1 Factor associated with the development of vascular crisis
1.1 Haemoglobin
Haemoglobin is a standard objective clinical indicator to determine whether a patient is anaemic, and haemoglobin levels <130 g/L in men and <120 g/L in women are considered anaemic. Some studies have found that patients with perioperative anaemia are at an increased risk of flap graft failure in flap grafting, with a 0.5-fold decrease in flap failure for every 1g/dL increase in perioperative haemoglobin concentration.[6, 7]. This is consistent with the findings of the present study, which showed that higher haemoglobin levels are a protective factor against the development of vascular complications. Haixuan Wu et al. [8] showed that low haemoglobin leads to an increased chance of complications after flap grafting. Therefore, they recommended a moderate increase in haemoglobin levels to maintain postoperative haemoglobin levels above ten g/dL to promote the early recovery of patients after flap grafting[8, 9].However, there are no specific guidelines for perioperative blood transfusion in patients with grafts. Other studies have suggested that perioperative blood transfusions may increase the risk of postoperative infections [10].
1.2 Fibrinogen
Fibrinogen has been considered essential for platelet coagulation, and studies have shown that blood in a hypercoagulable state increases the risk of thrombosis in patients after free flap grafting[11]. The results of this study showed that patients with high preoperative fibrin levels were at increased risk of vascular crisis, with a 1.7-fold increase in the risk of flap vascular crisis for every 1 g/dL increase in patient fibrin concentration, suggesting that elevated fibrinogen concentrations can lead to increased blood viscosity, induce the development of atherosclerosis, and cause a slowing of blood circulation, increasing the risk of thrombosis[12]. This is consistent with the view of Yang Lianghui et al. that high fibrinogen puts the blood in a hypercoagulable state and makes it more susceptible to thrombosis leading to the development of a crisis[13].
1.3 Smoking
Smoking is an independent risk factor for the development of vascular crises. This study shows that vascular crisis occurs 4.43 times more frequently in smoke patients than in non-smokers. Smoking disrupts normal vascular physiology, causes vasospasm, and decreases blood flow to the surgical incision site[14, 15]. Furthermore, nicotine in tobacco irritates the blood vessels, causing vasoconstriction, which reduces the blood supply to the recipient area, and does not provide adequate oxygen and nutrients to the skin flap after transplantation. Therefore, patients should be advised to quit smoking before surgery and be smoke-free in the ward [16].
1.4 Operation time
This study shows that prolonged operative time leads to an increased risk of vascular crisis after flap grafting and that the increased operative time may be the result of a combination of factors, including but not limited to the complexity of the procedure, the limited surgical experience of the surgeon[17]. Ishimaru et al. [18] conducted a study reviewing national databases in Japan, where they analysed 2846 patients and found that longer operative times were associated with free flap failure. Additionally, Sanati-Mehrizy et al.[17] a 2015 study of 2013 patients found an association between flap failure and operative time by univariate analysis.
1.5 Peripheral vascular disease
Peripheral vascular disease refers mainly to atherosclerotic stenosis or occlusive lesions of the lower extremity arteries that cause chronic or acute ischemic symptoms in the lower extremity, including asymptomatic atherosclerotic disease of the lower extremity, intermittent claudication, severe limb ischemia, and acute limb ischemia[19]. Ishimaru et al. a study of head and neck flap grafting showed that patients with peripheral vascular disease were more likely to develop flap failure after flap grafting, consistent with the results of the present study[18]. Peripheral vascular disease is mainly due to advanced age, diabetes mellitus, and hypertension, and other studies[20] showed that diabetes mellitus is an independent risk factor for the vascular crisis, and it may be that diabetes mellitus causes microvascular damage in patients, which in turn increases the risk of thrombosis after flap grafting.
1.6 Number of venous anastomoses
Lee et al.[21] a 2016 study retrospectively analysed patients with anterior femoral episcleral flap repair after oral cancer resection and found that although anastomosis of two veins took an average of approximately 30 minutes longer to operate than anastomosis of only one vein, the incidence of vascular crisis and venous vascular occlusion was significantly lower. According to the multifactorial analysis of this study, the number of venous anastomoses greater than one was a protective factor for the development of the vascular crisis. Some investigators suggest that anastomosis of two veins results in better flap return than one vein. If a patient has an obstruction of one vein, the other vein can continue to return venous blood, and two veins result in more efficient blood flow, reducing the risk of flap bruising and improving flap survival[22]. This reduces the risk of flap stasis and improves flap survival.
2. Impact of unbalanced data
The cohort data for this study exemplify data imbalance, with significant differences in the number of minority classes (n = 46) and majority classes (n = 524). Models constructed based on imbalanced data cannot learn the typical characteristics of the minority class in full detail, resulting in predictive models developed using imbalanced data that often perform poorly when applied to new datasets. These models are often "overfitted", and overfitted models tend to underestimate the probability of events in low-risk patients and overestimate the probability of events in high-risk patients, which may influence clinical decision making[23]. SMOTE is an oversampling technique that creates artificial samples based on actual samples in the dataset, but not identical, theoretically reducing the overfitting of the model[24]. Since data imbalance can adversely affect the performance of predictive models, we improved the distribution of majority versus minority classes by using the SMOTE method to fit the model using the sampled training data making the model learn as much as possible about the pattern of occurrence of vascular crises.
3.Significance of each model factor
Integrating the order of importance of the variables of each model and the univariate analysis showed that the occurrence of free flap graft vascular crisis is a multifactor-driven adverse outcome. As seen in the variable importance rankings, the top 5 risk factors in the three models were roughly similar, with the main difference being that the models differed in the proportion of each predictor. We can find that time to surgery and fibrin content ranked high in importance in the three models, which corroborates with the risk factors identified by multifactorial logistic regression. Although some of the top-ranked factors were not consistent with the risk factors identified by multifactorial logistic regression, such as platelet count and BMI. Other studies reported risk factors including BMI, ischemic time, and platelet count[4, 25]. For patients with excessive BMI, Sinha, S. et al[25]suggested that adequate discretion should be exercised when performing free flap grafting in obese patients. In addition, prolonged ischemia time of free flaps and subsequent ischemia-reperfusion injury can increase the risk of postoperative complications and eventual flap graft failure, but this study did not include it due to too many missing values of ischemia time. Elevated platelets are a risk factor for thrombosis, and Stevens, M. N. et al. found a 2.67-fold increased risk of flap graft failure for every 1-unit rise in platelet count in patients with head and neck surgical free flap grafts, which is consistent with the findings of Kalmar, C. L. et al. who studied the association of thoracic microvascular repair failure with platelet counts in women[26, 27].
3. Neural network model has better predictive efficacy for free flap crises
For previous studies of the free flap graft crisis, most multifactorial aspects were analysed using traditional logistic regression-based methods[28, 29] or decision tree algorithms to study flap graft failure without using neural network algorithms[30]. It should be noted that neural network algorithms are more adaptive than machine learning algorithms such as logistic regression, decision trees, and support vector machines, and are capable of successive training when a large number of samples are updated, and their “black box” nature makes them more accessible for clinical staff to master[31]. These algorithms’ “black box” makes them more accessible for clinical staff to master. In our study, the accuracy, sensitivity and specificity of the neural network model were 0.781, 0.857 and 0.773 respectively, with an AUC of 0.828 which shows that it has good recognition of whether vascular crisis occurs in postoperative patients and a certain degree of accuracy in predicting whether vascular crisis occurs in the future. Accuracy. We found a high accuracy (0.855) and specificity (0.884) to predict the occurrence of vascular crisis in free flaps using the random-sum model. This indicates that the random forest model can determine the non-occurrence of crisis. Still, its sensitivity is 0.571 and it does not yet have a high accuracy in determining the ability of patients to develop vascular crisis. The AUC value of the random forest model was 0.730 and the combined sensitivity and specificity showed that the model had some ability to identify the occurrence of vascular crisis in free flap grafts. The validity of the tree model constructed in this study was not significantly different from the results of predictive models demonstrated in other studies. As Shi YC et al.[30] developed three machine learning models to predict microvascular reconstruction failure with AUC values ranging from 0.7 to 0.77, and O'Neill et al.[32] used a random forest model to predict the occurrence of flap graft failure in breast microvascular reconstruction patients to obtain an AUC of 0.67 for the test set. The AUC (0.775) of the logistic regression was close to that of the random forest model, but there was a gap in prediction accuracy between the two.
4. Summary
Free flap grafting is a well-established technique for trauma repair, and timely identification and recognition of those at risk of postoperative complications can help improve the success rate of flap grafting[33]. Therefore, this study predicts the occurrence of a vascular crisis in postoperative patients by building a risk model for the vascular crisis in free flap transplantation to detect the vascular crisis as early as possible and provide timely treatment to improve the success rate of flap transplantation. Machine learning methods are now widely used in disease prediction, aided diagnosis, and prognosis and have broad prospects. In this study, a commonly used machine learning algorithm was selected to construct a risk prediction model for the occurrence of vascular crisis after free flap grafting, which has an excellent predictive effect and a clinical reference value. This study is a single-centre retrospective study. Although the model achieved a high degree of discrimination, relatively few factors were included and limited cases were collected. The model needed to learn the complete pattern of the clinic’s free flaps of vascular crisis. Future multicenter and large-sample studies are needed to optimise and validate the model’s applicability.