Use of neutrophils and / or total bilirubin in predicting early risk of bleeding after endoscopic biliary stent placement

Abstract

The application provides application of a substance for detecting neutrophil and / or total bilirubin level in preparation of a kit for predicting early postoperative hemorrhage risk after endoscopic biliary stent implantation, and provides a related prediction model. The application firstly verifies that the substance for detecting neutrophil and / or total bilirubin level can be used for predicting early postoperative hemorrhage risk after endoscopic biliary stent implantation, and based on this, provides a related prediction model, the model has good discrimination ability, and can provide a valuable evaluation tool for preventing hemorrhage of a patient subjected to endoscopic biliary stent implantation.

Description

Technical Field

[0001] This invention relates to the field of biodetection technology, specifically to the application of substances for detecting neutrophil and / or total bilirubin levels in the preparation of kits for predicting the risk of early bleeding after endoscopic biliary stent placement. Background Technology

[0002] Common bile duct stones are the most common cause of biliary obstruction, and serious complications include cholangitis. Acute cholangitis is a life-threatening disease caused by an increase in bacterial infection of the biliary tree. Endoscopic treatment is the recognized first-line treatment for acute cholangitis. Endoscopic retrograde cholangiopancreatography (ERCP) with biliary stent placement is widely used in the treatment of common bile duct stones and has become the gold standard for palliative care of malignant biliary obstruction.

[0003] Complications following endoscopic biliary stent placement, such as postoperative pancreatitis, perforation, and hemorrhage, have attracted considerable attention from researchers. Postoperative hemorrhage is one of the most serious complications, with an incidence rate as high as 27%. Current research shows a decrease in postoperative mortality but an increase in postoperative hemorrhage. Previous studies have identified exogenous factors such as pre-resection and endoscopic sphincterotomy as risk factors for postoperative hemorrhage after ERCP. A previous study also indicated that visible bleeding during the procedure is a potential risk factor. However, few studies have focused on endogenous factors, which are also a significant cause of postoperative hemorrhage. To date, however, the etiology and risk factors remain poorly understood.

[0004] Postoperative hemoglobin (Hb) decrease is an objective parameter of blood loss during ERCP, and its correlation with actual blood loss is better than subjective estimation. Studies have shown that an early decrease in Hb is indeed a marker of the likelihood of serious injury, and a decrease in Hb levels usually indicates a poor postoperative prognosis. The degree of postoperative Hb decrease is an independent risk factor for postoperative complications.

[0005] Therefore, there is an urgent need for novel biomarkers to predict Hb decline in order to improve clinical outcomes after ERCP and reduce mortality in critically ill patients. This invention aims to explore the decline in Hb levels after ERCP, elucidate possible factors associated with Hb decline, and ultimately design a predictive model to provide a valuable assessment tool for preventing bleeding in patients undergoing endoscopic biliary stent placement. Summary of the Invention

[0006] To overcome the deficiencies in the prior art, this invention provides the application of substances for detecting neutrophil and / or total bilirubin levels in the preparation of kits for predicting the risk of early bleeding after endoscopic biliary stent placement, and provides related prediction models.

[0007] To achieve the above objectives, the present invention adopts the following technical solution:

[0008] A first aspect of the invention is to provide the use of substances for detecting neutrophil and / or total bilirubin levels in the preparation of a kit for predicting the risk of early bleeding after endoscopic biliary stent placement.

[0009] Furthermore, the above-mentioned neutrophil and / or total bilirubin levels refer to the neutrophil and / or total bilirubin levels in patients with common bile duct stones prior to endoscopic biliary stent placement.

[0010] A second aspect of the present invention is to provide a risk prediction system for early bleeding after endoscopic biliary stent placement, comprising:

[0011] One acquisition module is used to acquire the neutrophil and / or total bilirubin levels of patients with common bile duct stones before endoscopic biliary stent placement.

[0012] A calculation module, connected to the acquisition module mentioned above, establishes a nomogram of the probability of early bleeding after endoscopic biliary stent placement in patients with common bile duct stones based on the following Logistic regression model. Two factors correspond to different risk score ranges, and the total risk score is calculated accordingly. The vertical value corresponding to the total risk score represents the probability of early bleeding.

[0013] P = 0.039 * neutrophil percentage + 0.007 * total bilirubin - 4.109;

[0014] An output module, connected to the calculation module, is used to output the predicted probability of early bleeding after endoscopic biliary stent placement in patients with common bile duct stones.

[0015] Furthermore, the system also includes an analysis module connected to the acquisition and output modules, used to analyze the relationship between neutrophil and / or total bilirubin levels and bleeding risk; based on a set threshold for neutrophil and / or total bilirubin levels, the system assesses the patient's high postoperative bleeding risk, and then displays the risk level by the output module.

[0016] Furthermore, if the thresholds for the above analysis module are neutrophils >84.2% and / or total bilirubin >45.35, then the risk of early bleeding after endoscopic biliary stent placement is greater in patients with common bile duct stones.

[0017] Furthermore, the aforementioned computing module and analysis module are respectively a computer host, a central processing unit, or a network server.

[0018] Furthermore, the aforementioned output module can be a display, printer, or audio output device.

[0019] Furthermore, the connection between the acquisition module and the calculation / analysis module is a wired connection and / or a wireless connection.

[0020] A third aspect of the present invention is to provide a risk prediction kit for early bleeding after endoscopic biliary stent placement, comprising:

[0021] Substances used to detect neutrophil and / or total bilirubin levels in patients with common bile duct stones before endoscopic biliary stent placement; and

[0022] Product instruction manual.

[0023] Furthermore, the aforementioned product instructions instruct the establishment of a nomogram of the probability of early bleeding after endoscopic biliary stent placement in patients with common bile duct stones based on the following Logistic regression model. Two factors correspond to different risk score ranges, and the total risk score is calculated accordingly. The vertical value corresponding to the total risk score represents the probability of early bleeding.

[0024] P = 0.039 * neutrophil percentage + 0.007 * total bilirubin - 4.109.

[0025] The present invention adopts the above technical solution and has the following technical effects compared with the prior art:

[0026] This invention is the first to verify that substances that detect neutrophil and / or total bilirubin levels can be used to predict the risk of early bleeding after endoscopic biliary stent placement, and provides a related predictive model based on this. This model has good discriminative ability and can provide a valuable assessment tool for preventing bleeding in patients undergoing endoscopic biliary stent placement. Attached Figure Description

[0027] Figure 1 This is a nomogram of the risk of early bleeding after endoscopic biliary stent placement in a patient with common bile duct stones, according to one embodiment of the present invention.

[0028] Figure 2 This is the receiver operating curve for a logistic regression model to predict the risk of early bleeding after endoscopic biliary stent placement in patients with common bile duct stones. Detailed Implementation

[0029] The present invention will now be described in detail with reference to specific embodiments and accompanying drawings to enable a better understanding of the invention. However, the following embodiments do not limit the scope of the invention.

[0030] Unless otherwise specified, the methods used in the embodiments are conventional methods, and the reagents used are commercially available reagents or reagents prepared according to conventional methods, unless otherwise specified.

[0031] Example 1

[0032] This study included 150 patients who underwent ERCP biliary stent placement at the Department of General Surgery, Yangpu Hospital Affiliated to Tongji University, between January 2018 and January 2020. All included patients were inpatients, and discharged patients were followed up by telephone and clinically for one year. The inclusion criteria were as follows: (1) patients aged >18 years; (2) patients who voluntarily signed the ERCP treatment informed consent form. The exclusion criteria were as follows: (1) patients with serious underlying diseases, such as malignant tumors, renal failure, cirrhosis, etc., which may affect blood biochemical indicators; (2) patients with incomplete medical records; (3) patients lost to follow-up. Patient characteristics are shown in Table 1 below.

[0033] Table 1. Demographic and clinical characteristics of 150 patients

[0034]

[0035]

[0036] WBC (white blood cells); Hb (hemoglobin); CRP (C-reactive protein); TBIL (total bilirubin); ALT (alanine aminotransferase); AST (aspartate aminotransferase); ALP (alkaline phosphatase); PT (prothrombin time); DD (D-dimer).

[0037] Biliary stent placement was performed using a standard duodenoscope (Olympus Medical Systems, PA, USA). Two types of biliary stents were used (8.5F, 9cm; primarily 7F, 14cm).

[0038] Endoscopic retrograde cholangiopancreatography (ERCP) procedure

[0039] The procedure was performed by two experienced endoscopists who perform this surgery on over 200 patients annually. Preoperative analgesia (meperidine) and sedation (diazepam) were administered. The average procedure time was approximately 30 minutes. Successful placement of a biliary stent and reconstruction of the bile drainage pathway were the criteria for successful ERCP. Following ERCP, patients were kept NPO (nothing by mouth) and given intravenous fluid support. Routine blood samples were taken at 6 and 24 hours post-ERCP to measure biochemical parameters and amylase and lipase activities. All patients were monitored for at least 48 hours to prevent potential ERCP-related acute complications.

[0040] Observation indicators

[0041] Observational indicators included age, sex, indications, ERCP-related procedures, laboratory tests, imaging findings, ERCP outcomes, and postoperative adverse events. Complete blood count and blood biochemical parameters were collected before and 24 hours after ERCP. A postoperative decrease in hemoglobin of 10 g / L was considered significant.

[0042] Statistical analysis

[0043] Data were obtained by reviewing relevant medical records, laboratory tests, endoscopy reports, and other relevant examination results from the hospital's medical system. SPSS version 25.0 (IBM Corp., NY, USA) and R software (version 4.0.2) were used for analysis. Variable compatibility was assessed using the Shapiro-Wilk test. Patient characteristics were expressed using descriptive statistics. Parameters conforming to a normal distribution were expressed as mean ± standard deviation, while parameters not conforming to a normal distribution were expressed as median and distribution (25th-75th percentile). Parameter comparisons were performed using the chi-square test. The Mann-Whitney U test was used to compare the differences in parameters before and after surgery; all parameters were non-normally distributed. Univariate and multivariate logistic regression analyses were used to test the relationship between predictors of variables and postoperative Hb decrease. The nomogram was calibrated by plotting the probabilities of observed outcomes. Receiver operating characteristic (ROC) curves were used to describe and compare the accuracy of hematological ratios. The ROC curve is a graphical representation of sensitivity (x-axis) versus 1-specificity (y-axis). The area under the curve (AUC) represents the accuracy of the marker in distinguishing between the risk of decreased hemoglobin and normal levels. The cutoff value for each biomarker was calculated using the Youden index. A p-value < 0.05 was considered statistically significant.

[0044] result

[0045] As shown in Table 2 below, ERCP patients who underwent biliary stent placement showed significantly lower white blood cell count (P=0.006), neutrophil percentage (P=0.009), TBIL level (P<0.001), alanine aminotransferase (P<0.001), and aspartate aminotransferase (P<0.001).

[0046] Table 2 Comparison of laboratory test results after ERCP biliary stent placement

[0047]

[0048] WBC (white blood cells); CRP (C-reactive protein); TBIL (total bilirubin); ALT (alanine aminotransferase); AST (aspartate aminotransferase).

[0049] Although no bleeding was observed during follow-up, Hb levels decreased early postoperatively (P<0.001), indicating a risk of bleeding. Univariate logistic regression analysis showed that early postoperative Hb decrease was positively correlated with neutrophil percentage (P=0.001), alkaline phosphatase (P=0.025), TBIL (P=0.004), ALT (P=0.039), and AST (P=0.008) levels. Furthermore, we performed multivariate logistic regression analysis, including univariate risk factors; multivariate logistic regression analysis showed that only neutrophil percentage (OR=1.039, 95% CI=1.005–1.075, P=0.025) and TBIL level (OR=1.007, 95% CI=1.001–1.014, P=0.020) were significant risk factors for early Hb decrease (Table 3). Based on the results of multivariate analysis, the predictive formula for the probability of bleeding after ERCP is: P = 0.039 * neutrophil percentage + 0.007 * TBIL - 4.109.

[0050] Table 3. Univariate and multivariate analyses of risk factors for early Hb decline after ERCP biliary stent placement.

[0051]

[0052]

[0053] WBC (white blood cells); CRP (C-reactive protein); TBIL (total bilirubin); ALT (alanine aminotransferase); AST (aspartate aminotransferase); ALP (alkaline phosphatase); PT (prothrombin time); DD (D-dimer).

[0054] To predict biliary drainage bleeding after endoscopic stent placement, neutrophil percentage and TBIL were included in the nomogram. Figure 1 The nomogram for predicting bleeding is calculated by summing the scores of each blood test variable to obtain a total score. The predicted risk corresponding to the total score is the risk of biliary drainage bleeding after endoscopic stent placement.

[0055] ROC analysis using a logistic regression model was performed to determine its clinical differential value. Figure 2As shown, the neutrophil percentage (AUC = 0.655) and TBIL level (AUC = 0.668) are the most accurate indicators for identifying bleeding risk. A neutrophil percentage >84.2% is considered a predictor of bleeding risk, with a cutoff sensitivity of 68.9% and a specificity of 61.7%. Using total bilirubin >45.35 μmol / L as a predictor of bleeding risk, the cutoff value has a sensitivity of 66.7% and a specificity of 61.7%. ROC analysis results show that the model has an AUC of 0.702 (0.617-0.811) and a cutoff point of 0.546, demonstrating good discriminative ability.

[0056] The specific embodiments of the present invention have been described in detail above, but they are only examples, and the present invention is not limited to the specific embodiments described above. For those skilled in the art, any equivalent modifications and substitutions to the present invention are also within the scope of the present invention. Therefore, all equivalent changes and modifications made without departing from the spirit and scope of the present invention should be covered within the scope of the present invention.

Claims

1. Application of substances for detecting neutrophil and / or total bilirubin levels in the preparation of kits for predicting the risk of early bleeding after endoscopic biliary stent placement.

2. The application according to claim 1, characterized in that, The neutrophil and / or total bilirubin levels refer to the neutrophil and / or total bilirubin levels in patients with common bile duct stones prior to endoscopic biliary stent placement.

3. A risk prediction system for early bleeding after endoscopic biliary stent placement, characterized in that, include: One acquisition module is used to acquire the neutrophil and total bilirubin levels of patients with common bile duct stones before endoscopic biliary stent placement. A calculation module, connected to the acquisition module, establishes a nomogram of the probability of early bleeding after endoscopic biliary stent placement in patients with common bile duct stones based on the following Logistic regression model. Two factors correspond to different risk score ranges, and the total risk score is calculated accordingly. The value vertically corresponding to the total risk score represents the probability of early bleeding. P = 0.039 * neutrophil percentage + 0.007 * total bilirubin - 4.109; An output module, connected to the calculation module, is used to output the predicted probability of early bleeding after endoscopic biliary stent placement in patients with common bile duct stones.

4. The risk prediction system according to claim 3, characterized in that, It also includes an analysis module connected to the acquisition module and the output module, used to analyze the relationship between neutrophil and total bilirubin levels and bleeding risk; based on the set thresholds for neutrophil and total bilirubin levels, it evaluates that the patient has a high risk of postoperative bleeding, and then the risk level is output and displayed by the output module.

5. The risk prediction system according to claim 4, characterized in that, The thresholds for the analysis module are neutrophils >84.2% and total bilirubin >45.

35. The higher the risk of early bleeding after endoscopic biliary stent placement in patients with common bile duct stones, the greater the risk.

6. The risk prediction system according to claim 4, characterized in that, The computing module and the analysis module are respectively a computer host, a central processing unit, or a network server.

7. The risk prediction system according to claim 3, characterized in that, The output module is a display, printer, or audio output device.

8. The risk prediction system according to claim 3, characterized in that, The acquisition module is connected to the calculation / analysis module via wired connection and / or wireless connection.

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