Use of serum soluble ST2 in the manufacture of a prognostic product for patients with aortic dissection, and related predictive devices

Abstract

The present invention relates to the use of serum soluble ST2 in the manufacture of a prognosis prediction product for patients with aortic dissection, and a related prediction device. The serum soluble ST2 level in patients with aortic dissection is quantified using an ELISA method. Serum soluble ST2 can be used as a predictive indicator of preoperative perfusion injury and in-hospital adverse events in patients with aortic dissection, and can be used to manufacture a product that predicts or assists in the prediction of prognosis in patients with aortic dissection. Patients with aortic dissection who have low serum soluble ST2 levels have a better prognosis than those with high serum soluble ST2 levels. This can improve the risk prediction ability for MAEs in patients with aortic dissection based on known risk factors, accurately stratify patient risk in clinical settings, and improve patient survival rates.

Description

[Technical Field]

[0001] The present invention is in the field of diagnostics, and specifically relates to the use of serum soluble ST2 in the manufacture of prognostic products for patients with aortic dissection, and related prognostic devices. [Background technology]

[0002] Aortic dissection (AD) is a potentially fatal clinical emergency with an untreated mortality rate of approximately 1%–2% per hour after onset. The European Society of Cardiology's clinical guidelines recommend that patients with type A AD (grade I and grade B) undergo emergency surgery. However, even with surgical treatment, the in-hospital mortality rate for patients with Stanford type A aortic dissection (AAD) and coronary hypoperfusion or severe coronary artery disease remains above 50%. Therefore, prognostic information for patients who undergo surgery is crucial for guiding clinical prevention strategies.

[0003] Over the past several decades, perfusion impairment has been recognized as a strong predictor of poor outcomes in surgical patients with acute type A AD. While assessment of perfusion impairment typically requires computed tomography and magnetic resonance imaging (MRI), these techniques are not routinely used in clinical practice due to their complexity, inconsistency in individual application, and unavailability of key data. Furthermore, extensive research has been conducted on prognostic markers for aortic dissection. Although fibrin-related markers (D-Dimer), inflammation-related markers (C-reactive protein), and cardiovascular biomarkers (NT-proBNP or cardiac troponin) have been shown to be associated with clinical outcomes in AD patients, none of these has been recommended as prognostic biomarkers for AD in clinical guidelines.

[0004] ST2 is a receptor for interleukin-33 (IL-33), and includes soluble ST2 receptors (sST2) and membrane-bound functional receptors (ST2L). In the event of mechanical overload, sST2 is secreted into the circulation as a "decoy" receptor for IL-33, and inhibits the cardioprotective mechanism of the IL33 / ST2 axis by competitively binding with IL-33. Summary of the Invention

[0005] The technical problem that the present invention aims to solve is how to manufacture a product that predicts the prognosis of patients with aortic dissection and / or how to obtain a marker that predicts the prognosis of patients with aortic dissection.

[0006] In order to solve the above technical problems, the present invention provides the use of a soluble ST2 (sST2) level measurement system in the manufacture of a product for predicting or aiding in the prediction of the prognosis of a patient with aortic dissection, or in predicting or aiding in the prediction of the prognosis of a patient with aortic dissection.

[0007] In the above uses, the system may be a product, which may include reagents, kits, and / or equipment necessary for measuring soluble ST2 levels.

[0008] In the above-mentioned use, the product may include a reagent, kit, and / or device necessary for measuring the soluble ST2 level, which may be the serum soluble ST2 level of aortic dissection patients to be measured.

[0009] In the above uses, the reagent may comprise a substance for measuring soluble ST2 levels by enzyme immunoassay, immunofluorescence, radioimmunoassay, co-immunoprecipitation, immunoblotting, high performance liquid chromatography, capillary gel electrophoresis, near-infrared spectroscopy, mass spectrometry, immunochemiluminescence, colloidal gold immunoassay, fluorescence immunochromatography, surface plasmon resonance, immuno-PCR, or biotin-avidin.

[0010] In the above use, the reagent may contain soluble ST2 (as a quantitative standard) or may contain soluble ST2 (as a quantitative standard) and an antibody that specifically binds to soluble ST2.

[0011] In the above use, the kit may be an enzyme immunoassay kit.

[0012] In the above uses, the prognosis may be whether a patient with aortic dissection experiences preoperative organ perfusion disorders and / or in-hospital adverse events.

[0013] Preoperative organ perfusion impairment can be assessed based on CT images, clinical characteristics, and biomarker levels in patients with aortic dissection. Organ perfusion impairment may include at least one of the following: 1) Coronary artery perfusion disorder: Ischemic electrocardiogram changes, elevated troponin levels, and regional wall motion abnormalities on echocardiogram. 2) Liver perfusion disorder: Elevated aspartate aminotransferase (>45U / L), elevated alanine aminotransferase (>60U / L). 3) Mesenteric perfusion disorder: abdominal pain, tenderness on palpation (painful symptoms, chief complaint), elevated lactate levels (>2.25 mmol / L). 4) Renal perfusion disorder: creatinine (>111 μmol / L), blood urea nitrogen (>18 mg / dl). 5) Nervous system perfusion disorder: transient ischemic attack, limb ischemia (pulselessness, clinical symptoms of limb ischemia, elevated creatine kinase level). Organ perfusion disorder may be the presence of at least one of the above organ perfusion disorders.

[0014] In-hospital adverse events may include MAEs, defined as the need for rethoracotomy and / or the development of postoperative acute heart failure, renal failure, respiratory distress syndrome, neurological ischemic injury, sepsis, or death.

[0015] To solve the above technical problems, the present invention further provides a device for predicting or assisting in prediction of the prognosis of a patient with aortic dissection. The device may include a data receiving module and a data processing module. The data receiving module is configured to receive the serum soluble ST2 level of the patient with aortic dissection to be measured. The data processing module converts the soluble ST2 level from the data receiving module into a risk value for the prognosis of the patient with aortic dissection to be measured, and the data processing module is used to predict the prognosis of the patient with aortic dissection to be measured based on the risk value.

[0016] In the above device, the prognosis may be whether or not a patient with aortic dissection experiences preoperative organ perfusion disorders and / or in-hospital adverse events.

[0017] Preoperative organ perfusion impairment can be assessed based on CT images, clinical characteristics, and biomarker levels in patients with aortic dissection. Organ perfusion impairment may include at least one of the following: 1) Coronary artery perfusion disorder: Ischemic electrocardiogram changes, elevated troponin levels, and regional wall motion abnormalities on echocardiogram. 2) Liver perfusion disorder: Elevated aspartate aminotransferase (>45U / L), elevated alanine aminotransferase (>60U / L). 3) Mesenteric perfusion disorder: abdominal pain, tenderness on palpation (painful symptoms, chief complaint), elevated lactate levels (>2.25 mmol / L). 4) Renal perfusion disorder: creatinine (>111 μmol / L), blood urea nitrogen (>18 mg / dl). 5) Nervous system perfusion disorder: transient ischemic attack, limb ischemia (pulselessness, clinical symptoms of limb ischemia, elevated creatine kinase level). Organ perfusion disorder may be the presence of at least one of the above organ perfusion disorders.

[0018] In-hospital adverse events may include MAEs, defined as the need for rethoracotomy and / or the development of postoperative acute heart failure, renal failure, respiratory distress syndrome, neurological ischemic injury, sepsis, or death.

[0019] The risk value for soluble ST2 (sST2) may be 84.6 ng / mL. Patients with aortic dissection whose serum sST2 level is greater than 84.6 ng / mL have a higher risk of in-hospital adverse events than patients with aortic dissection whose serum sST2 level is less than 84.6 ng / mL. Patients with aortic dissection whose serum sST2 level is less than 84.6 ng / mL have a better prognosis than patients with aortic dissection whose serum sST2 level is greater than 84.6 ng / mL. The patient with aortic dissection may be Chinese.

[0020] In order to solve the above technical problems, the present invention further provides the use of serum soluble ST2 as a biomarker in the manufacture of a product for measuring the prognosis of patients with aortic dissection, or in measuring the prognosis of patients with aortic dissection.

[0021] In the above use, the prognosis may be whether or not a patient with aortic dissection will experience preoperative organ perfusion disorders and / or in-hospital adverse events. The product may be a reagent, a kit, and / or a device.

[0022] In the above uses, the reagent may comprise a substance for measuring soluble ST2 levels by enzyme immunoassay, immunofluorescence, radioimmunoassay, co-immunoprecipitation, immunoblotting, high performance liquid chromatography, capillary gel electrophoresis, near-infrared spectroscopy, mass spectrometry, immunochemiluminescence, colloidal gold immunoassay, fluorescence immunochromatography, surface plasmon resonance, immuno-PCR, or biotin-avidin.

[0023] In the above use, the reagent may contain soluble ST2 (as a quantitative standard) or may contain soluble ST2 (as a quantitative standard) and an antibody that specifically binds to soluble ST2.

[0024] In the above use, the kit may be an enzyme immunoassay kit.

[0025] In order to solve the above technical problems, the present invention further provides a computer-readable storage medium for predicting or assisting in predicting the prognosis of a patient with aortic dissection. The computer-readable storage medium can cause a computer to perform the following steps: The serum soluble ST2 level of the subject aortic dissection patient is measured, and this level is converted into a prognosis risk value for the subject aortic dissection patient, and the prognosis of the subject aortic dissection patient is predicted based on the risk value.

[0026] In the computer-readable storage medium, the prognosis may be whether or not the patient with aortic dissection experiences preoperative organ perfusion disorders and / or in-hospital adverse events.

[0027] Preoperative organ perfusion impairment can be assessed based on CT images, clinical characteristics, and biomarker levels in patients with aortic dissection. Organ perfusion impairment may include at least one of the following: 1) Coronary artery perfusion disorder: Ischemic electrocardiogram changes, elevated troponin levels, and regional wall motion abnormalities on echocardiogram. 2) Liver perfusion disorder: Elevated aspartate aminotransferase (>45U / L), elevated alanine aminotransferase (>60U / L). 3) Mesenteric perfusion disorder: abdominal pain, tenderness on palpation (painful symptoms, chief complaint), elevated lactate levels (>2.25 mmol / L). 4) Renal perfusion disorder: creatinine (>111 μmol / L), blood urea nitrogen (>18 mg / dl). 5) Nervous system perfusion disorder: transient ischemic attack, limb ischemia (pulselessness, clinical symptoms of limb ischemia, elevated creatine kinase level). Organ perfusion disorder may be the presence of at least one of the above organ perfusion disorders.

[0028] In-hospital adverse events may include MAEs, defined as the need for rethoracotomy and / or the development of postoperative acute heart failure, renal failure, respiratory distress syndrome, neurological ischemic injury, sepsis, or death.

[0029] To solve the above technical problems, the present invention further provides a method for predicting the prognosis of a patient with aortic dissection, which comprises the steps of measuring the serum soluble ST2 (sST2) level of a patient with aortic dissection to be measured, converting the level into a risk value for the prognosis of the patient with aortic dissection to be measured, and predicting the prognosis of the patient with aortic dissection to be measured based on the risk value.

[0030] Specifically, patients with aortic dissection whose serum sST2 levels exceed 84.6 ng / mL are at or are expected to be at higher risk of in-hospital adverse events than patients with aortic dissection whose serum sST2 levels are less than 84.6 ng / mL. Patients with aortic dissection whose serum sST2 levels are less than 84.6 ng / mL are at or are expected to have a better prognosis than patients with aortic dissection whose serum sST2 levels are greater than 84.6 ng / mL.

[0031] In the above method, the prognosis may be whether or not the patient with aortic dissection experiences preoperative organ perfusion disorders and / or in-hospital adverse events.

[0032] Preoperative organ perfusion impairment can be assessed based on CT images, clinical characteristics, and biomarker levels in patients with aortic dissection. Organ perfusion impairment may include at least one of the following: 1) Coronary artery perfusion disorder: Ischemic electrocardiogram changes, elevated troponin levels, and regional wall motion abnormalities on echocardiogram. 2) Liver perfusion disorder: Elevated aspartate aminotransferase (>45U / L), elevated alanine aminotransferase (>60U / L). 3) Mesenteric perfusion disorder: abdominal pain, tenderness on palpation (painful symptoms, chief complaint), elevated lactate levels (>2.25 mmol / L). 4) Renal perfusion disorder: creatinine (>111 μmol / L), blood urea nitrogen (>18 mg / dl). 5) Nervous system perfusion disorder: transient ischemic attack, limb ischemia (pulselessness, clinical symptoms of limb ischemia, elevated creatine kinase level). Organ perfusion disorder may be the presence of at least one of the above organ perfusion disorders.

[0033] In-hospital adverse events may include MAEs, defined as the need for rethoracotomy and / or the development of postoperative acute heart failure, renal failure, respiratory distress syndrome, neurological ischemic injury, sepsis, or death.

[0034] In the above-mentioned method, the serum soluble ST2 level of the subject patient with aortic dissection can be measured using a reagent, kit, and / or device necessary for measuring the soluble ST2 level.

[0035] In the above method, the reagent may include a substance that measures soluble ST2 levels by enzyme immunoassay, immunofluorescence, radioimmunoassay, co-immunoprecipitation, immunoblotting, high performance liquid chromatography, capillary gel electrophoresis, near-infrared spectroscopy, mass spectrometry, immunochemiluminescence, colloidal gold immunoassay, fluorescence immunochromatography, surface plasmon resonance, immuno-PCR, or biotin-avidin.

[0036] In the above method, the reagent may include soluble ST2 (as a quantitative standard), or may include soluble ST2 (as a quantitative standard) and an antibody that specifically binds to soluble ST2.

[0037] In the above method, the kit may be an enzyme immunoassay kit.

[0038] To solve the above technical problems, the present invention further provides a product for predicting the prognosis of patients with aortic dissection, which includes reagents, kits, and / or equipment necessary for measuring soluble ST2 levels.

[0039] In the above product, the reagent may include a substance for measuring soluble ST2 levels by enzyme immunoassay, immunofluorescence, radioimmunoassay, co-immunoprecipitation, immunoblotting, high performance liquid chromatography, capillary gel electrophoresis, near-infrared spectroscopy, mass spectrometry, immunochemiluminescence, colloidal gold immunoassay, fluorescence immunochromatography, surface plasmon resonance, immuno-PCR, or biotin-avidin.

[0040] In the above product, the reagent may include soluble ST2 (as a quantitative standard) or may include soluble ST2 (as a quantitative standard) and an antibody that specifically binds to soluble ST2.

[0041] In the above product, the kit may be an enzyme immunoassay kit.

[0042] The product may consist of the reagents, kits, and / or equipment necessary for measuring soluble ST2 levels, along with other substances used in measuring soluble ST2 levels, or it may consist of only the reagents, kits, and / or equipment necessary for measuring soluble ST2 levels.

[0043] In the above product, the soluble ST2 level may be a serum soluble ST2 level.

[0044] In the above product, the prognosis may be whether or not the patient with aortic dissection experiences preoperative organ perfusion disorders and / or in-hospital adverse events.

[0045] The aortic dissection patient may be a Stanford type A aortic dissection patient. The patient may be a Chinese population.

[0046] The use or method may be a non-disease diagnostic use or method, or a disease diagnostic use or method. The use or method may not be directly aimed at obtaining a disease diagnostic result or health status in a living human or animal, or may be directly aimed at obtaining a disease diagnostic result or health status in a living human or animal.

[0047] The use or method may be a non-therapeutic use or method, or a therapeutic use or method for a disease. The use or method may not be directly aimed at restoring or gaining health or alleviating pain in a living human or animal, or may be directly aimed at restoring or gaining health or alleviating pain in a living human or animal.

[0048] The present invention will be described in detail below with reference to specific embodiments, but the examples shown are for the purpose of illustrating the present invention and do not limit the scope of the present invention. The examples provided below can be used as a guide for those skilled in the art to make further improvements, but do not limit the present invention in any way. [Brief explanation of the drawings]

[0049] [Figure 1] Related information for patients in the exploratory cohort and validation cohort. A is related information for patients in the validation cohort, and B is related information for patients in the exploratory cohort. [Figure 2] Comparison of serum sST2 levels in patients with aortic dissection (with or without perfusion disorder) in the exploratory cohort. The vertical axis represents serum sST2 levels (ng / mL). [Figure 3] Serum sST2 levels in patients with aortic dissection (with or without perfusion impairment) in the exploratory cohort. [Figure 4] This is a correlation analysis between serum sST2 levels and the number of organs with perfusion disorders in patients with aortic dissection with perfusion disorders in an exploratory cohort. [Figure 5] Comparison of serum sST2 levels between patients in the MAEs and non-MAEs groups of the exploratory cohort. [Figure 6] This is a comparison of serum sST2 levels between patients in the MAEs and non-MAEs groups of the exploratory cohort. The vertical axis represents serum sST2 levels (ng / mL). [Figure 7] Comparison of serum sST2 levels between patients in the MAEs and non-MAEs groups in the validation cohort. [Figure 8]Comparison of serum sST2 levels between patients in the MAEs and non-MAEs groups in the validation cohort. The vertical axis represents serum sST2 levels (ng / mL). [Figure 9] This study compares the ability of various logistic regression models to assess the risk of MAEs using sST2 levels. [Figure 10] Figure 1 shows the receiver operating characteristic curve of sST2 in distinguishing patients with MAEs from those without MAEs in the validation cohort. The area under the curve is 0.75. DETAILED DESCRIPTION OF THE INVENTION

[0050] Unless otherwise specified, the experimental methods used in the following examples are all conventional methods. Materials, reagents, instruments, etc. used in the following examples are all commercially available unless otherwise specified. Quantitative experiments in the following examples were all performed three times, and the average values ​​were used as the results.

[0051] Relevant definitions in the present embodiment are as follows:

[0052] In-hospital adverse events (MAEs) were defined as the need for rethoracotomy and / or the development of postoperative acute heart failure, renal failure, respiratory distress syndrome, neurological ischemic injury, sepsis, or death.

[0053] Organ perfusion disorders: Preoperative perfusion disorders are assessed based on CT images, clinical characteristics, and biomarker levels. Multiorgan perfusion disorders are characterized by at least one of the following: 1) Coronary perfusion disorders: ischemic electrocardiogram changes, elevated troponin levels, and regional wall motion abnormalities on echocardiogram. 2) Liver perfusion disorders: elevated aspartate aminotransferase (>45 U / L) and alanine aminotransferase (>60 U / L). 3) Mesenteric perfusion disorders: abdominal pain, tenderness on palpation (painful symptoms, chief complaint), elevated lactate (>2.25 mmol / L). 4) Renal perfusion disorders: creatinine (>111 μmol / L) and blood urea nitrogen (>18 mg / dL). 5) Nervous system perfusion disorders: transient ischemic attack, limb ischemia (pulselessness, clinical symptoms of limb ischemia, elevated creatinine kinase levels). Organ perfusion disorder is the presence of at least one organ perfusion disorder.

[0054] The experimental protocol in the present example was approved by the Hospital Ethics Committee of Beijing Anzhen Hospital Affiliated to Capital Medical University, and the study was conducted in accordance with the principles of the Declaration of Helsinki. Prior to participation, each patient from Beijing Anzhen Hospital Affiliated to Capital Medical University or their legal representative signed a written informed consent.

[0055] Example 1: Correlation between serum sST2 expression levels and preoperative perfusion injury in patients with aortic dissection Following the principles of gender and age matching, 46 patients with aortic dissection with and without perfusion impairment were selected as an exploratory cohort to measure the prognosis of patients with aortic dissection. The serum levels of soluble receptor for interleukin-33 (IL-33) (sST2) were measured using ELISA and analyzed for correlation with preoperative perfusion impairment. Perfusion impairment is defined as the presence of at least one organ perfusion disorder. The mean age of the 92 patients was 47.2 years, and 78 (84.8%) were men. Perfusion impairment and specific MAEs are shown in Figure 1.

[0056] 1. Measurement of serum sST2 levels Kit: Human ST2 / IL-33R DuoSet Catalog number: DY523B-05 Company:R&D

[0057] Procedure for measuring serum sST2 by ELISA: 1) The capture antibody was diluted to its working concentration in PBS without carrier protein. 100 μL of diluted capture antibody (provided in the kit) was added to each well, the plate was sealed, and incubated overnight at room temperature. 2) Aspirate the solution from each well and wash with wash buffer. Repeat twice more for a total of three washes. After the final wash, invert the plate to absorb any remaining wash buffer onto a clean paper towel. 3) 300 μL of Reagent Diluent (included in the kit) was added to each well and incubated at room temperature for at least 1 hour. 4) Repeat the aspiration and washing of step 2). 5) 100 μL of sample or standard solution (included in the kit) was added to each well, sealed with adhesive tape, and incubated at room temperature for 2 hours. 6) Repeat the aspiration / wash procedure from step 2) of the plate preparation. 7) Add 100 μL of detection antibody (included in the kit) to each well, diluted with reagent diluent, seal with new film, and incubate at room temperature for 2 hours. 8) Repeat the aspiration / wash of step 2) of plate preparation. 9) 100 μL of the diluted Streptavidin-HRP solution was added to each well, which was then sealed with film and incubated at room temperature for 20 minutes. The plate was kept out of direct sunlight. 10) Repeat the aspiration and washing of step 2). 11) Add 100 μL of substrate solution (included in the kit) to each well and incubate at room temperature for 20 minutes. Avoid exposing the plate to direct sunlight. 12) 50 μL of reaction stop solution was added to each well and the plate was gently tapped to mix thoroughly. 13)OD 450nm The optical density of each well was immediately measured using a microplate reader set at .

[0058] 2. Analysis of measurement results In the exploratory cohort, imaging and clinical test indicators determined that there were 46 patients with aortic dissection accompanied by perfusion impairment. After gender and age matching, 46 patients without perfusion impairment were screened. The results of sST2 level measurements are shown in Figures 2 and 1. Serum sST2 levels were significantly increased in patients with perfusion impairment (represented by the group with perfusion impairment in Figures 2 and 3) compared with patients with aortic dissection without perfusion impairment (represented by the group without perfusion impairment in Figures 2 and 3). The results in Figure 3 show that the median sST2 level in the aortic dissection group without perfusion impairment was 30.7 ng / mL, with the first and third quartiles being 13.8 ng / mL and 48.0 ng / mL, respectively. The median sST2 level in the perfusion impairment group was 60.8 ng / mL, with the first and third quartiles being 36.8 ng / mL and 125.5 ng / mL, respectively. A t-test analysis showed that sST2 expression levels in patients with perfusion impairment were significantly increased compared with those in patients without perfusion impairment (P < 0.001). The correlation between sST2 and the number of perfusion-impaired organs was analyzed by Spearman's method, and the results are shown in Figure 4. The Spearman correlation coefficient was 0.515 (P < 0.001), indicating that sST2 was strongly correlated with the number of perfusion-impaired organs, i.e., the greater the number of perfusion-impaired organs, the higher the sST2 level.

[0059] Example 2: Prognostic value of serum sST2 expression level in patients with aortic dissection in in-hospital MAES 1. Comparison of sST2 expression levels between patients with MAEs and those without MAEs Of the 92 patients with aortic dissection in the exploratory cohort, the patients with aortic dissection in Example 1 were divided into an MAE group (29 patients) and a non-MAE group (63 patients) based on the occurrence of MAEs (death, heart failure, etc.) during their current hospitalization, and serum sST2 levels were measured in the patients using the same ELISA experimental method as in Example 1. Here, MAEs are in-hospital adverse events and are defined as the need for rethoracotomy and / or the occurrence of postoperative acute heart failure, renal failure, respiratory distress syndrome, neurological ischemic injury, sepsis, or death.

[0060] The statistical results show the following: Comparisons of sST2 levels in blood samples by group are shown in Figures 5 and 6. The median sST2 level in patients in the non-MAEs group was 31.1 ng / mL, with the first and third quartiles being 16.1 ng / mL and 60.2 ng / mL, respectively. The median sST2 level in patients in the MAEs group was 54.2 ng / mL, with the first and third quartiles being 40.5 ng / mL and 112.8 ng / mL, respectively. Compared with the non-MAEs group, the sST2 expression level in patients in the MAEs group was significantly increased (P < 0.001).

[0061] 2. Logistic regression analysis of the relationship between sST2 levels and MAEs A total of 155 patients with aortic dissection (newly enrolled patients, different from the 92 patients in Example 1) were selected as the validation cohort. A total of 50 patients experienced cardiovascular adverse events (e.g., death, heart failure) during hospitalization. The mean age of the 155 patients was 48.9 years, and 121 (78.1%) were men. The validation cohort of patients with aortic dissection was divided into a MAEs group (50 patients) and a non-MAEs group (105 patients). Serum sST2 levels were measured using the same ELISA method as in Example 1. The difference in serum sST2 levels between the MAEs and non-MAEs groups was examined. The results are shown in Figures 7 and 8. The median sST2 level in the non-MAEs group was 39.9 ng / mL, with the first and third quartiles being 21.5 ng / mL and 80.9 ng / mL, respectively. The median sST2 level in patients with MAEs was 98.5 ng / mL, with the first and third quartiles at 48.7 ng / mL and 148.3 ng / mL, respectively. The serum sST2 levels in patients with MAEs (represented as the event group in Figure 8) in the validation cohort were significantly higher than those in the non-MAEs group (represented as the non-event group in Figure 8, P < 0.001), consistent with the results of the exploratory cohort. Specifically, patients with aortic dissection with high serum sST2 levels had a higher risk of in-hospital adverse events than patients with low serum sST2 levels, and patients with aortic dissection with low serum sST2 levels had a better prognosis than patients with high serum sST2 levels.

[0062] To evaluate the value of sST2 on MAEs in patients with aortic dissection, we constructed three logistic regression models based on known risk factors for aortic dissection, including age, sex, coronary artery disease, diabetes, hyperlipidemia, hypertension, sudden pain, electrocardiogram abnormalities, pulse deficits, renal failure, and hypotension / shock / tamponade. In Model 1, sST2 was used as the independent variable and MAEs as the dependent variable, and the risk assessment ability of sST2 on MAEs was analyzed without adjusting for known risk factors. In Model 2, sST2 was also used as the independent variable and MAEs as the dependent variable, and the independent risk assessment ability of sST2 on MAEs was evaluated after adjusting for patient characteristics, including known risk factors for patient characteristics, such as sex, age, coronary artery disease, diabetes, hyperlipidemia, and hypertension. In Model 3, based on Model 2, adjustments were made for known risk factors in the patient's basic characteristics as well as risk factors in the patient's onset characteristics (sudden onset pain, ECG abnormalities, pulse deficits, renal failure, hypotension / shock / tamponade, etc.), and the independent risk assessment ability of sST2 for MAEs after adjustment for the patient's basic characteristics and onset characteristics was evaluated.

[0063] We constructed three logistic regression models as follows: Model 1: No adjustment was made for any factors. Model 2: Adjusted for sex, age, coronary artery disease, diabetes, hyperlipidemia, and hypertension. Model 3: Adjusted for age, sex, coronary artery disease, diabetes, hyperlipidemia, hypertension, sudden pain, electrocardiogram abnormalities, pulse defects, renal failure, and hypotension / shock / tamponade.

[0064] The analysis results of various logistic regression models are shown in Figure 9. Without adjustment for any factors (Model 1), the odds ratio for sST2 and MAEs risk was 3.28 (95% CI: 1.99–5.39, P < 0.001). After adjusting for patient sex, age, coronary artery disease, diabetes, hyperlipidemia, and hypertension (Model 2), the odds ratio for sST2 and MAEs risk was 3.59 (95% CI: 2.04–6.34, P < 0.001). After adjusting for patient sex, age, coronary artery disease, diabetes, hyperlipidemia, hypertension, sudden pain, ECG abnormalities, pulse defects, renal failure, and hypotension / shock / tamponade (Model 3), the odds ratio for sST2 and MAEs risk was 3.44 (95% CI: 1.94–6.11, P < 0.001). These results demonstrate that sST2 has the ability to assess MAE risk and can independently predict MAE risk even after adjusting for known risk factors. Finally, using a receiver operating characteristic curve (ROC), the critical value (risk value) of sST2 in the validation cohort was determined to be 84.6 ng / mL, with an area under the curve of 0.75 (Figure 10). This effectively distinguishes patients with MAE from those without MAE. Specifically, patients with aortic dissection whose serum sST2 levels exceeded 84.6 ng / mL were at higher risk of in-hospital adverse events than those with serum sST2 levels below 84.6 ng / mL, and patients with aortic dissection whose serum sST2 levels below 84.6 ng / mL had a better prognosis than those with aortic dissection whose serum sST2 levels exceeded 84.6 ng / mL. All of the patients were Chinese.

[0065] Currently, clinical assessment of in-hospital MAEs in patients with aortic dissection is primarily based on patient characteristics and onset characteristics. However, despite interventional treatment, the mortality rate in patients with aortic dissection remains very high. This is because, in addition to aortic rupture, impaired organ perfusion is the most important cause of death. However, there are currently no effective indicators for evaluating patient prognosis, particularly post-onset organ perfusion. This invention proposes that sST2, a simple and easily measured indicator, can be used to assess impaired organ perfusion in patients with aortic dissection. This improves the ability to predict the risk of MAEs in patients with aortic dissection based on known risk factors, allowing for accurate patient risk stratification and thereby improving patient survival in clinical practice. [Industrial Applicability]

[0066] The present invention was developed with the aim of guiding clinical prevention strategies for patients with aortic dissection. By measuring the expression level of sST2 in patients with aortic dissection, it was found that sST2, a marker involved in the occurrence and progression of aortic dissection, can be used to indicate preoperative perfusion disorder and is independently associated with the occurrence of in-hospital adverse events in type A AD patients undergoing surgery.

[0067] Based on previous clinical findings, we investigated the correlation between serum sST2 levels and aortic dissection with multiple organ perfusion disorders and prognosis. We used an ELISA method to quantify serum soluble ST2 levels in 247 patients with Stanford type A aortic dissection (AAD) who underwent surgical treatment. The statistical results demonstrated that soluble ST2 is a useful predictor of preoperative perfusion disorders in AD patients and that sST2 can more effectively identify AAD patients who will experience in-hospital adverse events than conventional clinical evaluation indicators.

[0068] The present invention uses ELISA to quantify serum soluble ST2 levels in patients with aortic dissection. It has been discovered that serum soluble ST2 is a useful predictor of preoperative perfusion injury in these patients and can be used to manufacture products that predict or assist in the prediction of prognosis in these patients. Measuring serum soluble ST2 levels can predict the prognosis of patients with aortic dissection, and patients with low serum sST2 levels have a better prognosis than those with high serum sST2 levels. The present invention improves the ability to predict the risk of MAEs in patients with aortic dissection based on known risk factors, enabling accurate risk stratification in clinical settings and improving patient survival.

Claims

1. Use of a soluble ST2 level measurement system in the manufacture of a product for predicting or aiding in the prediction of prognosis in patients with aortic dissection, or in predicting or aiding in the prediction of prognosis in patients with aortic dissection.

2. 2. The use according to claim 1, characterized in that the product comprises reagents, kits and / or equipment necessary for measuring the soluble ST2 level.

3. The use according to claim 1 or 2, characterized in that the prognosis is whether the patient with aortic dissection will experience preoperative organ perfusion disorders and / or in-hospital adverse events.

4. A device for predicting or assisting in predicting the prognosis of a patient with aortic dissection, The device includes a data receiving module and a data processing module, wherein the data receiving module is arranged to receive the serum soluble ST2 level of the aortic dissection patient to be measured, and the data processing module converts the soluble ST2 level from the data receiving module into a risk value of prognosis of the aortic dissection patient to be measured, and the risk value is used to predict the prognosis of the aortic dissection patient to be measured.

5. The device of claim 4, wherein the prognosis is whether the aortic dissection patient will experience preoperative organ perfusion disorders and / or in-hospital adverse events.

6. Use of serum soluble ST2 as a biomarker in the manufacture of a product for determining the prognosis of patients with aortic dissection, or in determining the prognosis of patients with aortic dissection.

7. The use according to claim 6, wherein the prognosis is whether the patient with aortic dissection will experience preoperative organ perfusion disorders and / or in-hospital adverse events.

8. 8. The use according to claim 6 or 7, characterized in that the product is a reagent, a kit and / or an apparatus.

9. A computer-readable storage medium for predicting or assisting in predicting the prognosis of a patient with aortic dissection, comprising: The computer-readable storage medium is characterized in that it causes a computer to execute steps of measuring the serum soluble ST2 level of a patient with aortic dissection to be measured, converting the level into a risk value for prognosis of the patient with aortic dissection to be measured, and predicting the prognosis of the patient with aortic dissection to be measured based on the risk value.

10. 10. The computer-readable storage medium of claim 9, wherein the prognosis is whether the aortic dissection patient will experience preoperative organ perfusion disorders and / or in-hospital adverse events.

11. A method for predicting the prognosis of a patient with aortic dissection, comprising: A method comprising the steps of measuring the serum soluble ST2 level of a patient with aortic dissection to be measured, converting the level into a risk value for prognosis of the patient with aortic dissection to be measured, and predicting the prognosis of the patient with aortic dissection to be measured based on the risk value.

12. 12. The method of claim 11, wherein the prognosis is whether the aortic dissection patient will experience preoperative organ perfusion disorders and / or in-hospital adverse events.

13. The method according to claim 11 or 12, characterized in that measuring the serum soluble ST2 level of the subject aortic dissection patient is performed using reagents, kits, and / or equipment necessary for measuring the soluble ST2 level.

14. A product for predicting the prognosis of a patient with aortic dissection, comprising reagents, kits, and / or equipment necessary for measuring soluble ST2 levels.

15. 15. The product of claim 14, wherein the prognosis is whether the aortic dissection patient will experience preoperative organ perfusion disorders and / or in-hospital adverse events.

Images