortality in patients with acute pulmonary embolism in previous studies[16]. In a previous study, the mechanism of the association between albumin and mortality was partly explained. Plasma albumin can interact with NO to some extent and generate S-nitrosoproteins, which then promote vasomotor activity and inhibit platelet aggregation. When albumin levels drop, the effect will be weakened[33, 34]. In addition, plasma albumin has important antioxidant, anti-inflammatory and drug carrier effects in human physiological functions[35]. Therefore, a lower plasma albumin concentration will inevitably lead to a decrease or loss of these effects.
There were also some limitations in our research. First, as a single-center study, only 101 patients met the criteria and were included in our study, which was a small sample size. The small sample size makes it impossible to classify and discuss patients with PAPE for specific operations, such as arthroplasty and gastrointestinal cancer resection. Second, although the nomogram showed good performance in terms of the AUC, calibration curve and DCA, independent validation is needed. Finally, as a retrospective study, our research had its own limitations, and some potential predictors were not included in our research. We hope that multicenter and prospective research can be performed to confirm our conclusion in the future.